1- CHO Chemistry …………………………………………..

2- Lipids Chemistry ………………………………..…….. 18

3- Ptn Chemistry ………………………………………….. 36

4- Enzymes …………………………………………………... 59

5- CHO Metabolism ……………………….…………….. 73

6- Lipid metabolism ……………………………….…….. 113

7- Ptn Metabolism ……………………………………….. 140

8- Vitamins ……………………………………………….….. 172

❖ Definition: - are organic substances composed of carbon, hydrogen, and oxygen.
Or - are simple sugar (polyhydroxy aldehyde or ketone) or its derivatives.
‫ السكر البسيط وأي من مشتقاته‬:‫ه‬ ‫الكربوهيدرات ي‬
‫ األلدهيدات أو الكيتونات عديدة الهيدروكسيل‬:‫السكر البسيط هو‬

❖ Classification of carbohydrates: according to the hydrolysis )‫ )تحلل مائي‬products

Contain 1 sugar unit. (Can’t be Hydrolyzed)

1. Monosaccharides
Contain 2 sugar units.
2. Disaccharides
Contain 3-10 sugar units.
3. Oligosaccharide
Contain more than 10 sugar units.
4. Polysaccharides

N.B. Usually the ratio between Carbon & H2O is 1. Hence the name carbohydrate.

Monosaccharides (glycoses)
❖ Definition: They are the simplest units of carbohydrate containing one sugar unit.
General formula is: Cn(H2O)n.
❖ Naming of monosaccharides:
A. According to the Functional group:
1. Aldoses: monosaccharides containing aldehyde group (-CHO).
2. Ketoses: monosaccharides containing ketone group (-C=O).
B. According to the No. of Carbon atoms:

Sugar No. of Carbons Includes

Trioses 3 Aldotrioses and ketotrioses
Tetroses 4 Aldotetroses and ketotetroses
Pentoses 5 Aldopentoses and ketopentoses
Hexoses 6 Aldohexoses and ketohexoses

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❖ Classification of monosaccharides:
1. Trioses: monosaccharides containing 3 carbons.
a. Aldotrioses: Glyceraldehyde “glycerose”.
b. Ketotrioses: Dihydroxyacetone.

2. Tetroses: monosaccharides containing 4 carbon atoms:

a. Note: The suffix —ulose means Keto group.

3. Pentoses: monosaccharides containing 5 carbon atoms.

a. Aldopentoses: Ribose, arabinose, xylose and lyxose.
b. Ketopentoses: Ribulose and xylulose.

c. Importance (functions) of pentoses:

▪ Ribose:
- Enter in the structure of nucleic acids (RNA and DNA.)
- Enters in the structure of ATP, GTP .
- Enters in the structure of coenzymes NAD, NADP and FAD.

4. Hexoses: monosaccharides containing 6 carbon atoms.

a. Aldohexoses: glucose, mannose, and galactose.
b. Ketohexose: fructose.

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 c. Importance (functions) of Hexoses:
1- Glucose: “grape sugar” is the most important sugar of carbohydrate:
- Glucose is the main sugar in blood
- Glucose is one of major sources of energy in the body.
- In the liver and other tissues, glucose is converted to all carbohydrates in the
body e.g. glycogen, galactose,
2- Galactose:
- It can be converted into glucose in the liver.
- It is synthesized in mammary gland to make the lactose of milk (milk sugar)
3- Fructose: “fruit sugar”:
- It can be converted into glucose in the liver.
- It is the main sugar of semen.
4- Mannose: A constituent of many glycoproteins.

❖ Properties of monosaccharides:
▪ Ring (cyclic) structure of sugars:
a) This Cyclic form is due to: reaction between C=O (carbonyl) of aldehyde group in
Aldoses or of Ketol group in Ketoses with an alcoholic hydroxyl group to form
• Furanose → 4 Carbon ring
• Pyranose → 5 Carbon ring
b) If the remaining —OH is on the right side, it is α— sugar.
If the remaining —OH is on the left side, it is β — sugar.
c) Pyranose and furanose:
- The 1-5 ring form is called pyranose as it resembles an
Organic compound called pyran e.g. α and β glucopyranose.
- The 1-4 ring form is called furanose as it resembles an
Organic compound called furan e.g. α and β glucofuranose.

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 d) Haworth and chair forms:
i. Cyclic structure of sugars may be present in the form of Haworth or chair forms. as
follows:
▪ All the -OH groups on the right side in old ring structure are written downwards
in Haworth formula.
▪ All the -OH groups on the left side in old ring structure are written upwards in
Haworth formula.
▪ These rules are reversed at CH2-OH groups e.g. last carbon atom of glucose that
attached to oxygen i.e. c4 in furanose and C5 in pyranose.

Asymmetric carbon atom:

Is the carbon atom to which 4 different groups or atoms are attached.

Any substance containing asymmetric carbon atom shows 2 Properties,

Optical activity and Optical isomerism.
a. Optical activity: It is the ability of substance to rotate plane polarized light either to the
right or to the left.
1- If the substance rotates plane polarized light to the right so it is called:
dextrorotatory or d or (+).
2- If it rotates it to the left so it is called: levorotatory or I or (-).
3- Glucose contains 4 asymmetric carbon atoms. It is dextrorotatory, so it is
sometimes named dextrose.
4- Fructose contains 3 asymmetric carbon atoms. It is levorotatory. so it is sometimes
called: LevuIose

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 b. Optical isomerism: It is the ability of substance to present in more than one form
(isomer).
- Substance containing one asymmetric carbon atom has 2 isomers.
1- Configuration (Enantiomers): ‫األخية‬ ‫ر‬ ‫الل قبل‬
‫الزم كل الكربونات تكون معكوسة وابص ع ي‬
a. The simplest carbohydrate is Glyceraldehyde that has one asymmetric carbon atom.
So it has 2 optically active forms.

2- Anomeric carbons & anomers: ring structure ‫الزم السكر يكون يف ال‬
a. Anomeric carbon: is the asymmetric carbon atom obtained from active carbonyl
sugar group: C1 in aldoses and C2 in ke toses.
b. Anomers: These are isomers obtained from the change of position of hydroxyl
group attached to the anomeric carbon e.g. α and β glucose are 2 anomers.
Also α and β fructose are 2 anomers.

3- Aldose-Ketose isomerism (functional group isomerism): Have the same molecular

formula but differs in functional group.
EX: Fructose & glucose One contains Ketone group (C=O) and the other contains
aldehyde group (-CHO). Both are isomers.
4- Epimers: ‫الل مختلفة‬
‫ه ي‬ ‫كربونه واحده بس ي‬
A. Epimers are isomers having more than asymmetric carbon, all are same
except only one is different.
a. Glucose & Mannose are epimers at carbons 2.
b. Glucose & Galactose are epimers at carbons 4.

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 MCQs
1. Which of the following is a ketose?
A) Galactose B) Fructose C) Fucose
D) Mannose E) Xylose
2. Glucose is:
A) Source of energy B) Not reducing sugar C) Ketohexose
D) Not optically active E) Pentosugar.
3. The (D & L) configuration of a sugar is based on its analogy to:
A) D-Glucose B) α D-glucose C) D-Fructose
D) D-Ribose E) D-Glyceraldehyde
4. For a compound to be optically active it must be:
A) Colored B) A protein C) Symmetric
D) Asymmetric E) Plant in nature
5. If you dissolve pure crystals of glucose in water and leave the solution for equilibrium,
the solution will contain:
A) α-Glucose only B) β-Glucose only
C) Open chain glucose only E) A mixture of a, β and open chain glucose
6. Glucose and galactose are epimers. This means that:
A) They are mirror images of each other.
B) One is pyranose and the other is furanose.
C) They rotate plane polarized light in opposite directions.
D) They differ only in the configuration about carbon atom number 2.
E) They differ only in the configuration about carbon atom number 4.
7. The reference sugar is:
A) Glucose B) Fructose C) Mannose
D) Ribulose E) Glyceraldehyde
8. Rotation of the plane of polarized light is caused by solutions of all of the following
monosaccharides, Except:
(a) Glucose (b) Glyceraldehyde (c) Fructose
(d) Dihydroxyacetone (e) None of the above
9. Ribulose is an example of:
(a) Aldopentose (b) Ketohexose (c) Ketopentose
(d) Deoxy sugar (e) Sugar alcohol
10. A pair of Sugars differing from each other in configuration around the functional group
is called:
a- Anomers. b- Epimers. c- Racemers. d- Stereoisomers.
11. D-glucose and D-fructose
a- Epimers at C2 b- Epimers at C4 c- Anomers d. Aldose-ketose isomers.
12. Which of the following are Aldohexoses?
a- Ribose, fructose and erythrose. b- Fructose, ribose, and ribulose.
c- Lactose, sucrose, and maltose. d- Glucose, mannose, and galactose.

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 Sugar derivatives
1- Sugar acids:
- Are produced by oxidation of carbonyl carbon, last carbon or both.
Carbonyl carbon Aldonic acid e.g. glucose gluconic acid.
Last hydroxyl carbon uronic acid Glucose glucuronic acid
BOTH Aldaric acids Glucose glucaric
(saccharic) acid

- L-Ascorbic acid (vitamin C) is an important sugar acid.

2- Sugar alcohols:
- Are produced by Reduction of carbonyl carbon
sugar Sugar alcohols function
Glucose sorbitol
Mannose Mannitol
galactose Dulcitol
Glyceraldehyde glycerol Structure of Triacylglecerol
dihydroxyacetone (TAG) &
phospholipid
Ribose ribitol Structure of riboflavin
(vitamin B2 )
Inositol Myoinositol Structure of phospholipid
Cyclic alcohol It acts as precursor of 2nd
messenger
Fructose mannitol and
sorbitol

3- Deoxysugars:
1. Are produced by replacement of hydroxyl groups by
hydrogen atom i.e. one oxygen is missed.
2. Occurring in nucleic acid DNA Ribose De-oxy ribose.
3. L-Fucose (6-deoxyL-galactose): enters in BL.group AG.

4- Amino sugars: in these sugars, the hydroxyl group attached to C2 is replaced by an amino or
an acetyl-amino group.
1) Amino sugars enter in glycoproteins.
2) Examples:
a) Glucosamine: It enters in heparin and hyaluronic acid.

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 b) Galactosamine: It enters in chondroitin sulphate.
c) Mannosamine: It enters in neuraminic and sialic acids.
5- Amino sugar acids:
1. Formed by addition of amino sugars and some acids.
2. Examples:
1- Neuraminic acid = Mannosamine + pyruvic acid. 9C
2- Sialic acid or N-acetylneuraminic acid (NANA) enters in glycolipid.
6- Glycosidic bond and glycosides:
A. Glycosidic bond: It is the bond between a carbohydrate and another Compound to form
a complex carbohydrate.
1. This bond is between the hydroxyl group of anomeric carbon of monosaccharide and
another compound which may be:
a) Another monosaccharide to form disaccharide.
b) A glycone i.e. non-carbohydrate to form glycoside.
2. N and O-glycoside bond:
B. Examples of gilycosides:
1. Disaccharides: discussed later.
2. Sugar nucleotide as ATP, GTP and other nucleotides: aglycone here is purines And
pyrimidines.
5. Cardiac glycosides:
a) Aglycone here is steroid.
b) Cardiac glycosides such as digitalis.
C) used in treatment of cardiac disease.
MCQs
13. All the following are sugar alcohols, EXCEPT:
a- Galactitol b- Mannitol c- Xylulose d- Sorbitol

14. Ribitol is:

a. Deoxysugar b- Sugar alcohol c- Amino sugar d- Sugar acid

15. Sorbitol is produced by reduction of:

a- Glucose or fructose b- Glucose or galactose
c- Glucose or mannose d- Galactose or fructose

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 DISACCHARIDES
• The most important disaccharides are:
▪ {α-glucose + α-glucose} : → α (1-1) glycosidic bond → trehalose
→ α (1-4) glycosidic bond → Maltose
→ α (1-6) glycosidic bond → Isomaltose
▪ { α-glucose + β-fructose} : → (α1-β2) glycosidic bond or (β2-1 fructosidic b) → Sucrose
▪ {β-glucose + β-galactose} : → β (1-4) galactosidic bond → Lactose
• Properties: all disaccharide except (trehalose & Sucrose) showing the following characters :
• It is a reducing agent (can reduce Benedict’s reagent).
• It can be present in α and β forms.
• It can form characteristic osazone crystals.

Sugar Source

Maltose a) Malt.
b) Maltose is produced during digestion of starch by
amylase enzyme.
Isomaltose Isomaltose is produced during digestion of starch
and glycogen by amylase enzyme

Lactose a) Milk.

- Non-fermentable sugar.
Sucrose a) cane and beet sugar (table sugar)

b) Pineapple and carrot.

• invert Sugar :
▪ Structure: It is a sugar that contains equal number of both glucose and fructose
molecules (unbound).
▪ Sources: a) Bee honey
b) By hydrolysis of sucrose by sucrase (invertase) enzyme
▪ Properties: levorotatory sugar due to strong levorotatory of fructose invert the previous
dextro-rotatory action of sucrose.

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 MCQs
16. The sugar found in milk is:
a- Galactose b- Glucose. c- Fructose. d- Lactose.

17. The glycosidic linkage seen in sucrose is:

a- Alpha linkage b- Beta 1-4 linkage
c- Alpha 1-6 linkage d- Alpha 1-2 linkage

18. All the followings have glycosidic bond, EXCEPT:

a- Maltose. b- Sucrose. c- N-acetyl glucosamine. d- Inulin
19. Sucrose consists of:
a- α Glucose + β glucose b- α Glucose + β fructose
c- α Glucose + β galactose d- α Glucose + β mannose

20. Which is a non-reducing sugar?

a- Maltose b- Sucrose c- Lactose d- Isomaltose

21. The glycosidic linkage seen in lactose is:

a- Alpha 1-4 linkage b- Beta 1-4 linkage c- Alpha 1-6 linkage d- Alpha 1-2 linkage

22. The glycosidic linkage seen in maltose is:

a- Alpha 1-4 linkage b- Beta 1-4 linkage
c- Alpha 1-6 linkage d- Alpha 1-2 linkage

23. Hydrolysis of maltose will give rise to:

a. Glucose only b- Glucose and fructose
c- Glucose and galactose d- Glucose and mannose

24. Lactose by hydrolysis gives:

a- 2 glucose molecules b- Glucose and mannose.
c- Fructose and galactose. d- Glucose and galactose.

25. An invert sugar is:

a- An equimolar mixture of glucose and fructose
b- An equimolar mixture of a-glucose and Il-glucose
c- An equimolar mixture of a-fructose and ß-fructose
d- The sugar Which changes its optical activity from levorotatory to dextrorotatory.

26. Osazone formation, mutarotation and reducing property are all based on the presence
of:
a- Presence of α form b- Presence of β form
c- Presence of free carbonyl group d- Presence of cyclic structure form

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 POLYSACCHARIDES
- Thy are polymer of more than 10 unit of monosaccharides or their derivatives e.g.
(aminosugar and uronic acid).

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 HOMOPOLYSACCHARIDES
Starch Starch granule is formed of: - cereals, potatoes, 1) Starch gives blue color
1) Inner layer: called amylose. It legumes and with iodine.
constitutes 15-20% of the granule other vegetables Amylopectin gives red
and formed of non-branching color with iodine.
- In plants it
heIical structure of glucose units
synthesized by 2) Partial hydrolysis
linked together by α 1 — 4
photosynthesis. (digestion) by amylase
glycosidic bond.
enzyme gives various
2) Outer layer: called amylopectin
forms of dextrins
constitutes 80-85% of the granule
and formed of branched chain.
G Each chain is composed of 24-30
glucose units linked together by α
L
1 — 4 glycosidic bond and a 1 — 6
U glycosidic bond at branching
points.
C
Dextrins - amyIodextrin, erythrodextrin and - By hydrolysis of - They give red color with
A
achrodextrin. starch. iodine.
N
Glycogen - Highly branched chain - The storage form - gives reddish violet
S - Each branch is composed of 12-14 of CHO in human color with iodine
glucose units. and animals
- Similar to amylopectin - in liver, muscles

Cellulose - long linear chains of (β-D- - plants: vegetables, - give NO color with
glucopyranose) linked together by cotton iodine - insoluble in
β 1-4 glycosidic bond water
- The presence of cellulose in diet - Cannot be digested due
is important because it: to absence of digestive
- increases the bulk of stool. hydrolase enzyme that
- This stimulates intestinal attacks β-linkage.
movement
and prevents constipation.

Fruc Inulin - Repeated units of fructose linked - Root of artichokes - Inulin clearance is one
together by β1-2 bonds. and other plants. of diagnostic tests for
tans
investigation of GFR.

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 Heteropolysaccharides
• Glycosaminoglycans, GAGs (mucopolysaccharide):
Introduction:
1. They are formed of repeating disaccharide units (Acidic sugar- Amino sugar)n
a-The acidic sugar is either D-glucuronic acid or its epimer, L-induronic acid.
b-Amino sugar is either D-glucosamine or D-Galactosamine in which the amino group is
usually acetylated. The amino sugar may also be sulfated at carbon 4 or 6.
2. GAGs often contain sulfate group. The uronic acid and sulfate residues cause them to be
very negatively charged.
3. They are unbranched and contain no N-acetyl neuraminic acid.
4. Most of GAGs are present extracellularly except heparin.
5. Most of them form the structural components of connective tissue such as bone, elastin
and collagen.
6. They act as Lubricants and cushion for other tissues because they have the property of
holding large quantities of water.
7. When a solution of glycosaminoglycans is compressed, the water is “squeezed out” and the
glycosaminoglycans are forced to occupy a smaller volume, when the compression is
released, the glycosaminoglycans return to their original hydrated volume because of the
repulsion of their negative charges. This property is the cause of resilience of synovial fluid
and the vitreous humor of the eye.

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 Type Structure Site Functions
Hyaluronic Glucuronic acid Cartilage lubricant in joints
acid Synovial fluid makes cartilage
compressible
N-acetyl glucosamine Connective tissue cell migration during
NO Sulfate wound repair
Vitreous humor of the cell migration during
eye morphogenesis
Chondroitin Glucuronic acid sage, tendons, ligaments Have role in
4- and bones compressibility of
and 6 cartilage in weight
sulfate bearing
N-acetylgalactosamine with Aorta, skin, cornea, it binds collagen and
sulfate on either C4 or C6 umblical cord and in hold fibers in strong
certain neurons network
Keratan Galactose (no uronic acid), with Cornea corneal transparency
sulfate sulfate on C6
N-acetyl glucosamine with Found in Cartilage
sulfate on C6
Dramatan L-lnduronic acid Cornea corneal transparency
suIfate N-acetylgalactosamine with Sclera. Maintaining the shape
sulfate on C6 Skin, blood vessels and of the eye.
heart valves
Heparin lnduronic acid with sulfate on mast cells (intracellular anticoagulant
C2 compound) in the wall of
Glucosamine with sulfate on blood vessels
C2 and C6
Heparan cell membrane - act as receptors
sulfate - cell adhesion and cell-
cell interaction

basement membrane of Determining the

the kidney charge selectiveness
of glomerular
filtration.

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 Glycoproteins proteogIycans
Definition Are proteins that contain chains of glycosaminoglycans
oligosaccharide chains. attached to protein molecule
1- Structure Oligosaccharide units. Glycosaminoglycans.
CHO component
Ptn component Protein core Protein
Types of sugar Contain no uronic acid Contain uronic acid
Pentoses: as arabinose and Sugaramines as
xylose. glucosamines.
Methylpentoses: L-fucose
Sulfate group Contain no sulfate Contain sulfate.
Size of CHO component 2-15 units. More than 50 units.
Repeating structure Little or non. Repeating disaccharides.
Shape Usually branched Linear, unbranched.
2- Function - Extracellular matrix. - ground substance and support
- Mucin. tissues as cartilage, bone and
- Blood group antigens e.g. tendons
A, B and AB. - cell membrane
- Cell receptors.
- Glycophorins.
- Plasma proteins.
- Some hormones.
- Enzymes.
- Antibodies.

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 MCQs
27. The heteropolysaccharide which does not Contain sulphuric acid is:
a- Keratan sulphate b- Dermatan sulphate
c- Chondroitin sulphate d Hyaluronic acid
28. All the following are glucosans EXCEPT:
a- Starch b- inulin c- Cellulose d- Glycogen
29. Amylopectin is characterized by all of the following, EXCEPT:
a- It is a branched polymer.
b- It is structure is very near to glycogen.
c- Contains a IA and a glucosidic bond.
d- Hydrolysis by amylase gives maltose and fructose.
30. Cellulose is characterized by all of the following, EXCEPT:
a- it is a glucosans
b- Linear polymer
c- Consists of β-glucose units
d- Easily digested as it contains β glucosidic bonds
31. Cellulose is not digested as:
a- It contains α-glucosidic bond. b- It contains β -galactosidic bond.
c- It contains β -glucosidic bond. d- It contains α-fructosidic bond.
32. Heparin is:
a- A disaccharide b- An oligosaccharide c- An amino sugar
d- A non-sulfated mucopolysaccharide e- A sulfated mucopolysaccharide
33. Hyaluronic acid ¡s:
a- Glycoprotein
b- Sulfated glucuronic acid
c- Repeated disaccharide formed of glucuronic acid and N-acetyl glucosamine
d- High molecular weight positively charged Homopolysaccharide

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❖ Introduction to lipids:
a. Definition: Lipids Organic compounds related to fatty acids insoluble in water but
soluble in organic solvents i.e. ether, benzene, acetone & chloroform.
b. The hydrophobic nature of lipids is due to the predominance of hydrocarbon chains (-
CH2-CH2-CH2-) in their structure.
❖ Biomedical Importance:
1. Source of energy: (Lipids have a high energy value)
2. Supply body e’:
- Fat soluble vitamins (vit. K, E, D & A).
- Essential Fatty acid (a Linolenic & Linoleic acids).
❖ Classification:

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 Simple lipids
❖ Definition: Are esters of fatty acids with various alcohols. (Ester bond = -COO-). They are
either fats or waxes.

Fatty acids: R.COOH

- Fatty acids are water-insoluble “long chain hydrocarbons”.
- They are mostly monocarboxylic i.e. having one carboxyl group at the end of the chain
(-COOH).
- They are mostly aliphatic (i.e. not branched). A few branched chain fatty acids are
present in animals and plants.
- Fatty acids may be Saturated: (no double bonds) or
Unsaturated: (containing one or more double bonds).
- Fatty acids may be Essential: cannot be synthesized in the body or
Nonessential: can be synthesized in the body.
- Fatty acids occur mainly as esters in natural fats and oils.
- Fatty acids may also present as free fatty acids (FFA) in the plasma carried on PP.
- Short chain F.A : less than 10 C , long chain F.A: more than 10 C
❖ Numbering of carbon atoms:
1. Starting from the carboxyl group:
- 1, 2, 3 system: Give COOH No. 1 then proceed to the terminal CH3.
- α, β, system: the 1st carbon following COOH is α then proceed to the terminal CH3 .
2. Starting from the terminal methyl group (omega “ω” carbon):
- The terminal methyl carbon is given ω1 then proceeds to COOH group

❖ Position of double bonds: The most commonly used systems for designating the
Position of double bonds in unsaturated fatty acids are:
(1) The delta (Δ) numbering system e.g. palmitoleic acid C 16:1 Δ9 means that this acid
contains 16 carbons (16) and one double bond (1) and the position of double bond is
between carbon number 9 and carbon number 10 starting from carboxyl carbon 1
(2) Omega (ω) system e.g. the palmitoleic acid may be written as: C 16:1 ω7 which
indicates a double bond on seventh carbon counting from the ω-carbon atom i.e.
last –CH3 carbon.
- Cis and Trans double bonds: Double bonds in naturally occurring fatty acids in
mammals are always in a Cis form (configuration) not as Trans form:
polyunsaturated acids:
a) Cis form that the groups are on the same side.
b) Trans form means that the groups are on the opposite sides.
- Trans fatty acid may be present in certain foods, during hydrogenation of oils to
manufacture margarine.

DR. Mahmoud Ettaweel

❖ Aliphatic & Branched chain fatty acids:
Almost all fatty acids present in mammalian tissues are aliphatic i.e. straight chain.
However, branched- chain fatty acids are found in nature.
A. Phytanic acid (18C):
- Some milk products contain branched chain fatty acids called Phytanic acid it contains
4 methyl groups at position 3, 7, 11 and 15 carbons.
B. Refsum’s disease:
1. It is caused by inability of oxidation of Phytanic acid this leads to its accumulation in
plasma and tissues.
2. Manifestations: nervous tissue damage in the form of blindness and deafness.
❖ Saturated & Unsaturated fatty acids
i. Saturated fatty acids
- Have no double bonds in the chain.
- Their general formula is CH3- (CH2) n -COOH where (n) equals the number of
methylene (-CH2) groups between the methyl and carboxylic groups.
- The systemic name of saturated fatty acids ends by the suffix (-anoic) e.g. palmitic
acid (16c) has systemic name hexadecanoic acid (Hexa =6, Deca =10).
- Example of the formula of some saturated fatty acids:
▪ Butyric acid (4c) = CH3- CH2- CH2- COOH
▪ Palmitic acid (16c) = CH3 - (CH2)14 - COOH
▪ Stearic acid (18c) = CH3 - (CH2)16 – COOH

Name N.O of C occurrence

Formic 1 Takes part in the metabolism of “C1” units (formate)

Acetic 2 Major end product of carbohydrate fermentation by

Propionic 3 rumen organisms.

Butyric 4 In certain fats in small amounts (especially butter).

Palmitic acid 16 Common in all animal and plant fats

Stearic acid 18
Arachidic 20 Peanut (arachis) oil

DR. Mahmoud Ettaweel

ii. Unsaturated fatty acids:
- The general formula is (Cn- H2n-1- COOH).
- The systemic name of unsaturated fatty acids ends by the suffix (-enoic) e.g.
oleic acid (18c) has systemic name octadecenoic acids.
- Unsaturated fatty acids are either monounsaturated or polyunsaturated.
❖ Monounsaturated fatty acids (monoethenoic, monoenoic) i.e. contain one double
bond e.g. palmitoleic acid (16:1 Δ9) and oleic acid (18:1 Δ9).

❖ Polyunsaturated fatty acids (essential fatty acids=polyethenoic =polyenoic fatty

acids =PUFA) Containing more than one double bond: e.g
- In polyunsaturated F.A. each 2 double bonds are separated by methylene group
(-CH2)
- PUFA are classified according to the position of the 1st double bond in relation to
ω carbon into ω3, ω6, ω7 & ω9 F.A.
▪ ω3 PUFA:
i. PUFA having the 1st double bond at carbon 3 in relation to ω carbon
ii. E.X:
1. α Linolenic acid (18:3) —> Parent FA
2. Timnodonic acid (20 : 5)
3. Cervonic acid (22 : 6)
• α Linolenic is the precursor of other members of this group in the body.
▪ ω6 PUFA:
1. Linoleic acid (18:2) —> Parent FA
2. γ Linolenic acid (18:3)
3. Arachidonic acid (20:4)

a) Linoleic (18:2 Δ9’12, ω6) and lenolenic (18:3 Δ9’12’15, ω3):

1. They are present in linseed oil.
b) Arachidonic acid (20:4 Δ5’8’11’14, ω6).
1. It is present in peanut oil
2. It is a component of phospholipids in animal.
3. It is a precursor of a group of compounds called: eicosanoids.

DR. Mahmoud Ettaweel

❖ Essential and nonessential fatty acids:
A. Nonessential fatty acids:
1. These are fatty acids which can be synthesized in the body. Thus they are not
necessary to be obtained from the diet.
2. They include all saturated and monounsaturated fatty acids as palmitoleic and oleic
acid.
3. They can be synthesized from acetyl COA (active acetate) derived from glucose
oxidation.
B. Essential fatty acids:
a) These are fatty acids that cannot be synthesized in the body. They must be
obtained from the diet.
b) They include fatty acids that contain more than one double bond
(polyunsaturated fatty acids) e.g. lenoleic, lenolenic, arachidonic acids.
c) The human body has enzyme system that can form only one double bond at the
ninth carbon atom.
Sources:
a) Vegetable oils e.g. corn oil, soya bean oil, safflower oils, sunflower, linseed oil
and cotton seed oil.
b) Fish oils: shark liver oils, which particularly contain the ω3 polyunsaturated fatty
acids.
Importance:
a) Normal growth.
b) They enter in the structure of phospholipids and cholesterol esters.
c) They enter in the structure of cell membranes and are required for the fluidity of
membrane structure.
d) They protect against atherosclerosis and coronary heart disease by decreasing
free cholesterol and LDL.

DR. Mahmoud Ettaweel

❖ Eicosanoids
A. Definition: These are cyclic compounds that derived from arachidonic acid
(eicosatetraenoic)(20 C) after cyclization of its carbons chain to form a ring.
- Hormone like molecules produced by most mammalian cells
- Active within the cell in w’ they are produced (autocrine) or on adjacent cells
(paracrine)
- Have many physiological & pathological & Pharmacological actions
B. Components of eicosanoids:
1. Prostanoids: which comprise prostaglandins, prostacycIins and thromboxanes.
a) Prostaglandins (PG)
1) PGE2: vasodilatation, relaxation of the uterus and intestine.
2) PGF2 : vasoconstriction, contraction of the uterus and intestine.
b) prostacycIins
They cause vasodilatation and inhibit platelets aggregation
c) thromboxanes
They cause platelets aggregation
2. Leukotriens (LT):
a) They are present in leucocytes, platelets and mast cells.
b) They cause chemotaxis i.e. Collection of white blood cells at the site of
inflammation (↑ vascular permeability).
❖ Properties of fatty acids:
A. Physical properties:
1. Solubility:
a) Short chain fatty acids e.g. acetic (2C), butyric (4C) and caproic (6C) are soluble
in water
b) Long chain fatty acids are insoluble in water but soluble in nonpolar fat solvents.
2. Melting point : It depends on the length of the chain of fatty acids and the degree
of unsaturation, so:
a) Short chain and unsaturated fatty acids are liquid at room temperature.
b) Long chain saturated fatty acids are solid at room temperature.
B. Chemical properties:
❖ Properties due to “COOH” group:
1. Salt formation (soap): Fatty acids form soap (salts) with alkalies as NaOH, KOH,
Ca(OH)2 : RCOOH + NaOH R.OOONa + H20
Fatty acid Sodium hydroxide Sodium salt
2. Ester formation:
a) Fatty acids form esters (R.COO.R) with alcohols:
R.COOH + R1.OH R.COOR1 + H2O
1) Esters of fatty acids with glycerol Neutral fats (Acylglycerols).
2) Esters of fatty acids with higher alcohols waxes
3. Reduction:
2H H2O 2H
Fatty acid (R-COOH) F. aldehyde (R-CHO) F. alcohol (R-CH2OH)
❖ Properties due to double bond:
2. Hydrogenation, halogenation and oxidation: These are

DR. Mahmoud Ettaweel

 Alcohols: R.OH
I. Introduction: Alcohols associated with lipids include glycerol, cholesterol and
higher alcohols (e.g. cetylalcohol, C16H33OH) usually found in the wax.
II. Glycerol: It is polyhydric alcohol containing 3 (-OH) groups:
▪ Properties:
1. Glycerol is colorless, odorless, and hygroscopic and has sweet taste.
2. It is soluble in water and alcohol insoluble in nonpolar solvents
3. It combines with one fatty acid to form monoacylglycerol, and so on
▪ Acrolein: It is an aldehyde substance with a characteristic odour.
It derives from glycerol by losing 2 water molecules.
▪ Uses of Glycerol:
1. Nitroglycerol is used as a drug for dilatation of coronary artery.
2. Glycerol enters in manufacturing of creams and lotions for dry skin
III Cholesterol: is an alcohol and derived lipids (see later)
IV. Higher alcohol: long chain contain one (-OH) group i.e. monohydric alcohols.
Simple lipids
A. They are called simple because they are formed only from alcohols and Fatty acids.
There are two classes of simple lipids (according to the type of alcohol):
acylglycerols and waxes.
- Acylglycerols are esters of one, two or three fatty acids with glycerol
B. Numbering of carbons of glycerol is either: α, β and γ or 1, 2 and 3. Notice that
carbon 1 and 3 of glycerol in Triacylglycerols are not identical when viewed in 3
dimensions. Enzymes can differentiate between the two positions.
i.Triacylglycerols (triglycerides):
• They are called neutral fat because they carry no charge.
• Body triacylglycerols:
- Location: They are stored mainly in cytoplasm of adipose tissue cells (which is
located subcutaneously and around kidney and other organs).
- Body fat is important source of energy. Each gram fat gives 9.3
- Human fat is liquid at room temperature and contains high contents of oleic acid.
• Dietary sources of triacylglycerols:
- In animals e.g. butter and lards.
- In plants e.g. Cotton seed oil, linseed oil, sesame oil and olive oil.
- Marine oils e.g. cod liver oil and shark liver oil.
• Types of triacylglycerols:
- Simple triacylglycerols: similar 3 fatty acids are attached to glycerol.
- Mixed triacylglycerols: 3 different fatty acids are attached to glycerol.

DR. Mahmoud Ettaweel

❖ properties of triacylglycerols:
A. Physical properties:
a. Solubility: All triacylglycerols are insoluble in water, soluble in fat solvents.
b. Melting point:
- Triacylglycerols rich in unsaturated F.A. are liquid at room temperature. “Oils”.
- Triacylglycerols rich in saturated F.A. are solid at room temperature “Fats”.
c. Specific gravity: It is less than one. Specific gravity of water is one Therefore,
triacylglycerols float on the surface of water.
d. Grease stain test: All Triacylglycerols give +ve grease stain test.
B. Chemical properties:
1. Hardening (Reduction):
Def: Hydrogenation of oils to form solid fat or margarine
As: USFA are converted to SEA
2. Hydrolysis of TAG:
a. Acid Hydrolysis:
Boiling TAG with acids Glycerol + 3FAs
b. Alkaline Hydrolysis (Saponification):
• Def: Hydrolysis of TAG using alkalis
• Produces: Glycerol & Soap
• Soap: Alkaline salt of FA
TAG + 3KOH Glycerol + 3RCOOK (K soap)
c. Enzymatic Hydrolysis:
TAG by lipase enzyme gives glycerol & 3 FAs
3. Rancidity:
Def: Development of toxic compound with bad flavor (odor & taste) of fats or
oils duo to oxidation of USFA.
Types: Hydrolytic & oxidative.
1. Hydrolytic Rancidity:
Cause: Due to presence of (H2O) OR Bacteria (Contain lipase enzyme).
• Lipase causes release of short chain F.As which are volatile.
2. Oxidative Rancidity:
• Oils are more liable to develop this type of rancidity why?
As: they are rich in USFA.
• Oxidation at USFA → Peroxides, ketones & aldehydes → Bad flavor
Q: Addition of vit. E, phenols & quinones may prevent oxidative rancidity why?
As: They are antioxidants so protects USFA against oxidation.
ii.Waxes
❖ Def: Esters of long chain FA with long chain alcohols contain one (-OH) group.
❖ Site: Trunks of trees & fur of animals
❖ Function: Acts as a protective coat
❖ Examples:
1. True wax (Bee’s wax): Esters of palmitic acid e’ mericyl alcohol (C30)
2. Lanolin (in hair): Esters of cholesterol derivatives
3. Vit A (Retinol) esters 4. Vit D (Calciferol) esters
❖ Properties:
1. They have the same physical properties as fat.
2. They give negative Acrolein test because they contain no glycerol.
3. They are not digested by lipase enzyme. Thus they are not utilized.
4. They are solids at room temperature.

DR. Mahmoud Ettaweel

 Triacylglycerols Waxes

Composition Contain glycerol Contain no glycerol so,

i.e. give positive Acrolein test. give negative Acrolein test.

Melting point At room temperature: they are At room temperature, they

either solids or liquids are solids.

Rancidity They may undergo rancidity. They do not undergo

rancidity.

MCQ
1. The structure of stearic acid is:
a- 16 carbon, no double bond b- 18 carbon, no double bond
c- 18 carbon, two double bonds d- 18 carbon, three double bonds
.

2. The structure of oleic acid can be described as:

a- 16 carbon, one double bond b- 18 carbon, one double bond
c- 18 carbon, two double bonds d- 18 carbon, three double bonds
.

3. The major fat in adipose tissue is:

a- Phospholipid b- Cholesterol c- Sphingolipids d- Triacylglycerol.
.

4. Which of the following is true about linoleic acid?

a- It contains 18 C atoms. b- It contains 2 double bonds.
c- Not formed inside the body. d. It is W3 FA.
.

5. A saturated F.A which contains 16 C is

a- Palmitoleic acid b. Oleic acid
c- Stearic acid d- palmitic acid.
6. All are Correct as regards a-linolenic acid, EXCEPT:
a- It is an essential FA. b- Dienoic (contains 2 double bounds)
c- It is FA d-lt contains 18 C atoms.
7. True statements about lipids include the following EXCEPT
a- They are an intracellular energy source
b-They are poorly soluble in water
c- They are structural components of membranes
d- They are composed Of only carbon, hydrogen and oxygen
8. Fatty acids that are dietary essentials in humans include Which the following:
a- Palmitic acid b-Stearic acid
c- Oleic acid d- Linoleic

DR. Mahmoud Ettaweel

 Conjugated Lipids
❖ Def: Simple lipids conjugated with another group.
❖ Classification:

Phospholipids
❖ Classified according to the alcohol present into
A. Glycerophosphatides (Phosphoglycerides): Containing (glycerol)
B. Sphingomyelin: Containing sphingosine (sphingol)
Glycerophosphatides (Phosphoglycerides)
- Phospholipids containing glycerol as alcohol
- They are derivatives of phosphatidic acid.
1. Phosphatidic acid:
• Diacylglycerol phosphate
• Formed during synthesis of TAG & phospholipid
• FA at position 1 is SFA & at position 2 USFA
• Other Phosphoglycerides are formed by conjugation of different groups to
phosphate
2. Lecithin (Phosphatidyl Choline):
• Structure: Formed of phosphatidic acid + Choline
• Functions:
- Enters in the structure of cell membrane.
- Acts as lipotropic factor. I.e. prevent fatty liver.
- Forms cholesterol ester, Cholesterol esters are transported to the liver, and
excreted with bile, This prevent atherosclerosis.
Lecithin + Cholesterol LCAT Cholesterol ester + lysolecithin
- Lecithin acts as body store of Choline. Choline is important for:
i- Nerve transmission. ii- Transmethylation: It acts as methyl donor

DR. Mahmoud Ettaweel

 - Dipalmityl lecithin (i.e. lecithin which contains 2 palmitic acid residues)
Act as a surfactant in lung
i- Dipalmityl lecithin is continuously secreted by the lung cells in the alveolar wall,
forming a monolayer over the watery surface of the alveolus and so lowers the
surface tension this helps expiration and inspiration
• During expiration, the surfactant becomes solid under pressure. This prevents
the adherence of alveolar wall.
• During inspiration, The surfactant makes the lung easier to expand.
❖ Respiratory distress syndrome (hyaline membrane disease):
• In premature babies, lungs do not secrete enough surfactant. This leads to lung
collapse and death from respiratory failure.
• Treatment of this case needs putting the premature babies in incubator and
administration of surfactant locally in the lung.
3. Phosphatidyl serine:
• Formed of phosphatidic acid + serine
4. Cephalin (Phosphatidyl ethanolamine):
• Structure: Formed of phosphatidic acid + ethanolamine
• Functions: coagulation mechanism activating factors
5. Phosphatidyl Inositol (Lipositol):
• Structure: Formed of phosphatidic acid + Inositol
• Functions: acts as precursor of 2nd messenger “IP3”
6. Plasmalogens:
• Structure: Same structure as lecithin but FA at position 1
is replaced by unsaturated fatty alcohol
• Functions: present in brain & muscles “Lipophilic
antioxidants”.
7. Cardiolipins (Diphosphatidyl glycerol):
• Structure: Formed of 2 molecules of phosphatidic acid
connected by 1 molecule of glycerol
• Hydrolytic products: 4FA + 3 Glycerol + 2 Phosphate
• Functions:
1. Cardiolipins is the major lipid in mitochondrial membrane.
2. It stimulates antibody formation i.e. antigenic
8. Lysophospholipids:
• Structure: Like lecithin and Cephalin, but contains only 1 fatty acid in position1
• Functions:
1. Lysolecithin is important in metabolism.
2. Lysocephalin is strong surface-active substance. It is used in manufacturing most
types of chocolates.
Hydrolysis of Glycerophosphatides
By Phospholipases: Hydrolyzes different phospholipids

DR. Mahmoud Ettaweel

 Sphingomyelin
• Structure:
1. Sphingosine.
2. Fatty acid attached to amino group at position 2.
3. Phosphate at position3.
4. Choline base (attached to phosphate).
• Functions:
- It is present in high concentrations in brain and nerve tissue
• Niemann Pick’s disease:
1. It is accumulation of large amounts of Sphingomyelin in liver due to deficiency of
sphingomyelinase enzyme.
2. It leads to mental retardation and death in early life.
GLYCOLIPIDS
- Formed of ceramide (Sphingosine + FA) attached to carbohydrates.
- Includes cerebrosides, Sulfolipids & Gangliosides.
1. Cerebrosides:
• Structure: • Formed of ceramide + Glucose (glucocerebroside).

Galactose (galactocerebroside).
• FA contain 24 carbons Cerebronic OR Nervonic
• Functions:
1- Cerebrosides are present in many tissues especially in the brain and myelin
of nerve fibers.
2- They act as insulators of nerve impulse.
• Gaucher’s disease:
-Def: Accumulation of cerebrosides (sphingolipids) in phagocytes due to
deficiency of “β glucocerebrosidase” enzyme.
-Manifestations: mental retardation, hepatomegally and bone disorder.
2. Gangliosides:
• Structure: Formed of ceramide + complex carbohydrate e.g. (NANA)
• Function:
1. They act as receptors at cell membrane.
• Degradation by: hexoaminidase enzyme.
• Tay Sachs disease:
- Def: Accumulation of gangliosides in brain and intestine due to deficiency
of hexoaminidase enzyme
-Manifestations: mental retardation, hepatomegally and blindness.
3. Sulfolipids (sulfatides):
• Formed of ceramide + galactose 3 sulfate.
❖ Importance of glycolipids : Found in
• Cell membranes • Myelin sheath • Receptors for hormones.
Q1- Enumerate sphingolipids:
• Sphingomyelin
• Glycolipids: (cerebrosides, Sulfolipids, Gangliosides)
Q2: Enumerate Choline containing lipids:
• Lecithin
• Plasmalogens
• Sphingomyelin

DR. Mahmoud Ettaweel

 Lipoproteins
❖ These are complex lipids formed of lipids conjugated with protein.
❖ They are present in c.m, mitochondria and plasma (plasma lipoproteins).
❖ Plasma lipoproteins convert water insoluble lipids into water soluble complexes. This
facilitates transport of lipids between blood and different tissues.
❖ The plasma lipids are triacylglycerols, phospholipids, cholesterol
(free and esterified) and free fatty acids.
❖ Methods used for separation of plasma lipids:
These methods include: electrophoresis, Ultracentrifugation,
gas liquid chromatography and thin layer chromatography
❖ The protein fractions are called Apo lipoproteins. They include :
FRACTION SOURCE MAIN LIPID ptn Amount Types

chylomicrons Intestine TG 2% A, B48,C & E.

VLDL Liver TG 12% B100, C & E

LDL Blood from Cholesterol, 22% B100

chylomicrons esters and
and VLDL phospholipids
HDL Liver Cholesterol, 50% A, C, D & E.
esters and
phospholipids
FFA.Albumin Adipose tissue FFA 99% Albumin

DR. Mahmoud Ettaweel

 MCQ
9. All the following statements are true with regard to phospholipid EXCEPT:
a- They can exist as zwitter ions b- They have surfactant properties
c- They are components of biomembranes d- They are resistant to the action of enzymes
10. Which of the following is NOT a phospholipid?
a- Sphingomyelin. b- Cerebrosides. c- Cephalin. d- Lecithin.
11. Sphingomyelin on hydrolysis yields all the following, EXCEPT:
a- Sphingosine b- Glucose c- Phosphate d- Choline
12. Cardiolipin:
a- Contains choline b- Is diphosphatidyl glycerol
c- Is a part of sphingolipin d- Is found in endoplasmic reticulum
13. A ganglioside on hydrolysis gives all the following, EXCEPT:
a- Fatty acid b- Glycerol
c- Sphingosine d- N-acetyl neuraminic acid
14. Phospholipids containing choline include all of the following
EXCEPT:
a- Phosphatidyl choline.
b- Sphingomyelin
c- Lecithin
d- Cardiolipins.
15. Ceramide consists of:
a- Sphingosine and galactose.
b- Sphingosine and FA.
c- Glycerol and galactose.
d- None of the above.
16. All of the following are glycolipids, EXCEPT:
a- Sulfatides.
b-Lecithin.
c- Ganglioside.
d- Cerebrosides.
17. All are sphingolipids, EXCEPT:
a- Sphingomyelin.
b- Sulfatides
c- Cephalin.
18. The sphingolipid "which contains NANA sialic acid is:
a- Sulfulipids.
b-Gangliosides.
c- Cerebrosides.
d-Sphingomyelin.
19. Which of the following is NOT phospholipid?
a- Cerebrosides
b- Cardiolipin
c- Lecithin
d. Sphingomyelin
20. Sphingosine is the backbone of all the following EXCEPT:
a- Lecithin
b- Ganglioside
c- Cerebrosides
d- Sphingomyelin

DR. Mahmoud Ettaweel

 Derived Lipids
❖ Def:
Produced by hydrolysis of simple or conjugated lipids or associated with lipids in nature.
❖ Includes:
1. FA 2. Steroids 3. Carotenoids
4. Ketone bodies 5. Fat soluble vitamins (Vit. K, E, D & A)

Steroids
- Compounds containing steroid nucleus (cyclopentano-perhydro-phenanthrene “CPPP”)

❖ Types of steroids and sterols are:

1. Cholesterol (animal origin).
2. Ergosterol (plant origin).
3. Vitamin D group (D2 and D3).
4. Bile salts.
5. Steroid hormones:
a) Male sex hormones.
b) Female sex hormones.
C) Adrenocortical hormones.
6. Digitalis glycosides.
Cholesterol
❖ Structure:
a. cyclopentano-perhydro-phenanthrene ring
b. -OH group at C3 (so it is an alcohol).
c. 2 methyl groups at C10 & C13 (- CH3 = I).
d. Long side chain at C17.
❖ Body cholesterol:
a. It is present in everybody cell (cell membrane) especially in:
- Adrenal cortex.
- Liver and kidney.
- Brain and nerve tissue.
b. Blood cholesterol:
- It occurs in the blood in 2 forms: free form and esterified form (combined to
fatty acids to form ester)
- The level of blood cholesterol is normally less than 220 mg/dl. Any
increase above this level is called: hypercholesterolemia

DR. Mahmoud Ettaweel

 ❖ Properties:
1. It is an alcohol, insoluble in water, soluble in fat solvents.
2. It forms characteristic crystals with broken corner.
3. It gives positive Lieberman’s test which runs as follows
cholesterol + Acetic acid + conc. sulphuric acid → Bluish green color.
❖ Functions of cholesterol: it is important for:
1. It enters in the structure of everybody cell particularly:
a) Cell membranes.
b) In nervous tissue.
2. Synthesis of steroid hormones.
3. Synthesis of bile salts.
4. Synthesis of vitamin D3.
Ergosterol
❖ Structure: Similar to cholesterol but differs in:
a) Extra double bond between C7 & C8.
b) The side chain is unsaturated and has extra methyl group.
❖ Properties: It is a plant sterol, poorly absorbed from small
❖ Functions: It gives vitamin D2 by ultraviolet rays.
Vitamin D group
❖ Structure:
1. Vitamin D3 is derived from 7-dehydrocholesterol by the rupture of second ring
by ultraviolet rays.

2. Vitamin D2 is derived from ergosterol by the rupture of second ring by

ultraviolet rays.

Bile acids and salts

Bile acids are hydroxyl derivatives of C24 steroid termed cholanic acid
❖ Types of bile acids: Primary & Secondary bile acids
A. Primary bile acids
• Cholic acid (3, 7, 12 trihydroxy cholanic acid)
• Chenodexy cholic acid (3, 7 dihydroxycholanic acid)

B. Secondary bile acids

- 2ry bile acids are formed from 1ry bile acids by the action of intestinal bacteria
(contain 7α dehydroxylase).
2ry bile acids are:

DR. Mahmoud Ettaweel

 • Deoxycholic acid (3, 12 dihydroxy cholanic acid).
• Lithocholic acid (3 monohydroxy cholanic acid).
C. Bile Salts
- Formed by & conjugation of bile acids with glycine or tourine then Na + or K+ to
form: • Na glycocholate • Na taurocholate
- Bile salts are excreted from liver & stored in gall bladder
- Bile salts pass to intestine during digestion of fat
- They are reabsorbed from intestine & back to liver (Enterohepatic circulation)
❖ Importance of bile salts: MDAPS
1. Main way for excretion of cholesterol.
2. Digestion of fat due to emulsification.
3. Absorption of fat due to formation of micelle.
4. Prevents precipitation of cholesterol & formation of cholesterol stones.
S. Stimulates liver cells to secrete more bile (Choleretic effect).

Carotenoids (terpenes)
❖ Definition:
a) Carotenoids are among the most common and most important natural Pigments.
b) They have yellow to red color.
❖ Types and structure:
a) Many types are present e.g. α, β and γ carotene.
b) All are hydrocarbons formed only of carbons and hydrogen.
c) Generally each carotene is formed of two ionone rings. Each ionone ring is connected
to two isoprene units, both are interconnected by methane group (-CH=CH-).
❖ Sources:
a) Plant sources: They are responsible for many colors of fruits and vegetables e.g.
carrots, orange, apricot, apple and tomato.
b) Animal sources: fats, butter, milk and egg yolk.
❖ Functions:
* Antioxidant * Antimalignant * Provitamin A

DR. Mahmoud Ettaweel

 Amino Acids
• Structure:
A. There are about 300 amino acids occurring in nature. Only 20 of them occur in
proteins.
B. Each amino acid has the following 4 groups or
atoms: attached to alpha (α) carbon:
1- Amino group: (NH2).
2- Carboxyl group: (COOH).
3- Hydrogen atom (H).
4- Side chain or radical group (R).
C. Characters of amino acids: all are
1. α-Amino acids: i.e. the amino group attached
to the second carbon (next to the carboxyl
group).
2. L-Amino acid i.e. α-amino group is
on the left side configuration.

• Classification of amino acids:

DR. Mahmoud Ettaweel 01004486188 37

➢ Chemical classification:
1. According to the fatty acids the amino acids are derived from:
Fatty acids Amino acids
1- acetic acid: 2c (CH3-COOH):
- Glycine: (alpha amino acetic acid).
2- Propionic: 3c (CH3-CH2-COOH):
- Alanine: (alpha amino Propionic acid)
- Serine: (alpha amino beta hydroxy
Propionic acid)
- cysteine: (alpha amino beta thiol,
Propionic acid)
- Phenylalanine: (alpha amino, beta
Phenyl Propionic acid)
- Tyrosine: (alpha amino, beta
parahydroxy phenyl Propionic acid)
- Tryptophan: (alpha amino beta indole
Propionic acid)
- Histidine: (alpha amino beta imidazol
Propionic acid)

3- butyric acid: 4c (CH3-CH2-CH2-COOH)

- Threonine:(alpha amino, beta hydroxy
butyric acid)
- Methionine:(alpha amino, gamma methyl
thiol butyric acid)

4- Valeric acid:5c (CH3-CH2-CH2-CH2-COOH)

- lsoleucine: (alpha amino, beta methyl
Valeric acid)
- Arginine: (alpha amino, delta guanido
Valeric acid)

5- Isovaleric acid: 5c
- VaIine: (alpha amino, Isovaleric acid)
6- Caproic acid: 6c
- Lysine: (alpha amino, epsilon amino caproic
acid)
7- Isocaproic acid: 6c
- Leucine: (alpha amino isocaproic acid)

8- Succinic acid: 4c dicarboxylic acid

- Aspartate: (alpha amino succinic acid)
- Asparagine:(alpha amino succinic

DR. Mahmoud Ettaweel 01004486188 38

9- Glutaric acid: 5c dicarboxylic acid
- Glutamate: (alpha amino glutaric acid)
- Glutamine: (alpha amino glutaric acid
amide)
10- pyrrolidine ring: 4c
- Proline:

2. According to if the amino acid is acidic, basic or neutral amino acids:

a) Acidic amino acids: contain more than one -COOH group. e.g.
Aspartate and glutamate.
b) Basic amino acids: contain more than one -NH2 group. e.g.
ornithine, lysine, Arginine and histidine.
c) Neutral amino acids: these are amino acids, which contain one COOH and
one -NH2 groups. e.g. glycine, alanine, etc.
3. According to the polarity of the radical (R):

4. Classification according to if amino acid is: aromatic, heterocyclic or aliphatic.

1. Aromatic amino acids: which contain phenyl or phenol ring:
a) Phenylalanine (phenyl ring).
b) Tyrosine (phenol ring).
2. Heterocyclic amino acids: which contain other type of rings:
a) Tryptophan (indole ring).
b) Histidine (imidazol ring).
c) Proline (pyrrolidine ring).
d) Hydroxyproline (hydroxy pyrrolidine ring).
3. Aliphatic amino acids: include other amino acids which contain no ring.
5. According to if the amino acid is: branched or non branched:
1. Branched amino acids: alanine, Leucine and lsoleucine.
2. Non-branched amino acids: Rest of amino acids.

DR. Mahmoud Ettaweel 01004486188 39

 6. Imino and amino acids:
1. Imino acids: Proline and, hydroxyproline.
2. Amino acids: Rest of amino acids.
7. Sulfur and hydroxyl containing amino acids:
1. Sulfer containing amino acids: cysteine, cystine and methionine.
2. Hydroxyl containing amino acids: serine, threonine.
➢ Nutritional classification of amino acids:

➢ Metabolic classification:

DR. Mahmoud Ettaweel 01004486188 40

• Amino acids that do not enter in protein structure:
A. Non alpha amino acids:
1. β-Alanine: It enters in the structure of a vitamin called pantothenic acid
2. Gamma amino butyric acid (GABA): This is a neurotransmitter formed from
glutamate in brain tissue.
3. Taurine: This occurs in bile combined with bile acids.

B. Amino acids which participate in urea cycle:

1. Arginine: (α-amino δ-guanido Valeric acid).
2. Ornithine: (α, δ- diamino Valeric acid).
3. Citrulline: (α-amino δ- urido Valeric acid).

C. Amino acids in intermediary metabolism: -

1. Homoserine: (γ-Hydroxy α-amino butyric acid)
2. Homocysteine: (γ-Thiol α-amino butyric acid)
D. Amino acids containing iodine: These are precursors of thyroid hormones:
1. Monoiodotyrosine. 2. Diiodotyrosine.
3. Triiodotyrosine (T3). 4. Tetraiodotyrosine (T4)
E. It is 2 molecules of cysteine (dicysteine) united together by removal of hydrogen
of -SH groups, It is important for protein structure.

• Function (biomedical importance) of amino acids

A. Structural function: enter in the structure of:
a) Body peptides and proteins: e.g. plasma proteins, tissue proteins, enzymes, etc.
b) Hormone: some hormones are amino acid derivatives e.g. thyroxin.
c) Amines: Some amino acid gives corresponding amines by decarboxylation e.g.
histidine gives histamine which is vasodilator.
B. Neurotransmitters: Some amino acids as glycine and glutamate act as N.T
C. Detoxication: Some amino acids are used in detoxication reactions

DR. Mahmoud Ettaweel 01004486188 41

• Properties of amino acids:
Physical Chemical
A. Solubility: Amino acids may be soluble in A. Properties of carboxyl (-COOH) and
water, dilute acids amino (-NH2) groups:
B. Optical activity: All amino acids - except B. Reaction with ninhydrin:
glycine are optically active because they 1. Ninhydrin is a substance that reacts with
contain asymmetric carbon atom. amino acids to give CO2, ammonia and
C. Meltin g point: Amino acids are present in aldehyde.
crystals with high ionic forces, stabilizing a) Ninhydrin reacts with liberated
these crystals. So amino acids have high ammonia to give blue colour.
melting points above 200°C i.e. they are very b) The intensity of the blue colour
stable molecules. indicates the quantity of amino acids
D. Amphoteric properties and isoelectric present. IT can detect 1 ug of a.a
point of amino acids = have both basic 2. Ninhydrin reaction is given also by
(-NH2) and acidic (-COOH) groups. ammonia, peptides and proteins.
- Monoamino-monocarboxylic acids present 3. Ninhydrin can react with proline and
in aqueous solutions as zwitter ion: It is the hydroxyproline (Imino) but it gives yellow
amino acid that carries both positive and
negative charges. It is electrically neutral and C. Reaction with fluorescamine:
cannot migrate in electric field. 1. Like ninhydrin, fluorescamine forms a
- Isoelectric pH (isoelectric point: Pi): it is blue complex with amino acids.
the pH at which the zwitter ion is formed. 2. It is more sensitive than ninhydrin, and
1) Each amino acid has certain pH at can detect nanogram quantities of a.a
Which zwitter ion is formed.
2) This pH is at midway between the pK D. Color reactions of amino: acids These
values of the carboxyl and amino groups. depend on the nature of radical (R).
3) Example: alanine 1-Millon’s reaction: for tyrosine→ Red.
i-In strongly acidic pH (at pH zero) alanine is 2. Rosenheim’s R: for tryptophan → Purple.
present mainly in the form of positively 3. Xanthoproteic R: for phenylalanine and
charged molecule. Its pK (PK1) = 2.34 tyrosine → Orange color.
ii- By adding NaOH, the carboxyl group loses
its proton (H+) and alanine carries both E. Peptide bond formation.
positive and negative charges (zwitter ion).
iii-By adding more NaOH, the solution F. Absorption spectrum of amino acids:
becomes strongly alkaline, and (-NH3) group 1. Amino acids are colorless. They do not
will lose its proton and alanine will become absorb visible light.
negatively charged. Its pK (PK2) = 9.69. 2. Aromatic amino acids (particularly
tryptophan) absorb ultraviolet light (wave
length 250-290 nm).

DR. Mahmoud Ettaweel 01004486188 42

 MCQ
1. One of the amino acids listed below is not basic:
a- Arginine b- Histidine c- Glutamine d- Lysine
2. Which of the following amino acid has a hydroxyl group?
a- Valine b- Threonine c- Leucine d- Histidine
3. All the following amino acids are neutral, EXCEPT:
a- Aspartic acid b- Tyrosine c- Glycine d- Threonine
4. All the following are branched chain amino acids, EXCEPT:
a- Valine b- Leucine c- Isoleucine d- Threonine
5. All the following are Sulphur containing amino acids, EXCEPT:
a- Cysteine b- Methionine c- Homocysteine d- Threonine
6. Guanido group is present in:
a- Arginine b- Tryptophan c- Histidine d- Proline
7. Indole ring is present in:
a- Arginine b- Tryptophan c- Histidine d- Proline

DR. Mahmoud Ettaweel 01004486188 43

 Peptides
• Definition: Peptides are compounds, formed of less than 50 amino acids linked
together by peptide bonds.
1. Dipeptide (2 amino acids and 1 peptide bond). 3. Oligopeptide (3-10 amino acids).
2. Tripeptide (3 amino acids and 2 p.b). 4. Polypeptide (10-50 amino acids).
• Peptide bond:
- Definition: It is a covalent bond formed between the carboxyl group of one amino
acid and the amino group of another.
- Mechanism: - it is formed by removal of water.
- Peptide formation needs energy getting from hydrolysis of ATP
- Characters: - Peptide bond is semi-rigid bond i.e. no free rotation can occur
around bond axis.
• Primary structure of peptides:
- It’s the arrangement of amino acids in a polypeptide chain.
- In a polypeptide chain the N-terminal amino acid (i.e. the only amino acid that contains
free amino group) is always to the left side.
- The C-terminal amino acid (i.e. the only amino acid that contains free carboxyl group)
is aIways to the right.

• Separation of peptides
A. By electrophoresis B. By exchange chromatography technique.
• BioIogicaIIy active peptide Peptides include many active compounds as:
A. Glutathione:
- Definition: it is a Tripeptide formed of three amino acids: glutamate cysteine
and glycine. It is also called “glutamyl-cysteinyl-glycine”.
Glutathione is commonly abbreviated as G-SH where -SH indicates the sulfhydryl
group of cysteine and it is the most active part of the molecule.
- Functions of glutathione:
1- Defense mechanism against certain toxic compounds (Detoxification).
2-Absorption of amino acid: glutathione has a role in transport of amino acids
across intestinal cell membrane..
3- Protect against cell damage and hemolysis of RBCs: Glutathione breakdown
the hydrogen peroxide (H2O2) which causes cell damage and hemolysis.
4- Activation of some enzymes.
5- Inactivation of insulin hormone.

DR. Mahmoud Ettaweel 01004486188 44

B. Hormones
1. Insulin and glucagon from Pancreas.
2. Vasopressin and oxytocin from posterior pituitary gland.
3. ACTH from anterior pituitary gland.
C. β-Lipotropin:
- Is polypeptide produced by anterior pituitary.
- Is the precursor of β-endorphin.
- β-endorphin acts as neurotransmitter and neuromodulator.
- It has analgesic effect powerful 18-30 times than morphine.
D. Bradykinin:
1. It is released from specific plasma proteins by specific proteolytic enzyme.
2. It acts as a potent smooth muscle relaxant and produces vasodilatation and
hypotension.
E. Antibiotics: e.g. valinomycin.
F. Antitumor agent: e.g. bleomycin.
G. Aspartame:
- It is a dipeptide (aspartic acid and phenylalanine) that serves as sweetening
agent. It is used in replacement of cane sugar.
H. Atrial natriuretic peptide:
1. It is a peptide produced by specialized cells in the heart and nervous tissue.
2. It stimulates the production of dilute urine (opposite to vasopressin).

DR. Mahmoud Ettaweel 01004486188 45

 MCQ
8. The following amino acids have hydrophobic side chains, EXCEPT.
a- Tyrosine b- Alanine c- Leucine d- Valine
9. Imidazole ring is present in:
a- Arginine b- Tryptophan c- Histidine d- Proline
10. Which of the following amino acids has a non-polar side chain?
a- Serine b-Valine c- Asparagine d- Threonine
11. All the following are glucogenic amino acids, EXCEPT:
a- Glycine b- Serine c- Leucine d- Aspartic acid
12. Which of the following amino acids has a net physiological pH?
a- Glutamic acid b- Lysine c- Valine d- Leucine
13. Which is the ketogenic amino acid?
a- Alanine. b- Glutamic acid c- Leucine d- Aspartic acid
14. All the following are essential amino acids, EXCEPT:
a- tyrosine b- Lysine c- Valine d- Phenylalanine.
15. Non-essential amino acids:
a- Are not seen in tissue proteins b- Could be synthesized in the Body
c- Have no role in body metabolism d- Have aromatic ring structure
16. At isoelectric pH, the amino acids, and proteins show;
a- Maximum net charge b- Maximum mobility in electric field
c- Maximum precipitability d- Maximum buffering action
17. Enzymes are activated by phosphorylation of which amino acid residue:
a- Cysteine b- Serine c- Glutamic acid d- Lysine.
18. The following are aliphatic amino acids,
a- Alanine, valine, and glycine. b-Glycine, leucine, and serine.
c- Threonine, serine, and glutamic acid. d. Phenylalanine, tryptophan, and histidine.
19. All the following are heterocyclic amino acids, EXCEPT:
a- Histidine. b- Phenylalanine. c- Tryptophan d- Proline.
20. The following are basic amino acids:
a- Tryptophan and phenylalanine. b-Alanine and glycine.
c- Histidine, lysine, arginine. d- Valine, leucine, and isoleucine.
21. Non-polar amino acids include:
a- Glutamine and asparagine. b- Phenylalanine and tryptophan.
c- Cysteine, serine, and tyrosine. d- Lysine, arginine and histidine.
22. An essential hydroxy-containing amino acid is:
a- Tyrosine. b-Serine. c- Threonine. d-Hydroxy lysine.
23. Semi-essential amino acids include:
a- Valine and threonine. b-Arginine and histidine.
c- Cysteine and methionine. d-Phenylalanine and tyrosine.

DR. Mahmoud Ettaweel 01004486188 46

 Proteins
• Nature of proteins:
A. Composition:
1. Proteins are macromolecules formed of amino acids united together by
peptide bonds.
2. Amino acids are commonly found in proteins in different proportions.
3. Some proteins are formed of 2 or more polypeptide chains.
B. Size of proteins.
1. Proteins having a very high molecular weight, ranging from 5,000 to several
millions.
2. The term protein is applied to describe molecules greater than 50 a.a.
3. Molecules contain less than 50 amino acids are termed peptides.
• Functions of proteins:
1. Enzymes: Enzymes are protein
2. Transport: Of small molecules and ions e.g.
a. Hemoglobin is a carrier for oxygen.
b. Lipids are transported as lipoproteins.
3. Structural elements: e.g.
a. Cell membrane contains proteins in the form of glycoproteins.
b. Skin and bone: e.g. contains proteins in the form of collagen.
4. Hormonal regulation:
a. Some hormones are protein in nature e.g. growth hormone.
b. Cellular receptors that recognize hormones are proteins
5. Defense mechanism:
a. Antibodies: (immunoglobulins) are protein in nature.
b. Keratin found in skin and other tissues is protein that protect against
mechanical and chemical injury.
6. Blood clotting: Coagulation factors are proteins.
7. Storage: as ferritin which is a storage form of iron.
8. Control of genetic expression: many regulators of genes are protein in nature.
• Conformation of proteins = (protein structure):
A. Primary structure:
- Definition: It is the arrangement of amino acids in the polypeptide chain.
- Bonds responsible for the primary structure: The peptide bonds “covalent”.
- Mechanism:
1. Each polypeptide chain starts on the left side by free amino group of the first
amino acid, It is termed N-terminal (or N-terminus) amino acid.
2. Each .polypeptide chain ends on the right side by free carboxyl group last amino
acid, It is termed C-Terminal (or C-terminus) amino acid.

DR. Mahmoud Ettaweel 01004486188 47

 3. The remaining amino acids in the chains are termed: amino acid residues
4. The types and arrangement of amino acid in each protein is determined by the
genetic information present in DNA.

B. Secondary structure:
- Definition: It is the spatial relationship of adjacent amino acid residues.
- Bonds responsible: Hydrogen bond. It is the bond between
the hydrogen of -NH group of one amino acid residues and the carbonyl oxygen (C=O)
of the fourth one
- Mechanism:
1. Secondary structure results from interaction of adjacent amino acid residues
(first and fourth).
3. There are 2 main forms of secondary structure α-helix and β-pleated sheets:
The α-helix β-pleated sheets
- Shape & formation: It is a rod like - Shape & formation:
structure with the peptide bonds a) This structure is formed between two or
coiled tightly inside and the side more separate polypeptide chains.
chains of the residues (R) extending It may also be formed between segments of
outward from the chain. the same polypeptide chain.
- Characteristics: b) Hydrogen bond is also responsible for its
1) Each (C=O) of one amino acid is formation. It occurs between (-NH) group of
hydrogen bonded to the (-NH) of the one chain (or segment) and (C=O) of group
next fourth amino acid in the chain of adjacent chain (or segment).
(1→4 ) - Two types of β-sheets are present:
2) The complete turn distance equals 54 1) Parallel β-sheets:
nm. in which the two polypeptide chains run in
3) Each turn contains 3.6 amino acids the same direction.
residues. 2) Antiparallel β-sheets:
in which the two polypeptide chains run in
opposite direction.

DR. Mahmoud Ettaweel 01004486188 48

C. Tertiary structure:
- Definition: This is the final arrangement of a single polypeptide chain resulting from
spatial relationship of more distant amino acid residues.
- There are two forms of tertiary structures:
a) Fibrous: which is an extended form e.g. keratin, collagen and elastin.
b) Globular: which is a compact form and results from folding of polypeptide chain
e.g. myoglobin.
- Bonds responsible for tertiary structure are:
a) Hydrogen bonds: within the chain or between chains
b) Hydrophobic bonds: between the nonpolar side chains (R) of neutral amino acids.
c) Electrostatic bonds: (salt bonds): between oppositely charged groups in the side
chains of amino acids e.g. amino group of lysine and carboxyl group of Aspartate.
d) Disulfide bonds: between residues within the chain.

DR. Mahmoud Ettaweel 01004486188 49

D. Quaternary structure
- Many proteins are composed of several polypeptide chains. Each poly peptide chain is
called: subunits. Each subunit has its own primary, secondary and tertiary structure,
- Bonds responsible for quaternary structure:
a) Hydrogen bond.
b) Hydrophobic bond.
c) Electrostatic bond
- Examples of proteins having quaternary structure:
a) Insulin: 2 subunits.
b) Lactate dehydrogenase enzyme: 4 subunits.
c) Globin of hemoglobin: 4 subunits.

• Denaturation
A. Definition: unfolding and loss of secondary tertiary and quaternary structure.
- Does not affect primary structure i.e. not accompanied by hydrolysis of peptide bond.
- Denaturation may be reversible (in rare cases)
B. Effect of protein denaturation:
1. Loss of biological activity: e.g. insulin loses its activity after denaturation.
2. Denaturated protein are often insoluble.
3. Denaturated protein are easily precipitated.
C. Denaturating factors include:
1. Heat: causes coagulation and precipitation of certain proteins like albumin.
2. Organic solvents: They interfere with hydrophobic bonds of proteins.
3. Detergents: They contain both hydrophobic and hydrophilic groups i.e. amphipathic.
They interfere with hydrophobic bonds of proteins.

DR. Mahmoud Ettaweel 01004486188 50

 4. Strong acids or bases: They lead to change in pH which affects the charges on
polypeptide chains. As a result, hydrogen and electrostatic bonds will be disrupted.
5. Heavy metals: as lead and mercury salts:
a) They form ionic bonds with negatively charged ions in polypeptide chains. This
leads to disruption of electrostatic bonds.
b) They unite with -SH (sulfhydryl) groups of proteins causing its denaturation (-S-Hg).
6. Enzymes: e.g. Digestive enzymes.
7. Urea, ammonium sulphate and sodium chloride: cause precipitation of proteins.
8. Repeated freezing and thawing: cause disruption of hydrogen and other bonds.
• Classification of proteins

➢ Simple proteins,
A. Albumin and globulins:
Albumin globulins
coagulated by heat coagulable Same
biological value high Same
Solubility Soluble in water Soluble in salt solution
Molecular weight 68.000 150,000
By full saturated By half saturated
Precipitation
ammonium sulphate ammonium sulphate
Sources:
1)Blood Serum albumin Serum globulins
2)Milk Lactalbumin Lactglobulin
3)Egg Egg albumin Egg globulin

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 B. basic proteins: Globins (=histones) and protamines:
Both are basic proteins i.e. rich in basic amino acids.
Globins (=histones) Protamins
Type of basic amino acid Histidine Lysine and Arginine
1. In salt solution
Solubility In salt solution
2. In 70% ethanol
Sources:
1. Combined with DNA 1. In plants & animals In fish
2. Combined with Heme 2. To form hemoglobin
C. Gliadins and Glutelins:
1. Both are acidic proteins i.e. rich in acidic amino acids: glutamic acid.
2. Both are present in cereals
3. Both are soluble in diluted acids and alkalies. Gliadins also soluble in 70%
ethanol.
D. Scleroproteins:
They include: keratin, collagen, elastin and reticulin.
1. Keratins:
a) Location: They are found in hair, nail, enamel of teeth, and outer layer of skin.
b) Structure: They are α-helical polypeptide chains. They are rich in cysteine
(which provides disulfide bonds between adjacent polypeptide chains).
c) Solubility: It is insoluble due to their high content of hydrophobic a.a
2. Collagen
a) Types of collagens:
- There are more than 12 types of collagen. Type I is the most common in human
body (90%) of cell collagens.
- Collagens form about 30% of total body proteins.
b) Functions and Location:
- It is the protein of connective tissue present in skin, bones, tendons and blood
vessels.
- Bones and teeth are made by adding mineral crystals to the collagen.
- Collagen may be present as a gel e.g. in extracellular matrix or in vitreous
humour of the eye.
c) Structure:
1) Collagen molecules are simple protein; consist of 3 polypeptide chains called
α-chains. They are twisted around each other forming triple helix molecule.

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 i- The 3 polypeptide chains are held together by hydrogen bonds
ii- each chains about 300 nm length and 1 .5nm in diameter.
iii- Each chain is formed of 1050 amino acids.
2) Amino acids composition acid sequence:
i- Amino acids composition: Collagen contains 33% glycine (the smallest amino acid), 10%
proline, 10% hydroxy proline and 1% hydroxylysine.
ii- Amino acids sequence: Every third amino acid in the α-chain is glycine. The repeating
sequence is glycine-X-Y, where X is frequently proline and Y is often hydroxy-proline or
hydroxylysine.
4) Glycosylation: Collagens are present in the form of glycoprotein. Glucose and galactose are
commonly attached to collagen
5) Collagen molecule has very firm structure due to:
i- Each helical turn contains only 3 amino acids. For other proteins, each turn contains 3.6
amino acids.
ii- Glycine (the smallest amino acid) forms 33% of total molecule. This makes the
polypeptide chains compact.
iii- The high content of hydroxyproline and hydroxylysine increase the number of hydrogen
bonds.
d) Collagen synthesis:
1. Collagens are formed by connective tissue cells called fibroblasts.
2. Intracellular location: The polypeptide chains of preprocollagen are synthesized on the
rough endoplasmic reticulum, where preprocollagen is cleaved → Procollagen + Signal (pre)
sequence.
3. Proline and lysine residues are hydroxylated by a reaction that requires O2 and
vitamin C
4. Glycosylation by glucose and galactose that added to hydroxylysine residues.
5. The Procollagen (in the form of triple helix) is secreted from the cell and cleaved → Collagen
5. Cross links are produced.
e) Solubility and denaturation:
1) Solubility: Collagen is insoluble in all solvents. It is protein of low biological value and not
digestible.
2) Denaturation:
- When collagen is heated, it loses all of its structure. The triple helix unwinds and the chains
are separated. Then when this Denaturated mass cools down, it soaks up all of the
surrounding water like sponge, forming Gelatin.
- Gelatin is soluble in water and digestible.
- Gelatin is given for patients during convalescence (in the form of jelly).
f) Collagen diseases: (Scurvy):
i- It is due to a deficiency in ascorbic acid (vitamin C). See vitamins.

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 3. Elastin:
a) Characters:
- It is connective tissue protein. It is rubber like i.e. it can be stretched to several times
as their normal length, but recoil to their original shape when the stretching force is
relaxed
b) Location:
It is present in lungs, the walls of large blood vessels and elastic ligaments.
C) Structure:
1) Elastin is formed of 4 polypeptide chain.
2) Elastin is similar to collagen, being rich in glycine (1/3 of its a.a) and proline. It is poor
in hydroxyproline hydroxylysine.
3) The 4 polypeptide chains are interconnected through their lysine residues. The 4
lysine residues are linked together form a cyclic structure termed: desmosine.
Elastin is capable of undergoing 2 way stretch, due to its content of desmosine.
Role of α1-antitrypsin (α1-AT) in : elastin degradation:
1) α1-antitrypsin is an enzyme produced mainly by liver. It is also produced by blood
cells monocytes and macrophages.
2) It is present in blood and other body fluids.
3) It inhibits a number of enzymes and destroys proteins.
4) Role of α1-AT in the lungs: In the normal lung, the alveoli are exposed to low levels of
elastase enzyme released from neutrophils. Their proteolytic activity can destroy the
elastin in alveolar walls: This elastase enzyme activity is inhibited by α1-antitrypsin.
5) Deficiency of α1-AT: Leads to destruction of connective tissue of alveolar walls by
neutrophils elastase. This leads to lung disease called: emphysema.

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 collagen Elastin
Number of chains 3 4
Amino acids 1/3 glycine, 1/3 glycine, rich in proline,
rich in proline, less hydroxyproline and
more hydroxyproline, free from hydroxylysine
*Fibrous in extended form
Structure Fibrous
*Globular in relaxed form
2 Directions due to
Direction of stretch One direction
presence of desmosine

➢ Conjugated proteins: On hydrolysis, they give protein (prosthetic group).They

include: part (apoprotein) and nonprotein part
A. Phosphoprotein:
1. These are proteins conjugated with phosphate group.
2. Phosphate is attached to -OH group of serine (phospho-serine) or threonine
(phospho-threonine) present in protein part.
3. Examples:
a) Casein: A milk proteins b) VitelIin: Present in egg yolk.
c) Phosphoenzyme: Phosphorylation (addition of phosphate to an enzyme) may
activate or inactivate enzyme according to its type.
B. lipoproteins
C. Glycoproteins and proteogIycans
D. Nucleoproteins
E. Chromoproteins:
1. They are proteins conjugated with colored elements.
Metalochromoproteins Non-metalochromoproteins
(contain colored metal) (contain colored pigment)
1- All iron containing proteins 1- Flavoprotein (yellow) contain Flavin
(red) pigment e.g. FAD.
2-All copper containing proteins 2- Carotenoids: they give vitamin A.
(greenish blue). 3- Melanoproteins: (brown to black)
e.g. melanin pigments of hair and iris.
F. Metaloproteins: These are proteins conjugated with metals

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G. Hemoproteins
- Definition: Hemoproteins are conjugated protein formed of protein part (globin)
and nonprotein prosthetic part (Heme).
1. Hems containing iron (red in color). Thus hemoproteins are considered
Metaloproteins.
2. Hemoproteins include many biologically active compounds as:
a) Hemoglobin: This carries oxygen.
b) Myoglobin: This stores oxygen in muscles.
c) Respiratory enzymes: These use oxygen.
- Structure of Heme:
1. Four Payrol rings are united together to form protoporphyrin III.
2. Iron in ferrous state (Fe++) is incorporated in protoporphyrin III to form heme.

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▪ Hemoglobin:
1. It is a Metaloproteins formed of heme and globin.
- Globin is a globular protein rich in histidine amino acids. It forms about of 95% of
haemoglobin molecule.
- Globin is a protein having a quaternary structure. It is formed of
2 α chain (each 141 amino acids) and 2 β chains (each 146 amino acids).
Functions of hemoglobin:
1. Carries O2 to tissues and removes CO2 from them to the lungs.
2. Acts as blood buffer. 3. Synthesis of heme. 4. Structure of hemoglobin.
5. Properties of hemoglobin. 6. Hemoglobin derivatives.
▪ Myoglobin
1. It is found only in the cytosol of red skeletal muscle and cardiac muscle. It gives
these tissues their characteristic red color.
2. It is formed of one heme molecule attached to one polypeptide Globin.
3. Myoglobin has much higher affinity for oxygen than hemoglobin. It is unable to
release it except under very low oxygen tension.
4. Myoglobin concentration is increased in blood in myocardial infarction.
- Clinical aspects:
1. Myoglobinuria
a) It is the release of myoglobin from muscles after massive crush injury.
b) Myoglobin is excreted in urine, colors it dark. It may cause renal tubular
obstruction and renal failure.
2. Plasma myoglobin is increased following myocardial infarction, but
measurement of serum myocardial enzymes provides a more sensitive index of
myocardial infarction.
3. Sickle cell anemia:
a) The blood cells of these patients contain abnormal hemoglobin called
hemoglobin S (HbS).
b) A molecule of HbS contains 2 normal α-chains and 2 mutants - chains in which
glutamate at position six has been replaced by valine.
4. Thalassemias: Are anemias characterized by reduced synthesis of either alpha
chain (α-Thalassemias) or beta chain (β-Thalassemias) of hemoglobin.

DR. Mahmoud Ettaweel 01004486188 57

 ENZYMES
• Definition: These are specific protein catalysts that accelerate the rate of chemical reactions.
- Enzyme structure is not changed by entering the reactions.
- Enzyme does not affect the equilibrium constant (i.e. end products) of the reactions.
• Cellular distribution of enzymes:
A. Intracellular enzymes: Produced and act inside the cells e.g. metabolic enzymes.
B. Extracellular enzymes: Produced inside the cells and act outside the cells e.g. digestive
enzymes.
Properties of ENZYMES
- The general properties of enzymes are those of proteins:
1. They are globular proteins.
2. They can be denatured by physical and /or chemical agents and they loose their biological
function as the denaturation change their conformation.
3. Enzymes are usually specific in action and the specificity varies in degree (see later).
4. Some enzymes are simple proteins, others are conjugated proteins.
5. Each enzyme has a characteristic tertiary structure and undergoes a conformational change
suitable to the specific substrate
6. Some enzymes are secreted as proenzymes (zymogens) then they are activated at the time of
action.

ENZYME STRUCTURE

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 Zymogens
They are inactive enzymes.
1. Zymogens are inactive because their catalytic sites are masked by a polypeptide chain.
2. Activation of zymogen, into active enzyme is done by removal of the polypeptide chain to open
the catalytic site for its substrate.
3. Examples of zymogens: are pepsinogen and trypsinogen.

ENZYMES SPECIFICITY
1. Relative specificity: One enzyme acts on compounds having the same type of bonds
e.g. lipase enzymes act on different TAG
2. Group specificity: the enzyme acts on a special type of bond at specific site and attached
to specific groups e.g.:
- Pepsin: acts on peptide bonds between amino group of aromatic amino acid and
carboxylic group of another amino acid.
- Trypsin: acts on peptide bonds between carboxylic group of basic amino acid and amino
group of another amino acid.
3. Optical specificity:
- Enzymes act on D or L isomers e.g.
D - Amino acid oxidase acts only on D-amino acids
L- Amino acid oxidase acts only on L-amino acids
- Enzymes act on specific type of linkages according to the type of linkage (α or β) of
the compounds attached to it e.g.
α Amylase hydrolyses α-1-4 glycosidic linkage of starch.
4. Absolute specificity: One enzyme acts only on one substrate e.g. urease enzyme acts only
on urea.

DR. Mahmoud Ettaweel 01004486188 60

 MECHANISM OF ENZYME ACTION
A. Energy of activation:
- All the reactions that proceed from initial substrates (initial state) to products
(final state) consume energy. This is called free energy of the reaction.
- However the substrates do not become products directly, but must be energized
(absorb energy) to reach an activated or transition state. This
energy is called activation energy.
- At transition state, there is a high probability that a chemical bond will be made
or broken to form the product.
- The definition of activation energy: is the amount of energy required to raise 1
mole of substance to the transition state.
- The effect of enzymes: is to decrease the energy of activation.

B. Active site:
1) During the enzyme action, there is a temporary combination between the enzyme
and its substrate forming enzyme-substrate complex.
This occurs at active site of enzyme.
2) This is followed by dissociation of this complex into enzyme again and products.

C. Theories of enzyme action: Two theories have been proposed to explain the specificity of
enzyme action:
a) The lock and key theory: The active site of the enzyme is complementary in conformation to
the substrate so that enzyme and substrate “recognize” one another.
b) The induced fit theory: The enzyme changes shape upon binding the substrate, so that the
conformation of substrate and enzyme protein are only complementary after the binding
reaction.

DR. Mahmoud Ettaweel 01004486188 61

 CLASSIFICATION OF ENZYMES
Oxidases Oxidases forming water (H2O): e.g.
Catalyze the removal of H or cytochrome oxidase
e- from substrate but 2. Oxidases forming hydrogen peroxide
use only oxygen as a (H2O2).
hydrogen acceptor and form They are flavoproteins containing either FMN
water or H2O2 as a reaction or FAD
product.
Catalase: is present in all cells and tissues,
especially liver, kidney and erythrocytes.
In the catalase reaction, one molecule of
H2O2
Hpdroperoxidase act as a substrate and the other molecule act
Enzymes utilizing as hydrogen donor.
H2O2 as substrate. Peroxidase: present in RBCs, milk and
leucocytes.
1- Peroxidase uses H2O2 as substrate and an
Oxidoreductases organic substrate as hydrogen donor. e.g.
(redox enzymes) ascorbic acid, glutathione
Dehydrogenases a) Dehydrogenases depend on nicotinamide
These remove hydrogen from coenzymes (NAD, NADP)
one substrate to a hydrogen b) Dehydrogenases depend on riboflavin
carrier. They cannot use coenzymes (FAD and FMN).
oxygen as a hydrogen
acceptor.
Dioxygenases: Two atoms of oxygen
molecule are incorporated into the
Oxygenase substrate. As in tryptophan metabolism Mono-
oxygenase: Only one atom of molecular
They catalyze the direct oxygen is incorporated into the substrate in
incorporation of oxygen into the form of hydroxyl group (termed
the substrate. hydroxylases or mixed function oxidases), they
require a hydrogen donor

They catalyze transfer of an activated

Transglycosylases
glycosyl (sugar) residue. Usually activation by
2- (glycosyl transferases):
Transferases UDP glucose
These are enzymes They catalyze transfer of phosphoryl group
Transphosphorylases
which catalyze 1. kinases
(phosphotransferases):
transfer of 2. phosphoglucomutases
functional groups They catalyze transfer of acyl group
(G) other than Transacylases
(R-CO) and they need coenzyme A (COA) as a
hydrogen (acyl transferases)
carrier for acyl group
These transfer NH2 group from amino acid to

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 Transaminases α-ketoacid to produce a new amino acid,
vitamin B6 is a coenzyme
These transfer one carbon e.g. CH3
group from methyl donor to methyl acceptor.
The methyl donor is mainly S-adenosyl-
methionine.
Transmethylases
The methyl carrier is methyl tefrahydrofolic
(methyltransferases)
acid ; and methyl-cobalamine
Glycosidases. Amlyases α 1,4 glucosidase):
act on glycosidic linkage Starch maltose
causing its separation by
3- hydrolysis
Hydrolases Esterases Lipase: Triglyceride Glycerol + 3Fatty acids
These attack the ester linkage
These enzymes i.e. (linkage between acidic
act by splitting and alcoholic group)
(cleavage) of a Endo-peptidase: These act on intenal
certain bond bond in the polypeptide chain e.g.: pepsin.
Peptidases
by adding water. Exo-peptidase: They are divided into:
Split the peptide linkage
Carboxypeptidase: act on the carboxylic end
(CO-NH) of proteins.
Aminopeptidase: act at the amino end of
protein chain.
These catalyze the addition or Dehydratases (or hydratases): they
removal of groups e.g. catalyze removal or addition of water or
4. from the substrate.
H2O , NH3 or CO2,
Lyases:
without hydrolysis, oxidation Decarboxylases. They catalyze
or reduction. splitting of CO2.
They catalyse the Aldose-ketose isomerases
5.
interconversion
Isomerases
of two isomers.
These enzymes link two (1) Amide synthetase: ( C —N )
6.
molecules using energy from (2) Carboxylase:
ligases
ATP

DR. Mahmoud Ettaweel 01004486188 63

 COENZYMES
1- According to the structural basis into:
A- Vitamins Coenzymes:

Vitamin Coenzyme derivative Group carried in activated form

Thiamine (vitamin B1) Thiamine pyrophosphate(TPP) Aldehyde
Riboflavin (vitamin B2) Flavin adenine dinucleotide Hydrogen carrier
Flavin mononucleotide (FAD, FMN)
Nicotinate (niacin) Nicotinamide adenine dinucleotide, Hydrogen carrier
Nicotinamide adenine dinucleotide
Pyridoxine, pyridoxal Pyridoxal phosphate(PLP) Amino group
Pyridoxamine (vitamin B6)
Pantothenic acid CO enzyme A Acyl group
Biotin Carboxbiotin CO2
Folate Tetrahydrofolate(THFA) One carbon unit
Cobalamin (vitamin B12) Cobamide coenzymes - Methylcobalamine
- Deoxyadenosylcobalamine
Lipoic acid Lipoamide Acyl group, Hydrogen carrier
Quinone Ubiquinone Electrons
Vitamin C L- ascorbic acid Hydrogen carrier
B- Non Vitamins Coenzymes:
1- Nucleotide coenzymes (UDP-glucose, others nucleotide derivatives of carbohydrates): ATP.
2- Nucleoside: S adenosyl methionine (SAM) .
3- Peptide coenzymes (glutathione :GSH)

2- According to the functional basis into:

Coenzymes for transfer of H Coenzymes for group transfer
Hydrogen carriers Other than H
1. NAD+ and NADP+ 1. ATP, GTP, CTP etc.
3. Lipoic acid 2. Thiamin pyrophosphate (TPP).
5. Vitamin C 3. Coenzyme A (CoA)
2. FMN and FAD 5. Folic acid
4. Coenzyme Q 4. Pyridoxal phosphate (B6)
6. Glutathione. 6. Biotin

DR. Mahmoud Ettaweel 01004486188 64

 FACTORS AFFECTING ENZYME ACTIVITY
1. Concentration of enzyme: The initial velocity of a reaction is directly proportional to the
amount of the enzyme present, provided that all other conditions remain constant.
2. Concentration of substrate:
The initial velocity of a reaction is directly proportional to the amount of substrate present till it
reaches a maximum point known as maximum velocity (Vmax), where any further increase in
the amount of substrate causes no increase in the velocity of the reaction. This is true if all
other conditions especially enzyme concentration remain constant.

Zero order

1st order

a) Definition of maximum velocity (V max): It is the maximum point in substrate velocity curve
where any further increase in the amount of substrate causes no increase in the velocity of the
reaction due to enzyme saturation.
c) Michaelis constant Km
- Def: It is substrate concentration that produces half maximum velocity.

d) Important conclusions about Michael is-Menten kinetics:

- Km is a constant, characteristic of an enzyme and a particular substrate. Km reflects the affinity
of the enzyme for the substrate.
- The smaller the Km value → the more active the enzyme:
i- Small (low) Km reflects a high affinity of the enzyme for substrate i.e. low concentration of
substrate is needed to half saturate the enzyme.
ii- Large (high) Km reflects a low affinity to the enzyme for substrate i.e. high concentration
of substrate is needed to half saturate the enzyme.

DR. Mahmoud Ettaweel 01004486188 65

 3. Effect of temperature:
- The optimal temperature for enzymatic activity in human body is 37 °C i.e. the temperature of
the cells.
- At zero temperature, the enzyme is inactive. The reaction velocity increases with increase of
temperature until a maximum velocity is reached.
- Further elevation of the temperature results in a decrease in reaction velocity. At 55°C - 60°C,
most enzymes are denaturated and become permanently inactive.
4. Effect of pH:
- The optimal pH for enzyme activity is that pH at which the enzyme acts maximally.
- Above or below this pH, the ionic state of both enzyme and substrate will be changed, and the
rate of reaction will therefore decrease.
- Each enzyme has its own optimal pH e.g.
- Salivary amylase 6.8. - Pepsin 2
- Trypsin 8 - Alkaline phosphatase 8.4
- Extremes of pH can also lead to denaturation of the enzyme.

5. Effect of Co-enzymes concentration:

- Co-enzymes concentration has the same effect and gives the same curve of substrate
concentration on enzymatic activity, as NAD .
6. Effect of physical agents:
- Red and blue lights increase the enzyme activity.
- Heating, shaking stirring inhibit enzyme activity by denaturation.
- Ultra violet rays and infrared rays inhibit enzyme activity.
7. Effect of time;
- In all the previous factors, time must be taken into consideration, and its effect on enzyme
kinetics must be measured against time.
8. Effect of product concentration:
- Increased product concentration decreases enzyme activity, this may be due to:
1. Change in the pH of the medium.
2. The product is more or less similar to the substrate, so it may compete it to catalytic site of
the enzyme
3. The product may bind to the enzyme at the allosteric Site (in case of allosteric enzyme).

DR. Mahmoud Ettaweel 01004486188 66

 9. Enzyme activators:
- Activators increase the rate of enzyme catalyzed reactions.
- Velocity of the reaction depends on activator concentration.
- Some enzymes are activated by different ways:
A. Removal of peptide converts inactive forms of the enzyme (zymogen) to active.
Pepsin or HCI
e.g. pepsinogen pepsin.
B. Some enzymes containing SH groups e.g. glyceraldehyde 3-P dehydrogenase
require reducing agents (vitamin C) to be activated.
C. Some enzymes require minerals, they are called metal activated enzymes eg.
- Cl- for amylases (non metal ions) - Mg++ for kinases
D. Allosteric activators (Allosteric modifiers): The binding of allosteric activator produces
conformational changes in the protein structure of the enzyme resulting in increased velocity
of the reaction
e.g. AMP is an allosteric activator of phosphofructokinase enzyme.
10. Enzyme inhibitors:

MCQ
1. Which of the following is NOT true regarding enzymes?
a- Enzymes are proteins and can be denatured.
b- Enzymes act at a very low concentration.
c- Enzymes will only react with one or a very small number of compounds.
d-Enzymes are very small molecules, much smaller than their substrates.
2. All the following statements are true with regard to enzymes,
a- Enzymes lower activation energy. b- They alter equilibrium of the reaction
c- They accelerate the chemical reaction d- Most of the enzymes are proteins in nature
3. Enzymes which are synthesized in inactive form are called:
a- Co-enzymes b- Apo-enzymes c- Lysozymes d. Pro-enzymes (zymogen)
4. All of the following enzymes are oxidoreductases EXCEPT:
a. Glutathione peroxidase. b. Dioxygenase.
c. Catalase. d. Aldolase.
5. An example of Iyase is:
a- Glutamine synthetase b- Fumarase
c- Cholinesterase d- Amylase
6. The enzyme belonging to the ligase class is:
a- Glycogen synthase. b- Glutamine synthetase.
c- Porphobilinogen deaminase. d- Histidine decarboxylmse.
7. Coenzymes are:
a- Dialyzable, non-protein molecules. b- Colloidal protein molecules.
c- Structural analogues of enzymes. d- Different forms of the same enzyme.

DR. Mahmoud Ettaweel 01004486188 67

 Enzyme inhibitors
- Definition: These are substances that can diminish the velocity of enzymatic reactions.

Enzyme inhibitors
Reversible inhibitors
- Bind to enzymes through non covalent bonds. Irreversible inhibitors
- Dilution of the enzyme-inhibitor complex dissociates the reversibly bound
inhibitor and recovery of enz. activity.
A. Competitive inhibitors B. Non-competitive
- Similar to substrate. - Inhibitor and substrate -This type of inhibition
- compete with substrate for active site of the bind to different sites cannot be reversed by
enzyme. on the enzyme. adding more substrate
- Both substrate (S) and inhibitor (I) can bind with - The inhibitor does not - The inhibitor alters the
the catalytic site of the enzyme to form either alter the catalytic site. catalytic site.
Enz-S-complex or Enz-l-complex. - There is no structural - Irreversible inhibitors
- The combination between enzyme and similarity between include the following:
substrate or inhibitor depends on: substrate and inhibitor. 1. All compounds that
1) Concentration of substrate. - The inhibitor can bind produce Denaturation
2) Concentration of inhibitor. either free enzyme or of proteins.
3) Affinity of both inhibitor and substrate to the the enzyme-substrate 2. Inhibitors of
active site of the enzyme. complex. Both enzyme sulfhydryl group
- Example of competitive inhibitors: inhibitor complex and 3. Antienzymes: e.g.
1) Malonate and Succinate: both compete for the enzyme substrate Antithrombin III
catalytic site of Succinate DH. inhibitor complex are 4. Removal of catalytic
2) Allopurinol and hypoxanthine: both compete inactive. ions: by addition of
on xanthine oxidase that oxidizes hypoxanthine - Effect of EDTA.
into xanthine then to uric acid.. noncompetitive 5. Inhibition by
3) Dicumarol & Warfarin and vitamin K: both inhibitor on Vmax and phosphorylation and
compete for the catalytic site of epoxide K: dephosphorylation
reductase enzyme. a) Vmax is decreased. 6. Cyanide and carbon
- Effect of competitive inhibitor on Vmax and b) Km is unchanged. monoxide inhibit
Km: cytochrome oxidase.
a) Effect on Vmax: A competitive inhibition does
not affect Vmax.
b) Effect on K: A competitive inhibition increases
the Km of substrate.

DR. Mahmoud Ettaweel 01004486188 68

 Regulation of enzyme activity
Enzyme activity is regulated by many mechanisms.
A. Allosteric regulation of enzyme activity:
1. Allosteric enzymes generally catalyze the irreversible steps in metabolic pathways.
2. The term allosteric means “other site”, It indicates that a molecules called effectors (also
called modifiers or modulators) can bind non-covalently at a site other than active site.

a) Effectors are positive if they stimulate catalytic reaction and negative if they inhibit the
reaction.
b) Effectors may be the end product of a metabolic pathway. If it inhibits the reaction
(negative regulation), it is called: feedback inhibition.
B. Feedback inhibition:
It means that the end product of a series of reactions directly inhibits the first enzyme of that
series.

C. Feedback regulation:
It means that the end product of a series of reactions has no inhibitory effect on the first enzyme.
It rather affects the gene(s) that code for the formation of that enzyme preventing its synthesis
D. Covalent modification: phosphorylation / dephosphorylation:
1. Some enzymes may be regulated by covalent modification, most frequently by the addition or
removal of phosphate groups from the enzymes.
2. Phosphorylation reactions are catalyzed by a family of enzymes, called: protein kinase. It
utilizes ATP as a phosphate donor.
3. Phosphate groups are removed from Phosphorylated enzymes by the action of
phosphoprotein phosphatase

DR. Mahmoud Ettaweel 01004486188 69

 Isoenzymes
- Definition: Isoenzymes are different molecular forms of the enzyme that activate the same
reaction, use the same coenzyme and same substrate but they are different in chemical protein
structure. This leads to:
1. Different immunological reactions.
2. Different Km and Vmax.
3. Different physical properties.
- Example:
1. Lactate dehydrogenase enzyme (LD)
- Is a tetramer i.e. contains 4 polypeptide chains. These 4 chains are a mixture of different
proportions of 2 chains H and M (H. after heart & M after muscle).
- There are 5 isoenzymes of LD enzyme having a Diagnostic importance:
Determination of different isoenzymes helps in diagnosis of diseases e.g.
Serum LDI1 increases in certain heart
LDI1 HHHH Heart
diseases (myocardial infarction).
LDI2 HHHM Red cells Acute leukemia
LDI3 HHMM Lungs Acute leukemia
LDI4 HMMM Other tissues
Serum LDI5 increases in certain liver
LDI5 MMMM Liver
diseases (infective hepatitis)
2. Creatine kinase (CK) (CPK):
- CK-BB: in brain.
- CK-MB: in Skeletal muscle.
- CK-MM: in myocardium.
3. Isocitrate dehydrogenase: (cytosolic & mitochondrial)
4. Phosphodiesterases: 1-5

CLINICAL IMPORTANCE OF ENZYMES

A- Diagnosis of diseases
- Enzymes are intracellular and when there is cellular damage, they are released into the circulation
- The measurement of these enzymes in the serum can be used in the diagnosis of certain diseases.
• Enzymes in plasma are classified into:
A. Functional plasma enzymes: These are enzymes present normally in blood to perform
certain physiological functions. They are characterized by:
1. They are synthesized in the liver.
2. They are present in blood in higher concentration than tissues.
3. Their substrates are present in the circulation.
- Examples: Proenzymes of blood clotting, lipoprotein lipase.
B. Non-functional plasma enzymes: These enzymes are present in a very low concentration in
blood due to tissue turn over and increases in case of tissue damage.
They are characterized by:
1. They perform no physiological function in blood,
2. Their substrates, are absent from blood.
3. Their level is normally low and they increase in tissue damage
- Examples: for these enzymes are:

DR. Mahmoud Ettaweel 01004486188 70

 1. Alkaline phosphatase: increases in obstructive jaundice, hyperparathyroidism, rickets and
metastatic carcinoma to bone.
2. Transaminases:
- Aspartate aminotransferase (AST) or glutamic oxaloacetic transaminase (GOT)
increases in heart disease.
- Alanine aminotransferase (ALT) or glutamic pyruvic transaminase (GPT)
increases in liver diseases.
B- TUMOR MARKERS:
• Definition of tumor markers:
- Tumor markers are macromolecules mostly proteins whose appearance or changes in
concentration in blood or other body fluids is indicative to the presence, extent or progress
of a malignant tumor.
- Tumor markers may be tumor antigens, hormones or enzymes.
- Alterations of serum enzymes in malignancy may be due to:
1. Production of increased amounts of enzymes by tumor cells.
2. Release of intracellular enzymes due to cell damage.
• Enzymes used as tumor markers:
1. Alkaline phosphatase (ALP). It increases in bone metastasis.
2. Creatine kinase (CK): The isoenzyme fraction of the brain (CKBB) diagnose breast tumors,
prostatic carcinoma, colonic cancer, and transitional cell carcinoma of bladder.
3. Lactic dehydrogenase (LDH). It is generally increased in malignancy.

- Also decreased level of some enzymes can be used to diagnose inborn errors of metabolism e.g.
1.Glucose-6-phopshate dehydrogenase in Favism.
2.Galactosyl transferase in galactosemia
C- Treatment of diseases:
• Enzymes are used in treatment of some diseases e.g.
1. Fibrinolysins in treatment of infarctions (streptokinase).
2. Digestive enzymes in treatment of maldigestion.
3. α-chymotrypsin for treatment of intraocular haemorrhage.

MCQ
8. Which of the following causes a conformational change to the active site of an enzyme?
a- Proteolytic cleavage. b-Allosteric inhibitor.
c- Coenzymes. d- Competitive inhibitor.
9. In ………….. inhibition, the inhibitor is an end product of the enzyme action
a- Non-competitive b- Allosteric
c- Competitive d- Feed back
10. The Km value of an enzyme is:
a- The substrate concentration at half maximal velocity.
b- Half the substrate concentration at maximal velocity.
c- Dissociation constant of enzyme-substrate complex.
d- The total enzyme concentration.

DR. Mahmoud Ettaweel 01004486188 71

 MCQ
11. In a competitive inhibition:
a- Km is increased and Vmax is increased. b- Km is decreased and Vmax is normal.
c- Km is increased and Vmax is normal. d- Km is decreased and Vrnax is increased.
12. All Of the following are true as regards isoenzymes
a- They have identical polypeptide chains. b- They have different affinities to the substrate.
c- They can be separated by electrophoresis. d-lhey are present in different cells.
13. Digestive enzymes belong to the class of:
a- Hydrolases. b- Ligases. c- Lyases. d- Oxidoreductases.
14. Concerning allosteric effectors:
a- Allosteric effectors are usually analogs of that substrate.
b- The allosteric site of an enzyme is distinct from its substrate binding site.
c- Allosteric effectors cause denaturation of the enzyme.
d- Allosteric effectors cause non conformational changes in the enzyme.
15. Which of the following metalloenzymes contain copper?
a- Superoxide dismutase b- Tyrosinase
c- Glutathione peroxidase d- Cytochrome oxidase
16. The enzyme:
a- Reduces the energy of activation. b- Increases total energy of substrate.
c- Increases the equilibrium constant. d- Decreases total energy of the product.
17. In competitive inhibition:
a- Inhibitor has structural similarity to substrate
b- Km is decreased
c- Vmax is decreased
d- Reaction rate is independent of substrate concentration
18. As regards lactate dehydrogenase, all are correct EXCEPT:
a- It is formed of four subunits. b- isoenzyme 5 increases in plasma in liver diseases.
c- there are 6 isoenzymes. d-isoenzyme I increases in plasma in myocardial infarction.
19. In inhibitors:
a- Km increases. b- Km decreases. c- Vmax decreases. d- All Of the above.
20. Elevation of the blood level of the following enzyme helps in the diagnosis of hepatitis:
a- Amylase b- Alanine transaminase c- Creatine Kinase d- Acid phosphatase
21. Isozymes are enzymes with different amino acid sequences but the same:
a- Tissue.
b- Function.
c- Quaternary structure.
d- Electrophoretic pattern.

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74 CARBOHYDRATES METABOLISM

INTRODUCTION TO METABOLISM
- Humans and all living organisms are in a steady dynamic state.
- This is maintained by the free energy obtained from the oxidation of nutrients through the
different metabolic pathways.

- The objectives of this chapter are:

1. To understand the different forms of energy.
2. To know the amount of energy stored in different types of chemical bonds.
3. To know how chemical energy is generated, transferred and stored by living cells.

METABOLISM
Metabolism means the series of biochemical reactions that occur for biomolecules in living
organisms.
It is classified into: anabolism and catabolism.

ANABOLISM
- Means synthesis of macromolecules from simple one. Anabolism is usually endergonic (consumes
energy).
Examples
- Synthesis of polysaccharides from monosaccharides.
- Synthesis of triacylglycerol from glycerol and fatty acids.
- Synthesis of proteins from amino acids.

CATABOLISM
Means breakdown of macromolecules into simplest components. It is usually exergonic (release
energy).
- Catabolism of the main metabolites occurs in 4 stages:

- In stage 1, metabolic fuels are hydrolyzed in the gastrointestinal tract to a diverse set of
monomeric building blocks (glucose, amino acids, and fatty acids) and absorbed.
- In stage 2,
- THE building blocks are degraded by various pathways in tissues to a common metabolic
intermediate, ACETYL-COA.
- Most of the energy contained in metabolic fuels is conserved in the chemical bonds
(electrons) of acetyl-CoA.
- A smaller portion is conserved in reducing nicotinamide adenine dinucleotide (NAD) to
NADH+H or flavin adenine dinucleotide (FAD) to FADH2.
- Reduction indicates the addition of electrons that may be free, part of a hydrogen atom
(H), or a hydride ion.
- In stage 3, the citric acid (Krebs, or tricarboxylic acid ‘TCA’) cycle oxidizes acetyl-CoA to CO2.
The energy released in this process is primarily conserved by reducing (NAD) to NADH+H or
(FAD) to FADH2.
- The final stage is oxidative phosphorylation, in which the energy of NADH+H and FADH2 is
released via the electron transport chain (ETC) and used by an ATP synthase to produce
ATP. This process requires O2.

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 CARBOHYDRATES METABOLISM 75

METABOLIC ENERGY STORAGE

- ATP is a form of circulating energy currency in cells. It is formed in catabolic pathways by
phosphorylation of ADP and may provide energy for biosynthesis (anabolic pathways). There is
a limited amount of ATP in circulation.
- Most of the excess energy from the diet is stored as glycogen and fatty acids. Although proteins
can be mobilized for energy in a prolonged fast, they are normally more important for other
functions (contractile elements in muscle, enzymes, etc.).

LOW AND HIGH-ENERGY BONDS

LOW-ENERGY BONDS HIGH-ENERGY BONDS
yields < 7.3 Kcal/mol on hydrolysis. yields > 7.3 Kcal/mol.
Examples of low energy bonds 1- Phosphate bonds
• Ester bonds (Phosphate ester) • Phosphoenolpyruvate.
• Glycosidic bonds (oligo, polysaccharides) • Carbamoyl phosphate
• Peptide bonds. • Creatine phosphate
• Pyrophosphate as ADP and ATP
• 1,3 Bisphosphoglycerate
2- Sulfur bonds
• Active methionine: SAM
• Thioester as acetyl COA
• B-Ketoacyl-CoA as: Acetoacetyl-Co

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76 CARBOHYDRATES METABOLISM

REDOX REACTION
Oxidation accompanied by reduction called redox reaction

OXIDATION REDUCTION
1- Addition of oxygen 1. Removal of oxygen
2. Removal of hydrogen 2. Addition of hydrogen
3. Loss of electron increase in positive charge. 3. Addition of electrons
.

Redox potential
Electron Affinity
Hydrogen is transferred through different component of redox chain so energy liberated is gradual
DEFINITION
Affinity of a substance for electron (its electronegativity) compared with hydrogen.
- Hydrogen has lowest electron affinity
- Oxygen has highest electron affinity.
- All other substances lie between O2 and H+.
NB. Hydrogen atom formed of one electron and one proton
REGULATION OF FUEL METABOLISM
- The pathways that are operational in fuel metabolism depend on the nutritional status of the
organism. Shifts between storage and mobilization of a particular fuel, as well as shifts among
the types of fuel being used, are very pronounced in going from the well-fed state to an
overnight fast, and finally to a prolonged state of starvation. The shifting metabolic patterns
are regulated mainly by the insulin/glucagon ratio.
- Insulin is an anabolic hormone that promotes fuel storage. Its action is opposed by a number of
hormones (anti insulin hormones), including (glucagon, epinephrine, cortisol, and growth
hormone).
- The major function of glucagon is to respond rapidly to decreased blood glucose levels by
promoting the synthesis and release of glucose into the circulation.
- Anabolic and catabolic pathways are controlled at three important levels:
- Allosteric inhibitors and activators of rate-limiting enzymes.
- Feedback inhibition.
- Feedback regulation “Control of gene expression” by insulin, glucagon and substrate.
Phosphorylation by (glucagon) through (Kinase) and de

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FATE OF GLUCOSE

Oxidation Storage Conversion

‫احرقه لو محتاج‬ ‫أو أخزنه يف التالجات‬ ‫أو أحوله لحاجات‬

Major Minor
pathway pathway

Glycolysis
- pentose
Pyruvate As glycogen by glycogenesis in e.g. - To lipid by lipogenesis
phosphate
Liver and Muscles or - To ptn
pathway
Acetyl Co-A
Or
- Uronic acid
Krebs cycle
pathway
R. chain

CHAPTER MAP

Glucose Galactose Fructose

Metabolism Metabolism Metabolism
Feeding state Fasting state
‫واحنا واكلي‬
‫واحنا صايمي‬
‫هيكون يف انسولي‬ 1- Conversion of
Glucose to
1- Glycolysis Galactose
Glucose pyruvate 1- Catabolism
2- Pyruvate A. Co-A 2- Conversion of
3- Krebs cycle Galactose to 2- Conversion
NADH+H+ & FADH2 Glucose of Fructose
1- Glycogenolysis to Glucose
4- Respiratory chain
ATP 3- Lactose
2- Gluconeogenesis 3- Ds
5- Minor pathways synthesis
PPP &UAP
6- Glycogenesis 4- Ds
7- Lipogenesis
See lipid Metabolism

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GLYCOLYSIS (EMBDEN MEYERHOF PATHWAY)

DEFINITION
Breakdown of glucose into 2 molecules of pyruvate aerobically (in the presence O2)
or 2 molecules of lactate an aerobically (in the absence of O2).

SITE
Cytosol of all tissue cells

STAGES OF GLYCOLYSIS
1. Stage one (the energy requiring stage):
a) One molecule of glucose is converted into two molecules of glyceraldehyde-3- phosphates
b) This step requires 2 molecules of ATP (energy loss)
2. Stage two (the energy producing stage):
a) The 2 molecules of glyceraldehyde-3-phosphate are converted into pyruvate (aerobic
glycolysis) or lactate (anaerobic glycolysis)
STEPS

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BIOLOGICAL IMPORTANCE (FUNCTIONS) OF GLYCOLYSIS
1. Energy (ATP) production of glycolysis:
ATP production = ATP produced - ATP utilized.

ATP produced ATP utilized Net

In absence 4 ATP by (Substrate level phosphorylation) 2 ATP 2
of oxygen • 2ATP from 1,3 BPG. • From glucose to ATP
(anaerobic • 2ATP from phosphoenol pyruvate glucose-6-p.
glycolysis) • From fructose-6 to
fructose1,6 bis p.
In presence 4 ATP by (Substrate level phosphorylation) 2ATP 6
of oxygen • 2ATP from 1,3 BPG. • From glucose to Or
(aerobic • 2ATP from Phosphoenol pyruvate glucose-6-p. 8
glycolysis) 6 ATP or 4 ATP • From fructose-6- p ATP
(From oxidation of 2 NADH+H+ in mitochondria). to fructose 1, 6
See later bisphosphates.

2. Oxygenation of tissues:
Through formation 2, 3 bisphosphoglycerate, this decreases the affinity of Hemoglobin to O2.

3. Provides important intermediates:

a) Dihydroxyacetone phosphate: may give glycerol-3-phosphate, which is used for synthesis of
triacylglycerols and phospholipids (lipogenesis).
b) 3-Phosphoglycerate: which may be used for synthesis of serine.
c) Pyruvate: which may be used in synthesis of amino acid alanine.

4. Aerobic glycolysis provides the mitochondria with pyruvate, which gives acetyl CoA →
Krebs’ cycle.

5. very important in: (because the glucose is the most dependent source of energy)
• Tissues with no mitochondria: mature RBCs, cornea and lens
• Tissues with few mitochondria: Testes, leucocytes, medulla of the kidney, retina, skin and
gastrointestinal tract.
• Tissues undergo frequent oxygen lack: skeletal muscles especially during exercise

6. Functions of glycolysis in RBC:

1. Mature RBCs contain no mitochondria thus:
a) They depend only upon glycolysis for energy production (=2 ATP).
b) Lactate is always the end product.
2. Glucose uptake by RBCs is insulin independent.
3. Reduction of met-hemoglobin: Met-hemoglobin binds oxygen irreversibly. Glycolysis
produces NADH+H, which used for reduction of met-hemoglobin in red cells, into
hemoglobin. This reaction is catalyzed by “cytochrome b5-met-haemoglobin reductase”
system (cyt b5).

Met-HB NADH+H HB

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4. 2,3 Bisphosphoglycerate (2,3 BPG):

a) The RBCs have the ability to form 2, 3 bisphosphoglycerate (2, 3 BPG) through what is
called: (Rapoport-Luebering cycle) or (2, 3 bisphosphoglycerate cycle).
2, 3 BPG ↓ affinity of hemoglobin to O2 → Good oxygenation of tissues.
b) Mechanism:
In the erythrocytes of many mammalian species the reaction

DIFFERENCES BETWEEN AEROBIC AND ANAEROBIC GLYCOLYSIS

Aerobic Anaerobic
End product Pyruvate Lactate
Energy 6 or 8 ATP 2 ATP
Regeneration of NAD Through respiratory chain in Through lactate formation
mitochondria
Availability to TCA in Available and 2 pyruvate can Not available as lactate is
mitochondria oxidize to give 30 ATP cytosolic substrate

IMPORTANCE OF LACTATE PRODUCTION IN ANAEROBIC GLYCOLYSIS:

▪ In absence of oxygen, NADH+H+ is not oxidized by the respiratory chain, thus: The conversion
of pyruvate to lactate is the mechanism for regeneration of NAD.
This helps continuity of glycolysis, as the generated NAD will be used once more for oxidation of another
glucose molecule.

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Regulation of glycolysis
The rate of glycolysis is regulated by controlling of the three irreversible enzymes (key enzymes).
These enzymes catalyze what is called committed reactions of the pathway.
These enzymes are: Glucokinase (Hexokinase), phosphofructokinase-1 and pyruvate kinase.

Glucokinase Hexokinase
Site Liver only All tissue cells
Affinity to Low affinity (high km) i.e. it acts High affinity (low km) i.e. it acts even in
glucose only in the presence of high the presence of low blood Glucose
Glucose blood concentration. concentration.
Substrate Glucose only Glucose, galactose and
fructose
Effect of Induces synthesis of No effect
insulin Glucokinase
Effect of No effect Allosterically inhibits Hexokinase
glucose-6-
phosphate
Function Acts in liver after meals. It It phosphorylates glucose inside the body
removes glucose coming in cells. This makes glucose concentration
portal circulation, converting it more in blood than inside the cells
into glucose-6-phosphate This leads to continuous supply of glucose
for the tissues even in the presence of low
blood glucose
▪ Hormonal regulation:
a) Insulin: Stimulates synthesis of all key enzymes of glycolysis. It is secreted after meal (in
response to high blood glucose level).
b) Glucagon: Inhibits the activity of all key enzymes of glycolysis. It is secreted in response to low
blood glucose level.
▪ Energy regulation:
a) High level of ATP inhibits PFK-1
and pyruvate kinase.
b) High level of ADP and AMP
stimulate PFK-1.
Substrate regulation:
a) Glucose-6-phosphate inhibits
Hexokinase (and not Glucokinase).
b) Fructose 2, 6 bisphosphate
stimulates PFK-1.
c) Citrate inhibits PFK-1.
d)Fructose 1,6 bisphosphate
stimulates pyruvate kinase.

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▪ Fructose 2, 6 bisphosphate:
a) This substrate is produced from fructose-6-
phosphate by reaction catalyzed by:
phosphofructokinase-2 (PFK-2) enzyme.
b) Fructose 2, 6 bisphosphate stimulates glycolysis by
allosteric stimulation of PFK-1. It also inhibits
gluconeogenesis by inhibiting fructose 1, 6
bisphosphatase enzyme.

Clinical aspects of glycolysis:

There are many diseases associated with impaired
glycolysis they include:
▪ Pyruvate kinase (PK) deficiency:
a) This leads to excessive hemolysis of RBCs → leading
to hemolytic anemia.
b) Genetic deficiency of PK enzyme causes decrease
the rate of glycolysis and decrease production of ATP.
c) ATP is required for Na-K ATPase, which is important
for stability of RBCs.

▪ Hexokinase deficiency:
It leads to hemolytic anemia due to decrease ATP
production.
The mechanism is similar to that of PK deficiency.

▪ Lactic acidosis:
Definition: It is the lowered blood pH and bicarbonate
levels due to increased blood lactate above normal
level.
Mechanism: This depletes bicarbonate → ↓pH of
blood → Lactic acidosis may lead to coma.
Causes: It results from increased formation OR decreased utilization of lactate.
1) Increased formation of lactate: as in severe muscular exercises.
2) Decreased utilization of lactate in tissues: if occurs in cases of anoxia or lack of oxygen e.g.
myocardial infarction, respiratory disorders and anemia.
3) Phenformin: is oral hypoglycemic drug causing excessive anaerobic oxidation of glucose and excess
lactate production.

Lactate
a) Sources: From glycolysis especially in RBCs due to absence of mitochondria and Muscle
during exercises due to oxygen lack
b) Fate:
1) Glucose formation: [through lactic acid cycle (Cori cycle)]:
- Lactate formed in muscles and RBCs may diffuse to the blood then to the liver.
- In the liver, lactate is converted to glucose by gluconeogenesis. Glucose may diffuse
back to the blood, then to red cells or muscles to be used for production of energy.
2) Conversion into pyruvate: If oxygen gets available, lactate is converted into pyruvate,
which proceeds into Kreps cycle
3) Lactate may be accumulated in muscles causing muscle fatigue.
4) Lactate is excreted in urine and sweat

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Definition of Cori cycle: It is the conversion of glucose into lactate in peripheral tissues.
Followed by conversion of lactate into glucose in liver.

Lactate dehydrogenase
1. It is an enzyme which catalyzes the reaction: Lactate ↔ Pyruvate
2. This reaction helps the re-oxidation of NADH+H into NAD.
3. It has 5 isoenzymes: LD1, LD2, LD3, LD4 and LD5.
4. Medical importance:
Estimation of the activity of lactate dehydrogenase enzyme in plasma helps the diagnosis of heart
and liver diseases:
a) LD1: Elevated in some heart diseases e.g. myocardial infarction.
b) LD5: Elevated in some liver diseases as acute viral hepatitis.

In vitro inhibition of glycolysis

1- Arsenate: by competing with inorganic phosphate in the reaction:
gIyceraidhyde-3 -p → 1,3 bisphosphoglycerate
2. Iodoacetate: by inhibiting glyceraldhyde-3-p dehydrogenase.
3. Fluoride: Inhibits enolase enzyme. Clinical laboratories use fluoride to inhibit glycolysis by
adding it to the blood before measuring blood glucose.

MITOCHONDRIAL PATHWAY FOR GLUCOSE OXIDATION

o Complete oxidation of glucose occurs in both Cytosol (glycolysis) and mitochondria (Krebs’
cycle).
o In the presence of O2, pyruvate (the end product of glycolysis) passes by special pyruvate
transporter into mitochondrion which proceeds as follows:
Oxidative decarboxylation of pyruvate to Acetyl-COA.
Acetyl CoA is then oxidized completely to CO2, H2O through Krebs’ cycle

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OXIDATIVE DECARBOXYLATION OF PYRUVATE TO ACETYL COENZYME A (= ACETYL COA)

▪ Enzyme: Pyruvate dehydrogenase (PDH) complex:
a) Structure: contains 3 subunits, which catalyzes the reaction in 4 steps. These subunits are:
pyruvate decarboxylase, dihydrolipoyl transacetylase and dihydrolipoyl dehydrogenase.
b) Coenzymes: needs 5 coenzymes (all are vitamin B complex derivatives):
1) Vitamin B1 = Thiamin pyrophosphate = TPP.
2) Lipoic acid
3) Coenzyme A = CoASH.
4) Flavin adenine dinucleotide = FAD.
5) Nicotinamide adenine dinucleotide = NAD+.
c) Location: PDH is located within the mitochondrial matrix.
▪ Reactions:

▪ Energy production: → NADH+H (through respiratory chain) →3ATP

▪ Regulation of oxidative decarboxylation (PDH):
a) PDH exists in two forms: Phosphorylated (inactive) and dephosphorylated (activated).
- PDH kinase enzyme converts active into inactive PDH enzyme.
In vitro inhibition of PDH:
a) Arsenic. b) Thiamin (B1) deficiency

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MCQ
1. The product of glycolysis in erythrocytes is:
a- NADPH b- Lactate c- Pyruvate d- Carbon dioxide
2. Glucokinase is more active after a meal, because:
a- It is an inducible enzyme. b- It has more affinity to glucose than hexokinase
c- It is present in all tissues d- Can act on all monosaccharides
3. An example of substrate level phosphorylation is:
a- Isocitrate Dehydrogenase b- Enolase
c- Pyruvate kinase d- Glyceraldehyde-3-phosphate dehydrogenase
4. Which enzyme catalysis an irreversible reaction?
a- Transketolase b- Phospho fructokinase
c- Aldolase d- Glyceraldehyde-3-phosphate dehydrogenase
5. Which enzyme in glycolytic pathway is inhibited by fluoride ions?
a- Hexokinase b- phosphofructokinase c- Aldolase d- Enolase
6. During anaerobic glycolysis NAD+ is regenerated from NADH by:
a- Glyceraldehyde-3-phosphate dehydrogenase b- Oxygen
c- Glutamate dehydrogenase d- Lactate dehydrogenase
7. All the enzymes listed below are regulatory enzymes, EXCEPT:
a- Glycogen phosphorylase b- Glucose-6-phosphate dehydrogenase
c- Pyruvate kinase d- Lactate dehydrogenase
8. ATP is generated in all the following reactions EXCEPT:
a- Glyceraldehyde-3-phosphate dehydrogenase b- I ,3-bisphosphoglycerate kinase
c- Pyruvate kinase d- Hexokinase
9. The key enzyme of glycolysis is:
a- Glucose-6-phosphatase b- Glyceraldehyde-3-phosphate dehydrogenase
c- Phosphohexose isomerase d- Phosphofructokinase
10. Catalytic activity of phosphofructokinase is increased by:
a- AMP c- ATP b- Fructose-I ,6-bisphosphate d- Fructose-I -phosphate
11. Complete Oxidation of one molecule of glucose yields how many ATPs?
a- 12 b- 24 c. 38 d. 129
12. All the following coenzymes are involved in the pyruvate dehydrogenase reaction
EXCEPT:
a. Thiamine pyrophosphate (TPP) b- Biotin c- NAD+ d- FAD
13. There is no net synthesis of glucose from fatty acids, because of the irreversible nature
of the reaction:
a- Pyruvate to oxaloacetate b- Pyruvate to acetyl COA
c- Phosphoenol pyruvate to pyruvate d- Oxaloacetate to Phosphoenol pyruvate
14. Pyruvate is converted to acetyl COA by:
a- Pyruvate dehydrogenase b- Pyruvate carboxylase
c- Pyruvate kinase d- Lactate dehydrogenase
15. In glycolysis, the following reactions are irreversible, EXCEPT that catalyzed by:
a- Glucokinase. b- Phosphoglycerate kinase. c- PFK-1 d- Pyruvate kinase.
16. Phosphoglycerate kinase catalyzes conversion of BPG into:
a-2,3 BPG. b- 2-phosphoglycerate. c- 3-phosphoglycerate. d- Non of the above.

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KREBS’ CYCLE
Citric acid cycle (CAC), tricarboxylic acid cycle (TCA) or Catabolism of acetyl CoA

DEFINITION series of reactions in which acetyl CoA is oxidized into CO2, H2O and energy.
LOCATION Mitochondria
STEPS
Citrate Is Krebs' Starting Substrate For Making Oxaloacetate.

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 CARBOHYDRATES METABOLISM 87
ENERGY PRODUCTION OF TCA:
Enzyme Method of ATP production No. of ATP
Isocitrate Oxidation of NADH+H+ by respiratory chain 3 ATP
dehydrogenase
α-Ketoglutarate Oxidation of NADH+ H+ by respiratory chain 3 ATP
DH
Succinyl CoA Substrate level phosphorylation 1 ATP
thiokinase
Succinate Oxidation of FADH2 by respiratory chain 2 ATP
dehydrogenase
Malate Oxidation of NADH+H+ by respiratory chain 3 ATP
dehydrogenase
Total = 12 12 ATP

FUNCTIONS (SIGNIFICANCE) OF TCA: TCA CYCLE IS AMPHIBOLIC

I.e. it has catabolic (breakdown) and anabolic (formation) functions.
▪ Energy: 12 ATP
▪ Catabolic functions: Oxidation of carbohydrate, lipids and proteins.
▪ Anabolic functions: Formation of:
✓ Amino acids: α-Ketoglutarate Transamination Glutamate.
✓ Glucose: α-Ketoglutarate Gluconeogenesis Glucose.
✓ Heme synthesis: Succinyl CoA → Heme.
✓ Fatty acid and cholesterol.
✓ CO2: is used in the (CO2 fixation reactions) (carboxylation reactions) :
o Requirements: 1- Enzyme: carboxylase. 2- Co-enzyme: Biotine
3- CO2 4- ATP
o Important Reactions:
• CHO: Pyruvate + CO2 → Oxaloacetate Gluconeogenesis Glucose.
• Lipid: Acetyl COA + CO2 → Malonyl CoA → Fatty acids.
• Ptn: Ammonia + ATP + CO2 → Carbamoyl phosphate → Urea and pyrimidines.
• Propionyl CoA + CO2 → Methyl malonyl CoA → Succinyl CoA → Intermediate of citric acid cycle.
• Formation of C6 of purines.

IN VITRO INHIBITION OF TCA CYCLE:

a) Fluoroacetate (F1- CH2-COSCoA): inhibits aconitase enzyme.
b) Arsenate: inhibits α-Ketoglutarate dehydrogenase enzyme.
c) Malonic acid: inhibits Succinate dehydrogenase enzyme (competitive inhibition.

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REGULATION OF CITRIC ACID CYCLE

TCA is regulated through the key enzymes (citrate synthase, Isocitrate DH and
α-Ketoglutarate DH) and the availability of CO2
a) Citrate synthase
1) Stimulated by: acetyl CoA, oxaloacetate, ADP and NAD.
2) Inhibited by: long chain acyl CoA, citrate, Succinyl CoA, ATP and NADH+H+
b) Isocitrate dehydrogenase and α-Ketoglutarate dehydrogenase:
1) Stimulated by: NAD, ADP.
2) Inhibited by: NADH+H+ and ATP.
c) Availability of Oxygen: Citric acid cycle needs oxygen to proceed. This is because in absence of
oxygen, respiratory chain is inhibited leading to increase NADH+H+ → inhibition of TCA cycle.

SOURCES AND FATE OF OXALOACETATE

a) Sources of oxaloacetate:
1) Oxidation of Malate.
2) Transamination of Aspartate:
3) Carboxylation of pyruvate
4) Cleavage of citrate
b) Fate of oxaloacetate:
1) Formation of citrate:
2) Reduction to Malate.
3) Transamination into aspartate

SOURCES AND FATE OF PYRUVATE

Sources Fate
1. Glucose: glycolysis. 1. Glucose formation: gluconeogenesis.
2. Lactate: by lactate DH 2. Lactate formation: by lactate DH.
3. Malate: by malic enzyme. 3. Malate formation: by malic enzyme.
4. Alanine: by transamination. 4. Alanine formation: by transamination.
5. Serine: by non-oxidative 5. Oxaloacetate formation:
deamination. by pyruvate carboxylase.
6. Other amino acids: methionine

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 CARBOHYDRATES METABOLISM 89

MCQ
17. How many ATPs are generated per one rotation of the citric acid cycle?
a- 2 b- 8 c- 12 d- 15
18. The following reaction produces ATP at the substrate level:
a- PFK-1 b. Aldolase. c. Phosphoglycerate kinase. d- Glycaaldehyde-3P dehydrogenase.
19. Oxidation of glucose in RBCs gives:
a- 2ATP. b- 3 ATP. c- 8 ATP. d. None of the
20. PFK-1 is inhibited by all. EXCEPT:
a- ATP b- Citrate. c. Glucagon. d- AMP
21. Conversion of glucose phosphate to fructose-1,6 bisphosphate requires:
a- Phosphoglucomutases and phosphorylase. b-Phosphoglucomutases and aldolase.
c. Phosphohexose and phosphofructokinase
d. Phosphoglucomutases and phosphofructokinase- 1
22. Pyruvate can be converted to :
a- Lactate b- Nanine c- Oxaloacetate. d. All of the above.
23. Pyruvate dehydrogenase complex, requires all,
a- NAD. b- COA. C- ATP d- Pyruvate.
24. All the following correctly pairs coenzyme with its enzyme, EXCEPT:
a- Succinate dehydrogenase, FAD. b- Malate dehydrogenase NAD.
c- Acetyl COA carboxylase, biotin. d- Pyruvate dehydrogenase PLP.
25. Oxidative decarboxylation of a-ketoglutarate requires an, EXCEPT:
a- FAD b- COASH. c. PLP. d- Lipoate
26. In TCA cycle the only enzyme which requires FAD is:
a- Iso-citrate dehydrogenase. b- a-ketoglutarate dehydrogenase.
c- Succinate dehydrogenase. d- Malate dehydrogenase.
27. All of the following are Krebs' cycle intermediates, EXCEPT:
a- Acetoacetate. b- Cis aconitate. c. Succinate d- Fumarate.
28. The release or carbon dioxide results from the following reaction of the citric acid
cycle:
a- Citrate to isocitrate. b-Fumarate to malate.
c- Malate to oxaloacetate. d- Isocitrate to a-ketoglutarate.
29. In pyruvate kinase (PK) deficiency, hemolysis of red cells occurs primarily because of
increased intracellular levels of:
a- Lactate. b- Pyruvate.
c- ADP to ATP ratio. d- 2,3-diphosphoglycerate.

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OXIDATION OF EXTRA MITOCHONDRIAL NADH+H+

1. The molecules of cytosolic NADH+H+ cannot penetrate mitochondrial membrane; however,
they can be used to produce energy by respiratory chain phosphorylation in the mitochondria.
2. This can be done by using special carriers for hydrogen of NADH+H+ these carriers are either
(Glycerophosphate shuttle) or (Aspartate - Malate shuttle).

GLYCEROPHOSPHATE SHUTTLE
- It is important in certain muscles and nerve cells.
- The final energy produced is 2 x 2 ATP → 4 ATP.
- Mechanism:
-The coenzyme of cytosolic (glycerol -3- phosphate DH) is NAD+.
-The coenzyme of mitochondrial (glycerol -3- phosphate DH) is FAD.

MALATE - ASPARTATE SHUTTLE

- It is important in tissues particularly liver and heart.
- The final energy produced is 2 x 3 ATP → 6 ATP
- Mechanism:
- The coenzyme of cytosolic and mitochondrial (Malate dehydrogenase) is NAD+

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RESPIRATORY CHAIN
(ELECTRON TRANSPORT CHAIN)
DEFINITION
It is the final common pathway in aerobic cells by which electrons derived from various
substances are transferred to oxygen to form water.
SITE
Mitochondria in all over body cells except: (RBC, cornea).

ORGANIZATION OF THE RESPIRATORY CHAIN

- The inner mitochondrial membrane contains 5 fixed enzyme complexes, called complex I, II, Ill,
IV and V. Complex V catalyses ATP synthesis.
a) Each complex accepts or donates electrons to relatively 2 mobile electron carriers such as
coenzyme Q and cytochrome C.
b) Each carrier of electron transport chain can receive electrons from the more electronegative
donor to the next more electropositive carrier in the chain.
- Finally electrons combine with oxygen and protons to form water.

COMPONENT
a) Complex I: Contains an enzyme called (NADH dehydrogenase)
(i) Its coenzyme is FMN.
(ii) It contains several iron and sulfur atoms.
(iii) It oxidizes NADH+H into NAD. And converts its coenzyme FMN into FMNH 2.
b) Complex II: Contains an enzyme called: (flavoprotein dehydrogenase) e.g.
Succinate dehydrogenase of TCA and acyl COA dehydrogenase of fatty acid oxidation.
(i) Its coenzyme is FAD.
(ii) It contains iron and sulfur atoms.
c) Complex Ill: contains an enzyme cytochrome b.
d) Complex IV: contains cytochromes a + a3
e) Complex V: catalysis ATP synthesis

REACTIONS OF RESPIRATORY CHAIN

1. Entry via NADH + H+: NADH + H+ obtained from reactions catalyzed by dehydrogenase enzymes
e.g. dehydrogenase of TCA can join the chain giving electrons to FMN of complex I to
coenzyme Q, to cytochrome b, cytochrome c to cytochrome a + a3 to the final acceptor O 2.
2. Entry via FADH2: FADH2 obtained from reactions catalyzed by flavoprotein dehydrogenase e.g. Succinate
dehydrogenase can join the chain directly giving electrons to coenzyme Q, then to cytochrome b, c, a +
a3 to the final acceptor O2.

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‫‪STEPS‬‬

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 CARBOHYDRATES METABOLISM 93
OXIDATIVE PHOSPHORYLATION
A. Introduction:
1. Electrons are transferred down the respiratory chain from NADH to oxygen. This is because
NADH is a strong electron donor, while oxygen is a strong electron acceptor.
2. The flow of electrons from NADH to oxygen (oxidation) results in ATP synthesis by
phosphorylation of ADP by inorganic phosphate “Pi” (phosphorylation). Therefore, there is a
coupling between oxidation and phosphorylation.
Two theories explain the ATP synthesis, (chemiosmotic hypothesis) and (membrane transport
system).
B. Chemiosmotic hypothesis: (Mitchell hypothesis).
- This hypothesis is one form of oxidative phosphorylation. It can be summarized as follows:
1. Proton pump:
a. The transport of electrons down the respiratory chain → Gives energy.
b. This energy is used to transport H+ from the mitochondrial matrix → across inner
mitochondrial membrane → inter membrane space.
c. This is done by complexes I, lll and IV.
d. This process creates across the inner mitochondrial membrane:
i. An electrical gradient: (with more positive charges on the outside of the
Membrane than on the inside)
ii. A pH gradient: (the outside of the membrane is at lower pH than the inside).
e. The energy generated by Hits proton gradient is sufficient for ATP synthesis.
2. ATP synthase (complex V):
In the inner mitochondrial membrane, there is a phosphorylating enzyme complex: ATP
synthase (or complex V).
a) It is formed of 2 subunits:
(I) F1 subunit which protrude into matrix.
(ii) Fo subunit which present in the membrane.
b) The protons outside the inner mitochondrial membrane can re-enter the mitochondrial
matrix by passing through channel (Fo - F1 complex) to pass by ATP synthase enzyme
which is present in F1 subunit. This results in the synthesis of ATP from ADP + Pi. At the
same time decrease the pH and electrical gradients.

❖ Evidences support chemiosmotic theory:

a) Addition of protons (acid) to the external medium of intact mitochondria leads to the
generation of ATP.
b) ATP synthesis does not occur in soluble Cytosol system where there is no ATP synthase. A
closed membrane as mitochondria must be present in order to obtain oxidative
phosphorylation.
C) The component of respiratory chain is organized in a sided manner as required by
chemiosmotic theory.
❖ P/O ratio: It is the ratio between numbers of ADP mole changed into ATP to the number of
oxygen atom (1/2 O2) utilized by respiratory chain.
- It is 3:1 if electrons enter through NAD-coenzyme Q .
- And it is 2:1 if electrons join the chain directly at the level of coenzyme Q.

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INHIBITORS OF RESPIRATORY CHAIN

▪ Definition: Are compounds preventing the passage of electrons by binding to a component of the
chain, blocking the oxidation, reduction reaction.

Complexes Inhibited by
Complex I Barbiturates, “piericidin A” antibiotic and by the
(site 1) insecticide and fish poison “rotenone”
Complex II Carboxin
Complex III (site 2) Antimycin A and dimercaprol.
Complex IV (site 3) H2S, cyanide (CN-), carbon monoxide and sodium
azide.
Complex V Oligomycin

UNCOUPLERS OF RESPIRATORY CHAIN

▪ Definition: These are substances that allow oxidation to proceed but prevent phosphorylation. So
energy released by electron transport will be lost in the form of heat. This explains the cause of
hotness after intake of these substances.

Uncoupler Mechanism
Thermogenin In brown adipose tissues
Thyroxin
Oligomycin Binds to the stalk of the ATP synthase. Closes the H+ channel,
and prevent re-entry of protons to the mitochondrial matrix.
2,4 It increases the permeability of the inner mitochondrial
dinitrophenol membrane to proton causing decrease proton gradient.
Calcium and This explains the fever that accompanies toxic overdoses of
high doses of these drugs.
aspirin:
lonophores : e.g. They have the ability to make a complex with cations as “K+”
antibiotic and facilitate their transport into mitochondria and other
“valinomycin” biological membranes. They inhibit phosphorylation because
they decrease both electrical and pH gradient.

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 CARBOHYDRATES METABOLISM 95

PENTOSE PHOSPHATE PATHWAY

DEFINITION
It is an alternative pathway for glucose oxidation where:
1. ATP (energy) is neither produced nor utilized.
2. Its main function is to produce NADPH+H+ and pentoses.

LOCATION
1. Intracellular location: Cytosol.
2. Organ location:
a) It is active in tissues where NADPH+H+ is needed for fatty acids synthesis.
1- Adipose tissue and liver. 2- Adrenal cortex and gonads.
3- Red cells 4- Retina
b) In many tissues: It supplies pentoses for synthesis of nucleotides.

FUNCTIONS OF HMP PATHWAY

1. Production of pentoses:
Which are essential for synthesis of nucleic acids (RNA and DNA), nucleotides as (ATP, GTP)
and coenzymes as (NAD, NADP, FAD).
2. Production of NADPH+H+:
A. Sources :
1. Pentose phosphate pathway.
2. Malic enzyme (Malate pyruvate).
3. Isocitrate dehydrogenase (cytoplasmic).
B. Fate:
1- Reductive biosynthesis.
a) CHO: uronic acid
b) Lipids: (Fatty acids, cholesterol, steroids, Bile salts).
c) Proteins: non-essential amino acids.
2- Reduction of Glutathione.
3- Reduction of retinal. 4- Reduction of Cyt P450
5- N.O synthesis 6- sphingosine & galactolipids.
7- Non-essential amino acid 8- Phagocytosis
▪ Phagocytosis by white blood cells (respiratory burst):
Def: It is the rapid consumption of molecular oxygen that accompanies the formation of
superoxide by NADPH oxidase.
- Superoxide is then converted into H2O2 by superoxide dismutase enzyme.
- H2O2 by myeloperoxidase enzyme in the presence of HCL is converted into hypochlorite
(HOCL-), which kills bacteria.

REACTIONS (STEPS)
• two phases: oxidative and non-oxidative:
1. Oxidative (irreversible) phase:
Where 3 molecules of “glucose-6-phosphate” are converted into 3 molecules of
“Ribulsose-5-phosphate” with production of NADPH+H+ and CO2.
2. Non-oxidative (reversible) phase:
Where the 3 molecules of “ribulose-5-phosphate” are interacted and converted into 2
molecules of “glucose-6-phosphate” and one molecule of “glyc-3-phosphate”.
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 CARBOHYDRATES METABOLISM 97
PENTOSE PHOSPHATE PATHWAY IN SKELETAL MUSCLES
➢ Skeletal muscles obtain their pentose requirement by reversible reactions of pentose
phosphate pathway, using fructose-6-phosphate and glyceraldehyde-3-p and the enzymes
transketolase and transaldolase. As they are poor in G-6-PDH.

DIFFERENCES BETWEEN HMP SHUNT AND GLYCOLYSIS

HMP pathway Glycolysis
Location In certain cells In all cells
Oxidation of Oxidation occurs in the first Phosphorylation occurs
glucose reaction. first then oxidation.
Coenzyme NADP NAD+
Energy No energy production 2 or 8 ATP
CO2 Produced Not produced
Pentoses Produced Not produced

REGULATION

NADP+ Insulin
+
G-6- Dehydrogenase
Glucose-6-phosphate 6-phosphogluconate
-
NADPH+H+ Acetyl COA

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98 CARBOHYDRATES METABOLISM

DEFECT OF PENTOSE PHOSPHATE PATHWAY: “FAVISM”

− Definition:
It is type of a hemolytic anemia (excessive destruction of RBCs) results after ingestion of fava
beans and some other compounds (sulfonamide, primaquine, anti-tuberculosis).
− Cause: Deficiency of glncose-6-phosphate dehydrogenase enzyme.
− CCC: “Heinz bodies”- oxidized Hemoglobin precipitated within RBCs.
− Mechanism:
a) Deficiency of glucose-6-P dehydrogenase 4 Decreased NADPH+H+ production (which is
essential to reduce glutathione in RBCs)
b) Reduced glutathione (G-SH) is needed to remove hydrogen peroxide (H202) which is toxic to the
cell.

SIGNS AND SYMPTOMS OF FAVISM

Hemolytic anemia in the form
of severe jaundice and
decreased hemoglobin.

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 CARBOHYDRATES METABOLISM 99

URONIC ACID PATHWAY

Definition It is a minor pathway, in which glucose is converted into glucuronic acid.
LOCATION OF THE PATHWAY:
- Intracellular location: Cytosol.
- Organ location: Mainly liver.
STEPS

FUNCTIONS (IMPORTANCE) OF URONIC ACID PATHWAY

This pathway produces glucuronic acid, which is important for:
A. Synthesis of substrates:
1. Glycosaminoglycans.
B. Conjugation reactions:
UPD-glucuronic acid is used for conjugation with many body compounds to make them more
soluble before excretion e.g. steroid hormones and bilirubin.
C. Detoxification reactions:
UDP-glucuronic acid is used for conjugation with toxic compounds to make them less toxic e.g.
phenols.

FATE OF GLUCURONIC ACID:

UDP-glucuronate is converted to glucuronate then → L-xylulose —> D-xylitol → D-xylulose →
which then joins pentose phosphate pathway to be completely oxidized.

DEFECTS OF URONIC ACID PATHWAY = ESSENTIAL PENTOSURIA:

1. Definition: It is benign rare hereditary disease
2. Cause: failure of conversion of L-xylulose into D-xylulose (due to deficiency of L-xylulose
reductase)
3. Manifestation: L-xylulose will accumulate and excreted in urine.
Give +ve Bendict test.

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100 CARBOHYDRATES METABOLISM

MCQ
30. All the dehydrogenases listed below are NAD+ dependent, EXCEPT:
a. Lactate dehydrogenase
b- Glucose-6-phosphate dehydrogenase
c- Pyruvate dehydrogenase
d- Glyceraldehyde-3-phosphate dehydrogenase

31. The following statements on glucuronic acid pathway are true EXCEPT:
a- It can be synthesized in the human body from active glucose.
b- It can be used in the synthesis of L- ascorbic acid in human body.
c- It is used in detoxication of benzoate.
d- It conjugates with bilirubin in the liver.
32. Which enzyme generates NADPH?
a- Pyruvate carboxylase
b- Pyruvate dehydrogenase
c- Glucose-6-phosphate dehydrogenase
d- Lactate dehydrogenase
33. Transketolase activity is decreased in the deficiency of:
a- Thiamine pyrophosphate (TPP)
b- Nicotinamide adenine dinucleotide
c- Flavin adenine dinucleotide
d- Pyridoxal phosphate
34. The HMP shunt pathway is important for all the following
a- Generation Of ATP
b- Fatty acid biosynthesis
c- Synthesis of reduced glutathione
d- Synthesis of ribose
35. HMP pathway occurs in the cytosol of:
a- Liver.
b- Adipose tissue.
c- Testis.
d- All of the above.
36. NADPH is important FOR ALL Except:
a- Fatty acid synthesis.
b-Hydroxylation reactions.
c- Gluconeogenesis.
d- Steroid synthesis.
37. Favism is due to deficiency of:
a- Glucose -6- phosphatase.
b- Pyruvate kinase.
c- G-6-P-dehydrogenase.
d- Aldolase B.

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 CARBOHYDRATES METABOLISM 101

Glycogen Metabolism
GLYCOGENESIS GLYCOGENOLYSIS
Def Formation of glycogen in liver and muscle. Breakdown of glycogen into glucose (in liver)
and lactate (in muscles)
Site Cytoplasm in liver and muscle Cytoplasm in liver and muscle
1. Activation of Glucose to (UDP- 1. Phosphorylase “Key enz.”.
Glucose): - Acts on α1-4 bonds, breaking it down by
phosphorolysis. - It
removes glucose units in the form of glucose-
1-phosphate.
- It acts on the branches containing more
than 4 glucosyl units.
2. Formation of glycogen primer which: 2. Transferase:
- Few molecules of glucose react with OH of - When the branch contains 4 glucose units,
tyrosine of a protein called glycogenin. 3 of them are transferred to a next branch by
3. Glycogen synthase “Key enz.” transferase enzyme leaving the last one.
- UDP-G molecules are added to glycogen 3.Debranching enzyme:
primer causing elongation of the α1-4 Removes the last glucose unit that is
Steps
branches up to 12-14 glucose units. attached to the original branch by α1-6 bond.
4. Branching enzyme:
-Transfers parts of the elongated chains (5-8
glucose residues) to the next chain forming a
new α1-6 glycosidic bond.

Liver Glycogen Muscle Glycogen

From bl. glucose, other Hexose & lactate From blood only
120 gm. = 6% 350gm. = 1%
Correct blood glucose ATP for muscle only
Contain G-6-phosphatase NO G-6-phosphatase
Stimulated by Glucagon NO effect

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102 CARBOHYDRATES METABOLISM

REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS

There is a coordinated regulation of glycogenesis and glycogenolysis i.e. conditions stimulate
glycogenolysis, inhibit glycogenesis at the same time and vise versa.

GLYCOGEN STORAGE DISEASES

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 CARBOHYDRATES METABOLISM 103

GLUCONEOGENESIS

DEFINITION
Gluconeogenesis is the formation of glucose from non-carbohydrate sources.
These sources include:
- Lactate. - Pyruvate. - Glycerol.
- Some amino acids. - Propionate (in ruminants only).
SITE
A. Intracellular location: Cytosol & mitochondria.
B. Organ location: 1. Liver (90%).
2. Kidney (10%).
STEPS
The steps of gluconeogenesis are mainly the reversal of glycolysis, except for the three irreversible
kinases which are replaced by the following enzymes:
Glycolysis Gluconeogenesis
Glucokinase. Glucose-6-phosphatase.
Phosphofructokinase -1. Fructose 1, 6 bisphosphatase.
Pyruvate kinase. Pyruvate carboxylase.
Phosphoenol pyruvate carboxykinase.
1. Pyruvate to phosphoenol pyruvate:
▪ This conversion is done by dicarboxylic acid shuttle and needs 2 enzymes:
a) Pyruvate carboxylase: present in mitochondria.
b) Phosphoenol pyruvate carboxykinase: present in Cytosol.
▪ Pyruvate should pass first from Cytosol to mitochondria by special transporter.
▪ Pyruvate is then converted into oxaloacetate by pyruvate carboxylase (in the presence of
biotin, CO2 and ATP).
▪ The mitochondrial membrane is impermeable to oxaloacetate. So, oxaloacetate is converted
to Malate by (Malate dehydrogenase).
▪ Malate is transported to Cytosol, where it is converted again into oxaloacetate (by Cytosolic
Malate dehydrogenase).
▪ Oxaloacetate is converted into phosphoenol pyruvate by (phosphoenol pyruvate
carboxykinase).
N.B. : Pyruvate never goes in the course of citric acid pathway to reach Malate,
Because this pathway needs insulin and other factors.
2. Fructose 1,6 bisphosphate to fructose-6-phosphate:
This reaction is catalyzed by the enzyme (fructose 1, 6 bisphosphatase).
3. Glucose-6-phosphate to glucose:
This reaction is catalyzed by the enzyme (glucose-6-phosphatase).

PATHWAYS FOR DIFFERENT SOURCES OF GLUCONEOGENESIS

A. gluconeogenesis from lactate:
B. Gluconeogenesis from glutamate:
Glutamate is converted into α-Ketoglutarate by transamination reaction → krebs
D. Gluconeogenesis from Glycerol:
C. Gluconeogenesis from Propionic acid:
- This occurs only in ruminants and not in human.
- Propionic acid is converted into Succinyl CoA → Malate → common pathway.

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 CARBOHYDRATES METABOLISM 105

REGULATION OF GLUCONEOGENESIS
gluconeogenesis& glycolysis are reciprocally regulated
A. Hormonal regulation:
Glucagon (+) Cortisol (+) Insulin (-)
-Secreted in response to hypoglycemia. - ↑ synthesis of gluconeogenesis - Secreted in response to
- ↑ synthesis of gluconeogenesis enz. enz. hyperglycemia.
- inhibit glycolysis. -↑ protein catabolism - inhibit of
- stimulate insulin secretion. -↑glycogenic amino acids gluconeogenesis enzymes
- inhibit glycolysis. - stimulate glycolysis.

B. Substrate regulation: Acetyl CoA and ATP

1. Stimulate gluconeogenesis by inhibiting glycolysis (through inhibiting PFK-1) and stimulate
gluconeogenesis (by stimulating fructose1, 6 bisphosphatase).
2. Acetyl CoA also stimulates pyruvate carboxylase (gluconeogenesis)
And inhibit pyruvate dehydrogenase (oxidation).

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106 CARBOHYDRATES METABOLISM

MCQ
38. Gluconeogenesis is inhibited by:
a- Glucagon b- Growth hormone c- Insulin d- Glucocorticoids
39. All the following are key gluconeogenic enzymes EXCEPT:
a- Pyruvate carboxylase b- Phosphoenol pyruvate carboxykinase
c- Phosphofructokinase d- Glucose-6-phosphatase
40. How many ATP molecules are required to convert 2 molecules of pyruvate into
glucose?
a- Two b- three c- Six d- Eight
41. All the following are substrates for gluconeogenesis Except
a- palmitic acid b- Lactic acid c- Alanine d- Glycerol
42. The hormone activating the enzyme glycogen phosphorylase is:
a- Epinephrine b- Insulin c- Growth hormone d- Glucocorticoids
43. Von Gierk's disease is characterized by the deficiency Of:
a- Glucose-6-phosphatase b- Glyceraldehyde-3-phosphate dehydrogenase
c- Phosphofructokinase d- Phosphorylase
44. As regards glycogen:
a- It is a highly branched polymer of aD glucose.
b. The glucose residues are united by a, and a, glucosidic bonds.
c- Glycogen stores in muscles are more than that of liver.
d- All of the above.
45. Glycogen phosphorylase is:
a- The key enzyme of glycogenesis. b- Activated by lcAMP.
c- Allosterically inhibited by ATP. d- Activated by insulin.
46. As regards Von Gierk's disease, all are correct, EXCEPT:
a- It is due to deficiency of G-6-phosohatase in the liver and kidneys.
b-There is fasting hypoglycemia.
c- There is hyperlipidemia and ketosis.
d- There is hypouricemia.
47. All gluconeogenic enzymes are present in cytosol, EXCEPT:
a- G-6-phosphatase.
b-Pyruvate carboxylase.
c- PEP carboxykinase.
d- Aldolase A.
48. One of the following cannot act as a precursor for gluconeogenesis
a- Lactate. b- Glycerol c- Alanine. d. Acetyl COA.

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 CARBOHYDRATES METABOLISM 107

GALACTOSE METABOLISM
IMPORTANCE OF GALACTOSE: IN THE FORM OF UDP-GALACTOSE
A. Synthesis of lactose (= Milk sugar).
B. Synthesis of glycolipids (cerebrosides).
C. Synthesis of glycoproteins and proteogIycans.
D. Synthesis of glycosaminoglycans.
CONVERSION OF GALACTOSE INTO GLUCOSE
A. Site: Liver.
B. Steps:

GALACTOSEMIA
Definition: It is increase blood galactose concentration due to inability to metabolize galactose.
Causes: Inherited enzyme deficiency of:
1. Galactokinase.
2. Galactose-1-P uridyl transferase:
3. Epimerase.
Effect: a) Infantile Cataract = opacity of eye lens:
Galactose in the eye is reduced by an enzyme called Aldose reductase
into galacticol, which accumulates causing cataract.
b) Liver failure.
c) Mental retardation.
d) Galactosuria: excretion of galactose in urine.
CONVERSION OF GLUCOSE INTO GALACTOSE IN MAMMARY GLAND AND LACTOSE SYNTHESIS
Lactose is a disaccharide formed of β -galactose attached to α-glucose
by β1-4 bonds. It is called milk sugar
Steps: 1. Glucose is first converted into UDP-galactose.
2. UPD-Galactose reacts with a molecule of glucose in the presence of
enzyme to form lactose.

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108 CARBOHYDRATES METABOLISM

FRUCTOSE METABOLISM

DIETARY SOURCES OF FRUCTOSE

- Sucrose: (table sugar): Hydrolysis of sucrose → glucose and Fructose
- In honey and in many fruits and vegetables as a monosaccharide.
IMPORTANCE OF FRUCTOSE
A. Energy production: 15% of daily energy is derived from fructose.
B. Fructose is the major energy source for spermatozoa in the seminal vesicle.
METABOLISM OF FRUCTOSE
A. In the liver:
1. Liver contains fructokinase enzyme, which phosphorylates fructose into fructose-1-
phosphate.
2. Fructose-1-phosphate by aldoase B enzyme → Dihydroxyacetone phosphate +
glyceraldehyde.
3. Glyceraldehyde → glyceraldehydes-3-phosphate.
4. Glyceraldehyde-3-p + Dihydroxyacetone may undergo:
a) Glucose formation (gluconeogenesis) main pathway.
b) Oxidation to pyruvate (glycolysis).
B. In extra-hepatic tissues:
1. Because fructokinase is not available in muscles and adipose tissue, fructose is metabolized
by Hexokinase and other enzymes into pyruvate → oxidation
C. In the testis (seminal vesicle, lens, peripheral nerves and renal glomeruli:
1. Glucose is converted into fructose through sorbitol formation:
2. Fructose is the main nutrient for sperms.
3. Deficiency of fructose in semen correlates with male infertility.
GENETIC DISORDERS OF FRUCTOSE METABOLISM
1- Essential fructosuria:
1. Cause: Due to deficiency of Fructokinase enzyme.
2. Effect: Not serious condition. The excess accumulated fructose is lost in urine.
2- Hereditary fructose intolerance.
1. Cause: Due to deficiency of Aldolase-B enzyme. This leads to accumulation of
Fructose-1-phosphate.
2. Effect: the accumulation of Fructose-1-phosphate leads to:
a) Damage of liver and kidney tissues → Liver and kidney failure.
b) Inhibition of Phosphorylase enzyme. This leads to inhibition of glycogenolysis
and fasting hypoglycemia.

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 CARBOHYDRATES METABOLISM 109

MCQ
49. All are true as regards fructose intolerance
a- Defective enzyme is aldolase-B
b- Fructose-I-phosphate accumulates
c- Glycogen phosphorylase is inhibited
d- Urine is free from fructose
50. Features of galactosemia include the following
a- Cataract
b- Hepatosplenomegaly
c- Mental retardation
d- Hemolytic anemia
51. The commonest deficient enzyme in Galactosemia is:
a- Galactokinase
b- Galactose -1- P uridyl transferase
c- UDP transferase
d- Galactose -l phosphatase.
52. Hereditary fructose intolerance is a condition caused by a deficiency of:
a- Phosphofructokinase.
b- Fructokinase.
c- Aldolase B.
d- Fructose 6-phosphatase.

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110 CARBOHYDRATES METABOLISM

BLOOD GLUCOSE

PLASMA GLUCOSE LEVELS

A. Fasting level = 65-110 mg/dl (3.6-6.1 mmol/L)
B. One hour after carbohydrate meal = 120-150 mg/dl (6.7-8.3 mmol/L).
C. Two hours after carbohydrate meal (PP) = 65-140 mg/dl (3.6-7.8 mmol/L).

REGULATION OF BLOOD GLUCOSE LEVEL

Hormonal regulation Organ regulation

Insulin Liver
the only hormone which reduces blood During fasting:
glucose level through: - Glycogenolysis.
Stimulation of: - Glucose uptake by cell. - Gluconeogenesis.
- Glucose oxidation. - Ketogenesis.
- Glycogenesis. After carbohydrate meal:
- Lipogenesis. 60% of glucose is taken up by liver, and
converted into glucose-6-phosphate, by
Inhibition of: - Glycogenolysis. Glucokinase enzyme:
- Gluconeogenesis. - Glucose-6-phosphate will undergo one of the
following fate in the liver:
- (Glycogenesis)
- (lipogenesis).
Glucagon Kidney
Stimulation of: - Glycogenolysis - Glucose is completely reabsorbed by kidney
- Gluconeogenesis. until reaching renal threshold (Average 180
Catecholamines mg/dl).
Stimulation of: - Glycogenolysis - Then appears in urine (glycosuria).
Low renal threshold:
Glucocorticoids - Normally in some persons due to defective
Stimulation of: - Gluconeogenesis. tubular enzymes for
- ↑ Ptn catabolism→↑a.a. Glucose reabsorption (diabetes innocence).
Growth hormone - In 20% of pregnant females.
Inhibition of: glucose uptake by cells. High renal Threshold:
Blocks: insulin action at cell membranes. - In Elderly people due to reduced glomerular
filtration rate.
- In cases of diabetes with renal damage.

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 CARBOHYDRATES METABOLISM 111
VARIATIONS IN BLOOD GLUCOSE
Hypoglycemia Hyperglycemia
Definition: Definition:
Decrease of blood glucose concentration below It is the rise of blood glucose above normal
normal fasting average concentration: less than 65 average level.
mg/dl.
Mechanism: Causes:
Hypoglycemia activates: 1. Diabetes mellitus: CC
1- α- Cells of islets of Langerhans → ↑Glucagon + 2. In patients receiving intravenous fluid
↑Glycogenolysis →↑Blood glucose. containing glucose.
2- Receptors in hypothalamus: This stimulates 3. Temporarily in severe stress.
Secretion of epinephrine (mediated by autonomic 4. After cerebro-vascular accidents.
nervous system). 5. Disturbance in hyperglycemic hormones.

Types and causes of hypoglycemia:

Types Organ or cause Examples
Fasting - Pancreas Insulinoma.
- Other endocrine Adrenocortical
gland hypofunction.
Liver Prolonged starvation.
Stimula -Drugs and Poisons ↑insulin or
tive ↑sulphonylurea.
- Liver poisons
-Postgastrectomy
- Leucine
- hypersensitivity
- Inborn errors of - Galactosemia
metabolism - fructosemia
- Von Gerkie’s D

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CHO DISEASE
DISEASE DEFICIENCY OF EFFECT
1- Osmotic pressure
1. Lactose
→ Dehydration &
intolerance
causing diarrhea.
LACTOSE Maybe: Lactase enzyme
2- ↑ fermentation of
1- congenital (Rare)
lactose by bacteria →
2- Acquired (Common
Abdominal cramps.
Pyruvate kinase ↓rate of Glycolysis
1- Hemolytic anemia → ↓production of
Hexokinase
ATP
GLYCOLYSIS
Causes of lactic acidosis:
2-Lactic acidosis a- Increase formation of lactate
b- Decrease utilization of lactate.
a- ↓NADPH+H→↓
1- Favism:
reduced
(Hemolytic anemia)
glutathone→
In the form of severe
accumulation of H2O2
jaundice & ↓HB
Glucose -6- →Hemolysis of RBCs.
HEXOSE conc.
phosphate b- H2O2 conversion
PHOSPHATE Precipitating factors:
dehydrogenase HB
PATHWAY a- Oxidant drugs e.g.
into Met-hemoglobin
OR (PPP) sulpha & Primaquine
→ the RBC
Anti-malarial,
membrane
b- Fava beans.
fragility.
2- Chronic bacterial
NADPH+H+ oxidase
infection
URONIC ACID L- xylulose
Essential pentosuria pentosuria
PATHWAY reductase
Von Gerkie’s disease Severe fasting hypoglycemia,
Glucose-6-phosphatase
↑ glycogen in liver, ↑ blood
(type I) (# gluconeogenesis)
lactate, hepatomegally, Guat
Pompe's disease Lysosomal α-1,4-
Cardiomegaly and systemic
glucosidase
(type II) findings leading to early death
GLYCOGEN (acid maltase)
Cori's disease Milder form of type I with
STORAGE Debranching enzyme
normal blood lactate levels
(type lll) ( α-1,6-glucosidase)
DISEASES Gluconeogenesis is intact.
↑ glycogen in muscle, but
McArdle's disease Skeletal muscle glycogen cannot break it down, leading to
Phosphorylase
(type V) painful muscle cramps,
myoglobinuria
muscle
with strenuous exercise
Essential Fruktokinase fructosuria
FRUCTOSE - Liver and kidney failure
Fructose intolerance Aldolase-B
- fasting hypoglycemia

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114 LIPIDS METABOLISM

CHAPTER MAP

Lipids Metabolism
Feeding state Fasting state
‫واحنا واكلي‬ ‫واحنا صايمي‬
‫هيكون يف انسولي‬

1- Fatty acid synthesis 1- Lipolysis

2- Lipogenesis 2- Fatty acid oxidation
3- Cholesterol synthesis 3- Ketogenesis
4- Conjugated lipid 4- Ketolysis
synthesis

FATE OF ABSORBED LIPIDS

A. After fatty meal plasma shows a milky appearance. This due to venous blood contains excess
chylomicrons after absorption.
- Excess chylomicrons stimulate mast cells to produce heparin. Heparin then stimulates the lining
epithelium of blood vessels of heart, lungs, spleen and adipose tissue to produce an enzyme
called: lipoprotein lipase (plasma clearing factor).
- Lipoprotein lipase enzyme will act on triacylglycerols of chylomicrons, converting them into
glycerol and free fatty acids.
B. Glycerol and fatty acids are taken up by different tissues for the following fate:
1. Formation of depot fat (adipose tissue).
a) It is formed mainly of Triacylglycerols b) It is present in fat cells of adipose tissue.
2. Oxidation for production of energy:
a) Fatty acids: Converted into acetyl CoA that is oxidized in citric acid cycle.
b) Glycerol: Converted into glycerol-3-phosphate (by glycerol kinase). This is then converted
into DHAP. The later will undergo oxidation in glycolysis.
3. Glucose formation by gluconeogenesis:
a) Glycerol → Glucose.
b) Odd number fatty acids oxidation → Propionyl CoA → Glucose.
4. Synthesis of biologically active compounds: e.g. different steroids and eicosanoids
5. Synthesis of tissue fats (structural cellular fats).

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STORAGE AND MOBILIZATION

- Body lipids are of 4 types: tissue lipids, adipose tissue (depot fat), plasma
lipoproteins and bone marrow lipids.
Tissue lipids Adipose tissue (depot fat)
- These lipids Brown adipose tissue
White adipose tissue
enter in the
structure of body a) Composition: a) Certain areas of adipose
cells as cell 1) Triacyiglycerols: main content that contain tissue appear brown as they
membrane and saturated and unsaturated fatty acids. This contain high content of
mitochondria. makes depot fat in a fluid state at body mitochondria, cytochromes
- Tissue lipids temperature. and well developed blood
never oxidized to 2) Little phospholipids and cholesterol. supply.
give energy. b) Site: b) Function:
1) Under skin and in the breast. Production of heat. They
2) Around important organs e.g. kidney. contain a protein called
3) In the omentum and mosentry. Thermogenin. This protein acts
c) Sources: as Uncoupler of oxidative
1) Absorbed fat. 2) Carbohydrate. phosphorylation → ↓ATP
d) Functions: depot fat is important for: production and ↑heat
1) Energy production: During fasting, the generation.
triacylglycerols stored in depot fat provide the c) Site: common in animals
body with free fatty acids that oxidize to give exposed to cold atmosphere
energy. for warmness: It is little in
2) Fixation of some organs e.g. kidney. human, especially in obese
Heat insulator around the body. persons.
4) Production of vitamin D3: by exposure of skin
to ultraviolet rays

LIPOLYSIS
DEFINITION hydrolysis of Triacylglycerols in adipose tissue into glycerol and fatty acids.
STEPS
Lipolysis is carried out by a number of lipase enzymes, which are present in adipose tissue. These are
1. Hormone sensitive triacylglycerol lipase.
2. Diacylglycerol lipase.
3. Monoacylglycerol lipase.
FATE OF PRODUCTS OF LIPOLYSIS
1. Fate of fatty acids
a) Oxidation by tissue to give energy.
b) Fatty acids may remain in adipose tissue to be re-esterified into TAG again.
2. Fate of glycerol: Glycerol may diffuse to blood and then taken up by the liver to give:
1) Glucose by gluconeogenesis. 2) Pyruvate by glycolysis.
3) Triacylglycerols by lipogenesis.

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Regulation of Lipolysis
The key enzyme controlling Lipolysis is the
Hormone sensitive triacylglycerol lipase. It exists in 2 forms: active (Phosphorylated) and inactive
(dephosphorylated)
Causes of excessive Lipolysis: In conditions where the need for energy is increased
(low insulin and high glucagon):
1. Starvation.
2. Diabetes mellitus.
3. Low carbohydrate diet.
4. In certain infectious diseases as in tuberculosis (due to high catabolic state)

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 LIPIDS METABOLISM 117

Fatty acids oxidation

- 3 Different pathways for fatty acid oxidation are present: α, β and ω

β-OXIDATION
Site
1. Intracellular location: Mitochondria
2. Organ location:
a) Liver, kidney, heart and skeletal muscles.
b) β-Oxidation never occur in brain (can’t pass BBB) and RBCs (no mitochondria).
Mechanism
1- Activation of Fatty Acids.
Fatty acyl-CoA
COASH Synthetase
(Thiokinase) O
CH3 (CH2)n COOH CH3 (CH2)n C SCoA

Fatty Acid ATP AMP + PPi Fatty Acyl-CoA

Activation Of A Fatty Acid.

2- Transport of Acyl-CoA from Cytosol into Mitochondria by Carnitine Shuttle:
a) Structure of Carnitine:
Carnitine is β-hydroxy-γ-trimethyl ammonium butyric acid. It is derived from lysine amino
acid.
b) Function of Carnitine:
It transports long chain acyl CoA inside the mitochondrial matrix where enzymes for β-
oxidation are present.
c) Steps of shuttle three enzymes are involved
1. Carnitine acyl transferase I (Carnitine
palmitoyl transferase I)
- It is present in the outer mitochondrial
membrane.
- It transfers the acyl group from acyl CoA to
Carnitine to form acyl Carnitine.
2. Carnitine acylcarnitine translocase:
- It is present in the inner mitochondrial
membrane.
- It transports acyl Carnitine across inner
mitochondrial membrane (in exchange with
Carnitine).
3. Carnitine acylcarnitine transferase II (Carnitine
palmitoyl transferase II).
- It is present in the inner mitochondrial
membrane.
- It transfers the acyl group from acyl Carnitine to
form acyl CoA again.
3. Unsaturation of fatty acids: Catalyzed by fatty acyl CoA dehydrogenase enzyme.
4. Hydration: Catalyzed by enoyl CoA hydratase enzyme.
5. Oxidation: Catalyzed by β-hydroxy acyl CoA dehydrogenase enzyme.
6. Splitting (Cleavage) step: Catalyzed by Acyl CoA acyl transferase (thiolase) enzyme.

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‫‪118‬‬ ‫‪LIPIDS METABOLISM‬‬

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 LIPIDS METABOLISM 119
ENERGY PRODUCTION OF β -OXIDATION
- Calculation formula of energy production of oxidation of any fatty acids:
- Oxidation of one molecule of acetyl CoA in citric acid cycle gives 12 ATP.
- In each turn: 1 FADH2 → 2ATP 1 NADH+H → 3 ATP = 5 ATP
= {(N/2 - 1) x 5 ATP} + {N/2 x 12 ATP} - 2 ATP
-Two high energy phosphate bonds are utilized in the first reaction. Catalyzed by (acyl CoA
synthetase) which occurs for one time only.
e.g. palmitic acid (16 carbons):
= {(16/2 - 1) x 5 ATP} + {16/2 x 12 ATP} - 2 ATP
= {(35 ATP} + {96ATP} - 2 ATP = 129 ATP
IMPORTANCE (FUNCTIONS) OF β -OXIDATION:
1. Energy production e.g. palmitic acid produces 129 ATP.
2. Production of acetyl CoA: which enter in many pathways.
3. Ketone bodies formation: Acetoacetyl CoA is the last 4 carbons product in the course of β-
oxidation of even numbered fatty acids. It may be converted
into acetoacetate; one of ketone bodies (see later).
OXIDATION OF ODD NUMBER FATTY ACIDS:
1. They are oxidized by α-oxidation till a Propionyl CoA, (3 carbons) is produced. Then Propionyl
CoA is converted to Succinyl CoA
UNSATURATED FATTY ACIDS
- Their oxidation requires new enzymes in addition to the four enzymes.
- The pathways differ depending on the position in which the double bond is located.
a. For fatty acids that contain a double bond at an odd carbon number (e.g., between carbons
9 and 10), b-oxidation occurs until the double bond of the unsaturated fatty acid reaches
position 3 of the acyl CoA. At this point, an isomerase will convert the cisD3 double bond to a
transD2double bond. The normal steps of b-oxidation can then proceed.
b. For fatty acids that contain a double bond at an even carbon position (e.g., between
carbons 12 and 13), b-oxidation occurs until the double bond of the unsaturated acid reaches
position 4 of the acyl CoA.
After the acyl CoA dehydrogenase creates the trans double bond between carbons 2 and 3,
the enzyme 2,4-dienoyl CoA reductase reduces the two double bonds into one, generating a
trans D3 double bond. The trans D3 double bond is then isomerized to transD2,so that the
normal steps of b-oxidation can then proceed.

α-OXIDATION
- This type of oxidation occurs in α- position and characterized by:
1. It is a mechanism mainly for oxidation of branched chain fatty acid, which are methylated at β
position.
2. It is specific for oxidation of Phytanic acid (3, 7, 11, 15 tetramethyl palmitic acid), present in
plant foodstuffs.
3. It is minor pathway for fatty acid oxidation, occurs mainly in brain and nervous tissues.
- In α-oxidation, there is one carbon atom removed at a time from α position
- It does not require CoASH and does not generate high energy phosphate.
REFSUM’S DISEASE:
- Def: inherited deficiency of enzymes responsible for α-oxidation of Phytanic acid.
- Manifestation: accumulation of Phytanic acid in nervous tissue and produce nervous damage
e.g. deafness and blindness.

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120 LIPIDS METABOLISM

ω-OXIDATION
- It is oxidation of terminal CH3 group (ω carbon) of fatty acid.
- This produces dicarboxylic fatty acids. By β-oxidation they are converted to
adipic acid (6 carbons) and suberic acid (8 carbons).
- ω-Oxidation is a minor pathway for fatty acid oxidation and catalyzed by hydroxylase enzymes of
cytochrome P450

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KETONE BODIES
Definition
these are 3 compounds formed by the liver and include:

FUNCTIONS OF KETONE BODIES

- Source of energy: They are converted into acetyl-CoA which is oxidized in tricarboxylic acid
(TCA) cycle.
- Skeletal muscles, cardiac muscles, kidneys and most of tissues can use ketone bodies as a
source of energy in prolonged fasting and starvation.
- Brain tissue can also oxidize ketone bodies within 5 to 6 days of starvation.
Note: brain never oxidizes fatty acids.
- Liver does not contain enzymes for ketone bodies oxidation (ketolysis). Thus liver
cannot oxidize them.
Ketogenesis Ketolysis
location Organ Liver (partial oxidation) Extra-hepatic tissues

Intracellular Mitochondria

Precursor Acetyl CoA from: (F.A oxidation & Ketogenic a.a)

Steps 1. Formation of acetoacetyl CoA: - Acetone is volatile and removed in

a) From condensation of 2 acetyl CoA. the expired air.
b) Acetoacetyl CoA may also be derived from β- - β-Hydroxybutyrate is converted into
oxidation of F.A acetoacetate by hydroxybutyrate
2. Formation of HMG-CoA By condensation of dehydrogenase
third molecule of acetyl CoA in the presence of - Acetoacetate is then activated into
HMG CoA synthase Acetoacetyl CoA by:
3. Formation of acetoacetate by a) Thiophorase in the presence of
HMG CoA lyase. Succinyl CoA.
4. Acetoacetate is either: b) Acetoacetate synthetase in the
a) Spontaneously decarboxylated into acetone presence of ATP.
b) Reduced by hydroxybutyrate dehydrogenase - Acetoacetyl CoA is split into two
into β-hydroxybutyrate. molecules of acetyl CoA which are
oxidized in TCA

Regulation 1. After meal: insulin is secreted, and this inhibits Lipolysis and in turn inhibit Ketogenesis.
2. During fasting: glucagon. This stimulates Lipolysis and in turn Ketogenesis.

Conditions that increase Ketogenesis:

1. Fasting and starvation. 2. Carbohydrate poor diet. 3. High fat diet. 4. Diabetes mellitus
5. ↑ muscular exercise. 6. pregnancy

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BLOOD KETONE BODIES AND KETOSIS

- Blood ketone bodies concentration is less than 3 mg/dl.
- Ketonemia: is the increase of blood ketone bodies above normal concentration.
1. It occurs when the rate of Ketogenesis is greater than the rate of ketolysis.
- Urine ketone bodies: is less than 40 mg/day.
- Ketonuria: is the increase of urine ketone bodies above normal concentration.
1. It usually occurs with Ketonemia. 2. Concentration may reach 5000 mg/day.
CAUSES OF KETONEMIA AND KETONURIA
1. Starvation. 2. Severe diabetes mellitus. 3. Hypercatabolic states e.g. diarrhea
KETOSIS = (KETOACIDOSIS)
- Definition: It is a condition of metabolic acidosis results from Ketonemia.
- Mechanism: a) An increase of ketone bodies in the blood is neutralized by blood buffers mainly
bicarbonate (HCO3).
b) Bicarbonate will be depleted and this leads to decreased blood pH (acidosis).
- Effects of acidosis:
a) Acidosis causes dizziness, loss of concentration...etc.
b) Acidosis causes transfer of potassium (K+) ions from intracellular fluid to blood leading to (↑
K+) hyperkalemia.
- Ketotic coma: In severe cases of ketosis as in uncontrolled diabetes mellitus, coma may be
developed and the condition may be fatal.
Lipogenesis

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 LIPIDS METABOLISM 123

FATTY ACID SYNTHESIS

- There are 2 mechanisms for fatty acids synthesis: cytoplasmic and microsomal.
❖ CYTOPLASMIC SYSTEM (extra-mitochondrial) or (de novo)
- The main product of this pathway is palmitate (16C).
SITE
1. Intracellular location: Cytosol.
2. Organ location: Many tissues including liver, adipose tissue, lung and kidney.
REQUIREMENTS
❖ This pathway needs the following substrates: acetyl CoA, NADPH+H and group of enzymes called
fatty acid synthase complex.
1. Acetyl CoA:
- It is provided mainly by glucose through pyruvate (glycolysis).
- Acetyl CoA is formed in mitochondria and fatty acid synthesis occurs in cytosol.
- The acetyl CoA cannot diffuse to cytosol because mitochondrial membrane is impermeable to it.

2. NADPH+H: It is provided by 3 sources:

a) Pentose phosphate pathway.
b) Action of cytoplasmic (Isocitrate dehydrogenase) on Isocitrate. It is
+
similar to mitochondrial one but it uses NADP as hydrogen carrier.
c) Action of malic enzyme on malate to produce pyruvate.
3. Fatty acid synthase complex:
a) This enzyme is a dimer i.e. formed of 2 subunits.
b) Each unit, which is called monomer, contains 7 enzymes and a terminal protein called acyl
carrier protein (ACP).
c) Each monomer contains 2 -SH groups, one provided by phosphopantotheine and attached to
ACP. The other is provided by cysteine and attached to the enzyme 3-ketoacyl
synthase.
d) The 2 monomers are arranged head to tail, so the -SH group of ACP of one monomer is very
close to the - SH group provided by 3-ketoacyl synthase of the other monomer.
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REGULATION OF FATTY ACID SYNTHESIS

The key enzyme of cytoplasmic pathway is acetyl CoA carboxylase enzyme.

1- Insulin: Stimulates fatty acid synthesis

through:
a) Insulin activates both acetyl CoA
carboxylase and pyruvate dehydrogenase
[PDH]
b) Insulin stimulates also the transport of
glucose into cells.
c) Insulin inhibits Lipolysis.
2- Glucagon and epinephrine: Inhibits fatty
acid synthesis through cyclic AMP
- and it also stimulates Lipolysis
3- Long chain acyl CoA: Inhibits Fatty acid
synthesis through:
a) It inhibits allosterically acetyl CoA
carboxylase.
b) It inhibits transport of citrate from
mitochondria to cytosol.
c) It inhibits pyruvate dehydrogenase (PDH).
4- Citrate: stimulates fatty acid synthesis
through stimulation of acetyl CoA
carboxylase.

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STEPS OF CYTOPLASMIC PATHWAY
- Carboxylation of acetyl CoA to form malonyl CoA: (committed step in the pathway).
a) Malonyl CoA is synthesized from acetyl CoA by acetyl CoA carboxylase in the presence of
biotin and ATP.

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F.A synthesis F.A oxidation

Organ location Mainly liver Mainly liver and muscles

Intracellular location Cytosol Mitochondria

Nutritional state After meals Fasting

Hormonal stimulation Insulin Glucagon

Carrier of acetyl acyl group Carnitin (cytosol to

Citrate (mitochondria to
between cytosol and mitochondria)
cytosol).
mitochondria
> Acyl carrier protein > CoASH
Active carriers
> CoASH
Coenzyme NADP+ NAD+

Two carbon donor Malonyl CoA Acetyl CoA

Activator Citrate

Fatty acyl CoA (inhibits acetyl Malonyl CoA (inhibits Carnitine

Inhibitor acyl transferase)
CoA carboxylase)

Product of pathway Palmitate Acetyl CoA

MICROSOMAL PATHWAY FOR F.A. SYNTHESIS

- This is probably the main site for the elongation of

existing long chain fatty acid molecules i.e.
production of fatty acids longer than 16 carbon
atoms.
A. The elongated molecules (C10-C16) are derived
from:
1. Palmitate: by cytoplasmic pathway.
2. Fatty acids of diet.
B. The microsomal pathway needs malonyl CoA as
acetyl donor and NADPH+H+ as coenzyme.
C. Function: This system becomes active during
myelination of nerves in order to provide C22 and
C24 fatty acids which are present in sphingolipids.

SYNTHESIS OF UNSATURATED F.A

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Lipogenesis
DEFINITION
synthesis of triacylglycerols from fatty acids (acyl CoA) and glycerol (glycerol-3-phosphate).
STEPS
1. Activation of fatty acids into fatty acyl CoA

2. Synthesis of glycerol phosphate

a) In liver, kidney, intestine, and
lactating mammary glands:
Glycerol phosphate is formed
from
Glycerol by glycerokinase or from
glucose through glycolysis.
b) In muscles and adipose tissue:
glycerokinase is deficient. In these
tissues glycerol phosphate is
formed from glucose (through
glycolysis).
3. Synthesis of triacylglycerol: by
reaction between acyl CoA and
glycerol phosphate.
REGULATION OF LIPOGENESIS
1. After meal, lipogenesis is
stimulated: Insulin is secreted
which stimulates glycolysis.
Glycolysis supplies
dihydroxyacetone phosphate that
converted into glycerol phosphate
in adipose tissue.
2. During fasting lipogenesis inhibited:
as anti-insulin hormones e.g.
glucagon is secreted. These inhibit
lipogenesis and stimulate Lipolysis.

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128 LIPIDS METABOLISM

METABOLISM OF CHOLESTEROL

STRUCTURE
- Cholesterol is an animal sterol.
- It is a solid alcohol having group at C3
SOURCES OF CHOLESTEROL
A. Endogenous: Cholesterol is formed
in the body almost in all nucleated
cells from Acetyl-COA (about 700
mg/day).
B. Exogenous: Cholesterol occurs only
in food of animal origin such as egg
yolk, meat, liver and brain. Diet
supplies about 400 mg/day.

SYNTHESIS OF CHOLESTEROL
A. Location:
1. Intracellular location: Cytosol.
2. Organ location: a) Liver is the major
b) Other tissues e.g. intestine, adrenal cortex, gonads and skin.

B. Precursor: Acetyl CoA.

C. Steps:
1. Formation of acetoacetyl CoA: by
condensation of two molecules
acetyl CoA:
2. Conversion of acetoacetyl CoA to
mevalonate
3. Conversion of mevalonate to
cholesterol.

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REGULATION OF CHOLESTEROL SYNTHESIS
HMG COA reductase the key enzymes for cholesterol synthesis. It is present in two
forms: active dephosphorylated and inactive Phosphorylated. It is Regulated
through:
1. Feedback inhibition: Cholesterol acts as feedback inhibitor of HMG COA
reductase enzyme. Thus, it decreases more cholesterol synthesis.
2. Feedback regulation: Cholesterol (either synthesized by the cell or reaching it
from diet) inhibits HMG COA reductase gene. this decreases transcription and
synthesis of HMG CoA reductase.
3. Hormonal regulation:
a) Glucagon: Inhibits HMG CoA reductase.
b) Insulin: Stimulates HMG CoA reductase.
4. Inhibition by drugs:
Lovastatin and mevastatin are drugs, which inhibit HMG CoA reductase by
reversible competitive inhibition. They are used to decrease plasma cholesterol
levels in patients with hypercholesterolemia.

FUNCTIONS OF CHOLESTEROL
it is important for:
1. It enters in the structure of everybody cell particularly:
a) Cell membranes.
b) In nervous tissue.
2. Synthesis of steroid hormones.
3. Synthesis of bile salts.
4. Synthesis of vitamin D3.
EXCRETION
- One gram daily → - ½ as such with bile. - ½ converted to bile.
- Some cholesterol is synthesized by intestinal cells and modified by bacteria
before excretion. Bacterial enzymes reduce cholesterol into coprostanol,
excreted in feces

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PLASMA CHOLESTEROL
A. Cholesterol present in plasma is either free or esterified (cholesteryl ester).
1. Total plasma cholesterol: 140 —220 mg/dl.
2. Free plasma cholesterol: 26 — 126 mg/dl.

Hypercholesterolemia Hypocholesterolemia
Definition: It is increased plasma cholesterol Definition: It is decreased plasma
concentration above 220 mg/dl. cholesterol concentration below 140 mg/dl

- Diet rich in carbohydrate, cholesterol - Fasting → ↓ insulin

- diabetes mellitus - Unsaturated fatty acid diet
- Obesity - Liver diseases.
- Hyperthyroidism
- Kidney affection (nephrotic syndrome)
- Chronic infection
- Hypothyroidism as thyroxin stimulates
conversion of cholesterol to bile acids.
- Obstructive jaundice
- familial Hypercholesterolemia

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 ‫‪LIPIDS METABOLISM‬‬ ‫‪131‬‬

‫‪EICOSANOIDS‬‬

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METABOLISM OF CONJUGATED LIPIDS

SYNTHESIS OF GLYCEROL PHOSPHOLIPIDS

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SYNTHESIS OF SPHINGOPHOSPHOLIPIDS

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Degradation of phospholipids
- Phosphoglycerides are degraded by Phospholipases A1, A2, C and D.

- Sphingomyelin is degraded by lysosomal enzymes, sphingomyelinase its

deficiency leads to a disease called Niemann Pick disease.
- It is characterized by enlarged liver and spleen and death at early life
- Plasma enzyme called LCAT (lecithin cholesterol acyl transferase) can act upon
second fatty acyl CoA of converting it into lysolecithin.
Lecithin + Cholesterol LCAT Cholesterol ester + lysolecithin
FUNCTIONS OF PHOSPHOLIPIDS
- Phospholipids enter in the structure of cell membrane.
- Phospholipids containing Choline (e.g. lecithin) act as neurotransmitters. They
also act as methyl donors in transmethylation reaction.
- Phospholipids act as lipotropic factors i.e. prevent accumulation of fat in liver
and hence prevent fatty liver.
- Dipalmityl lecithin acts as surfactant in the lungs. It prevents adherence of
alveolar wall. Its deficiency leads to respiratory distress syndrome in premature
babies
- Cephalin has a role in coagulation mechanism.
- Lipositol (Phosphatidyl Inositol) acts as precursor for Inositol triphosphate.
That acts as 2nd messenger, mediating action of some hormones inside target
cells.
- Phospholipids in bile make cholesterol soluble. Their deficiency leads to
cholesterol gallstones.
METABOLISM OF GLYCOLIPIDS (SPHINGOLIPIDS):
- Glycolipids are lipid containing carbohydrates
- They also contain sphingosine and one fatty acid. They differ from each other
according to the type of carbohydrate content.
SYNTHESIS OF CEREBROSIDES
They Contain galactose.
1. Synthesis of sphingosine 2. Formation of ceramide. 3. Activation of galactose

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DEGRADATION OF CEREBROSIDES
is by glucocerebrosidase its deficiency leads to a disease called Gaucher’s disease.
- It is characterized by mental retardation and enlarged liver and spleen in
children,
LIPIDOSIS:
- Errors of phospholipids and sphingolipids metabolism:
- These are a group of diseases in which there is abnormal accumulation of
Phospholipids and glycolipids in nervous tissue. They are common in children.
They are characterized by:
1. Deficiency of specific lysosomal enzymes responsible for degradation of
sphingolipids
2. Accumulation of sphingolipids in tissues leads to their enlargement e.g. liver
and spleen enlargement
3. Mental retardation is present in many diseases
4. The most common diseases are Gaucher’s disease and Niemann Pick diseases.

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LIPOPROTEINS
CHYLOMICRONS METABOLISM
1-Site of synthesis: intestinal mucosal cells
2-Functions: transport dietary lipids from intestine to peripheral tissues.
3-Structure:
a- Main lipids: triacylglycerols. Chylomicrons contain also cholesterol,
phospholipids and fat soluble vitamins.
b- Proteins: (2%), apo B48 and receives apo CII and apo E from HDL.
4-catabolism: TG are hydrolyzed by lipoprotein lipase (which is activated by apo
CII). The remaining parts are chylomicron remnants, which are then taken up by
the liver. Hepatocyte receptors can recognize apo B48 and apo E.

VLDL METABOLISM
1- Site of synthesis: Liver.
2- Functions: transport lipids mainly TG from liver to peripheral tissues.
3- Structure:
a- Main lipids: triacylglycerols. It contains also cholesterol, phospholipids.
b- Proteins: (12%), apo B100 and receives apo CII and apo E from HDL.
5- Catabolism: TG are hydrolyzed by lipoprotein lipase (that is activated by apo
CII). The remaining parts are IDL, which are then converted into LDL by
transferring phospholipids, apo CII and apo E to HDL.
LDL METABOLISM
1-SITE OF SYNTHESIS: circulation from VLDL.
2-FUNCTION: LDL particles provide cholesterol to peripheral tissues.
3-STRUCTURE:
a- Lipid contents: cholesterol, cholesterol esters and phospholipids.
b- Protein contents: (22%), apo B100
4-CATABOLISM:

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LDL apo B100 are recognized by tissue receptors. After binding with receptors, the
LDL are internalized by endocytosis. Inside cells LDL are separated from receptors
and hydrolyzed by lysosomal enzymes releasing cholesterol, amino acids, fatty
acids and phospholipids.
*If the cell contains oversupply of cholesterol from LDL, HDL or chylomicron
remnants, the cholesterol amount can be decreased by:
a- Inhibition of HMG-CoA reductase → Inhibition of cholesterol synthesis.
b- Stimulation of ACAT enzyme → Cholesterol ester.
c- Inhibition of synthesis of LDL receptors → inhibition of LDL uptake by cells

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HDL METABOLISM
1-Site of HDL synthesis: Liver.
2-Functions:
a- Contain Apo CIl, which activates lipoprotein lipase that hydrolyzes TG.
b- Remove cholesterol from peripheral tissues and esterified it by LCAT enzyme
→ Cholesterol esters.
c- Carry cholesterol esters to VLDL & chylomicrons to the liver.
3-Structure:
a- Main lipids: cholesterol (free and esterified) and phospholipids, mainly lecithin.
b- Proteins: (50%), apo A-1 (which activates LCAT), apo CII (which activates
lipoprotein lipase and E (which is recognized by hepatic receptors)
4-Catabolism: HDL accepts unesterified cholesterol from peripheral tissues. Then
HDL particles (by LCAT enzyme) esterify cholesterol into cholesterol esters. Then
HDL is taken up by the liver cells where Cholesterol esters are released inside them
to be utilized in the formation of lipoproteins or excreted in bile.

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APOPROTEINS (APOLIPOPROTEINS)
- Definition: These are proteins (globulins) present in association with plasma lipids
to form lipoproteins.
- Functions:
1. Apolipoproteins form with lipids water-soluble compounds, so they help
transport of lipids between tissues.
2. Some apoproteins activate certain enzymes e.g. Apo C II activates lipoprotein
lipase and Apo-A1 activates LCAT.
3. They act as liganda (connection) for interaction of lipoprotein with their
receptors in tissues i.e. receptors of lipoproteins in tissues can recognize
lipoproteins through their apoproteins e.g. apo B100 for LDL receptors
CIassification
APOLIPOPROTEINS LIPOPROTEIIIS COMMEIIT
Apo A-I HD L *Activator of LCAT
*Legend for HDL-receptors
Ape B- 100 LDL-YLDL-IDL *synthesized by liver
*Legend for LDL-receptcrs
Ape B- 48 Chylomicrons - *Synthesized by intestine
chylomicron remnants *Legend for chylomicron remnant
receptors in Liver.
Ape C II Chylomicrons-VLDL-HDL Activator of lipoprotein lipase
Ape D HDL May act as lipid transfer protein.
Ape E Chylomicrons - * Legend for chylomicron remnant
Chylomicron remnants – receptors in liver.
VLDL - HDL * Legend for LDL receptors in tissues.

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 PROTEINS METABOLISM 141

CHAPTER MAP

ptn Metabolism
Amino Acid
CATABOLIC PATHWAYS Ammonia And Urea
Metabolism
1- Transamination. 1- Source and fate of 1- Glycine
2- Deamination ammonia. 2- Phenyl alanine
3- Transdeamination 2- Ammonia intoxication 3- Tyrosine
4- Decarboxylation. 3- Urea cycle 4- Tryptophan

5- Rest of A.A

GENERAL CATABOLIC PATHWAYS OF AMINO ACIDS

In human, the end products of protein and amino acids catabolism are ammonia and
urea. They are produced through the following catabolic pathways.
➢ Transamination.
➢ Deamination: Oxidative - Non oxidative - Hydrolytic.
➢ Transdeamination: i.e. transamination followed by deamination.
➢ Decarboxylation.

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DEAMINATION
DEFINITION
It is the removal of amino group from amino acids in the form of ammonia (NH3).
SITE
Mostly liver and kidney.
TYPES
1- Oxidative, 2-NON-Oxidative, 3-hydrolytic deamination.
1- Oxidative

L-glutamate
L. a.a oxidase D.a.a oxidase
dehydrogenase
Carrier FMN FAD NAD or NADP.

Site Liver & kidney Liver & kidney Most tissues.

Activity Low highly active highly active

Reversibility Irreversible irreversible Reversible

2- Non-oxidative deamination
- For hydroxy amino acids e.g. serine, threonine, without removal of (H+)
- Its coenzyme is: pyridoxal phosphate (PLP).

3- Hydrolytic deamination
For glutamine and asparagine For adenosine monophosphate (AMP):
- Enz → glutaminase & asparaginase - In muscles, AMP is hydrolytically deaminated
- Glutaminase is present in kidney. into inosine monophosphate
- It produces ammonia (NH3), which is used in Producing (NH3). This occurs by a series of
regulation of acid base balance reactions called: (IMP – AMP) cycle.

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TRANSAMINATION
DEFINITION
- It is the transfer of amino group from α-amino acid to α-ketoacid to form a new α-amino acid
and a new α-ketoacid.
MECHANISM
1. By enzymes called transaminases (or amino transferases) catalyze transamination.
2. Pyridoxal phosphate (PLP = active vitamin B6) is the coenzyme of all transaminases.
3. For all amino acids except: (lysine, threonine, proline and hydroxyproline).
4. All transamination reactions are reversible.
5. Present either in cytosol or in both cytosol and mitochondria of most tissues.
6. Among all transaminases, 3 are present in most mammalian tissues and they are of clinical
importance. These are: ALT, AST and glutamate transaminase.
Enzymes Site Function
Alanine transaminase (ALT): cytosol ALT is an enzyme that catalysis the
or transfer of amino group from Alanine
Glutamate pyruvate transaminase (GPT). to α-Ketoglutarate to form glutamate
and pyruvate.
Alanine + α-Ketoglutarate ALT PLP pyruvate + glutamate

Aspartate transaminase (AST): cytosol and catalysis the transfer of amino group
or mitochondria from Aspartate to α-Ketoglutarate to
Glutamate oxaloacetate transaminase form Glutamate and oxaloacetate.
(GOT).
Aspartate + α-Ketoglutarate AST PLP oxaloacetate + glutamate
Glutamate transaminase: Catalysis the transfer of amino group
from any amino acid to α-
Ketoglutarate.
Role of pyridoxal phosphate in transamination
Acts as an intermediate carrier of amino group.
Functions of transamination
1. Transfer of amino group (-NH2) from most amino acids to α-Ketoglutarate to form glutamate
then deaminated to give ammonia.
2. Transamination is important for formation of non-essential amino acids.
Diagnostic importance of transaminases (ALT and AST): normally intracellular
↑ ALT → liver diseases
↑ AST → heart muscle (myocardial infarction), skeletal muscle or kidney.
↑ Both → damage of liver cells with escape of hepatic enzymes into blood.

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TRANSDEAMINATION
Definition:
- It is transamination of most amino acids with α-Ketoglutarate to form glutamate, Then glutamate
is deaminated to give ammonia (NH3).
- It is the main pathway by which amino group (NH2) of most amino acids is released in the form of
ammonia (NH3).

DECARBOXYLATION
Definition:
removal of CO2 of amino acids produces the corresponding amines.
Functions:
• Some amines have important biologic functions: e.g.
1. Histamine (from histidine) is vasodilator.
2. γ-Amino butyric acid (from glutamate) is neurotransmitter.
Destruction of amines
- The resulting amines are further oxidized -after carrying out their functions by amine oxidase
enzymes.
- Amine oxidase enzymes are two types: monoamine oxidase and diamine oxidase. Both contain
Pyridoxal phosphate and copper as prosthetic groups.
e.g. ??

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AMMONIA (NH3)
DEFINITION
- Ammonia is a toxic substance especially to the central nervous system.
- Any ammonia formed in the peripheral tissue must be moved to the liver to be converted into
urea.
- This maintains ammonia at low level in circulating blood.
BLOOD AMMONIA
- Blood contains traces of ammonia: 10- 80 ug/dI.

Sources and fate of ammonia

SOURCES FATE
1. Transdeamination of amino acids: 1. Formation of non-essential amino acids: Through
In Many tissues, particularly liver Transdeamination.
2- Glutamine: The kidneys form ammonia 2. Formation of glutamine:
from glutamine by glutaminase a) Glutamine synthetase is a mitochondrial enzyme
enzyme. Most of this ammonia is used present in many tissues as kidney and brain.
in regulation of Acid base balance. b) Glutamine has the following functions:
3. Purines and pyrimidines metabolism. 1) Regulation of acid base balance: glutamine is
4. Various nitrogenous compounds e.g.: deaminated by glutaminase, releasing ammonia
monoamines that act as again. Ammonia is used in regulation of acid base
neurotransmitters. balance by the kidneys.
5. In intestine: ammonia is produced by 2) Removes the toxic effect of ammonia In brain:
the action of bacterial enzymes on: Ammonia + Glutamate → Glutamine.
a) Dietary amino acids. 3) Glutamine is the source of: N3 and N9 of purines
b) Urea secreted into the intestine. bases.
4) Glutamine is used in detoxication of phenyl acetic
acid (a toxic substance).
3. Formation of urea: It is the main pathway by
which the body can get rid of ammonia.
4. Excretion in urine

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UREA
DEFINITION
- Urea (H2N-CO-NH2) is the main end product of protein (amino acids) metabolism.
- Urea formation is the pathway through which the liver can convert toxic ammonia into non-toxic
urea.
SITE OF UREA FORMATION
1. Liver is the only site for urea formation.
2. Then urea is transported in the blood to the kidney to be excreted in urine (urine urea is
20-40 g/day).
PLASMA UREA
1. Plasma urea: is 20-50 mg/dl.
2. Diagnostic importance of plasma urea determination:
a) Measurement of plasma urea is one of the kidney function tests.
b) In kidney diseases as in renal failure, kidney fails to excrete urea → High blood urea
concentration (uremia).
UREA FORMATION
It is also called Krebs’ Henseleit cycle.
SITE: Liver.
1. The first two reactions occur in mitochondria where other reactions occur in cytosol.
2. Six amino acids share in urea cycle: ornithine, citrulline, arginosuccinate, Aspartate. And
Arginine. The 6th one is N-acetyl glutamate that acts as allosteric activator of Carbamoyl
phosphate synthase I.
STEPS
1. Formation of Carbamoyl phosphate:
a) This reaction occurs in mitochondria.
b) It needs CO2 (a product of citric acid cycle), ammonia (a product of deamination of glutamate)
and phosphate (from ATP).
c) This reaction is catalyzed by Carbamoyl phosphate synthase I. It needs magnesium (Mg) ions,
manganese (Mn++) and N-acetyl glutamate as activators.
d) 2 ATP molecules are used in this reaction, one to provide phosphate and the other to supply
energy.
2. Formation of citrulline:
a) This reaction also occurs in mitochondria.
b) Carbamoyl phosphate reacts with ornithine, in the presence of ornithine transcarbamoylase
enzyme producing citrulline.
c) Citrulline then passes to cytosol.
d) Ornithine is regenerated with each turn of urea cycle.
3. Formation of arginosuccinate:
a) Citrulline reacts with Aspartate in the cytosol to form arginosuccinate.
4. Cleavage of arginosuccinate:
a) It is cleaved into Arginine and Fumarate.
5. Cleavage of Arginine into ornithine and urea:

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a) Ornithine then passes to the mitochondria to start a new cycle.
b) Urea passes to the blood to be excreted by the kidney in urine.

• Three ATP molecules and four high-energy phosphate bonds are utilized in the reactions.
• Sources of different atoms of urea (H2N-CO-NH2):
1. 1st Nitrogen atom: from ammonia.
2. Carbon atom: from CO2.
3. 2nd Nitrogen atom: from Aspartate.

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AMMONIA INTOXICATION
Definition: Excess ammonia which is toxic to the central nervous system.

Symptoms: Include:
A. Flapping tremors, slurring speech, blurring vision and vomiting in infancy.
B. High concentration of ammonia may cause coma and death.

Types and causes of hyperammonemia

Acquired hyperammonemia Inherited hyperammonemia
1- Liver cell failure: The diseased liver Result from genetic deficiency of one of five
cells cannot convert ammonia into enzymes of urea cycle → Failure to synthesize
urea. urea → Hyperammonemia during the first week
2- Renal failure after birth → Mental retardation.
3- Shunt operation between portal and Type I Car. Ph. synthetase I.
systemic circulation. Type II Transcarbamoylase.
4- Collaterals between portal and Ctrullinemia Arg.succ.synthetase
systemic circulation due cirrhosis of Argininosuccinuria Arginosuccinase
liver by bilharziasis , hepatitis etc. Argininemia Arginase

Mechanism of ammonia intoxication:

- At normal blood ammonia level, any ammonia reaches the brain incorporated into glutamine
formation by glutamine synthetase enzyme.
- In cases of hyperammonemia, ammonia reacts not only with glutamate, but also with α-
Ketoglutarate by glutamate dehydrogenase enzyme. This depletes α-Ketoglutarate which is an
essential intermediate of citric acid cycle → Decrease in ATP and energy production →
symptoms of ammonia intoxication → coma.

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FATE OF α -KETO-ACIDS

- The α-ketoacid (the carbon skeleton) remaining after the removal of the amino group (NH2) by
transamination and deamination of amino acids may undergo:
A. Reamination: by ammonia (NH3) to form again the corresponding amino acid (by
glutamate dehydrogenase).
B. Catabolized to form seven products: pyruvate, acetyl CoA, acetoacetyl CoA, Fumarate,
oxaloacetate, α-Ketoglutarate and Succinyl CoA.
C. These products enter different pathways which lead to:
1. Synthesis of glycogen or glucose.
2. Synthesis of lipids.
3. Complete oxidation into CO2 and H2O.

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METABOLIC CLASSIFICATION OF AMINO ACIDS

Note

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CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS

GLYCINE
- Glycine is non-essential - glycogenic amino acid.
SYNTHESIS AND FATES
Glycine synthase
1- DENOVO: CO2 + NH2 + H2O GLYCINE
Glycine cleavage system

2- SERINE:

Hydroxy Methyl Transferase

Threonine aldolase
3- THERIONINE: THERIONINE GLYCINE + Acetaldehyde

4- GLYOXILIC ACID: BY REAMINATION

Functions Glycine is the precursor for:

- Heme - Hippuric acid - Glutathione - Glyoxylic acid
- Purine bases - Bile salts - Collagen -Creatine - Serine - Neurotransmitter
1. Heme: is the pigment, which combines with globin protein to form hemoglobin.
- Glycine reacts with Succinyl CoA to form a substance called amino levulonic acid (ALA) a reaction
needs pyridoxal phosphate. ALA is finally converted to heme.
2. Hippuric acid:
- Glycine conjugates with the toxic compounds like benzoate (an additive used to preserve foods)
to form the non-toxic hippuric acid. This occurs in the liver.
3. Glyoxylic acid
- Synthesis: Glyoxylic acid is formed from glycine by 2 mechanisms:
oxidative deamination and transamination:
- Fate of Glyoxylic acid:
a) Formation of formate: (by oxidative decarboxylation).

b) Formation of glycine: By Reamination (transamination).

- Primary hyperoxaluria:
- Def: It is a metabolic disease ccc by excessive excretion of Oxalate unrelated to dietary intake of
oxalate. This leads to formation of urinary oxalate stones.
- Complication: This condition usually ends by death in early life from either renal failure or
hypertension.
- Causes: failure of conversion of Glyoxylic a. into formate or glycine. leads to oxalate formation.

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- Glycinuria
- Def: It is a rare dominant x-linked disease ccc by excess urinary excretion of glycine.
- Complication: It leads to formation of oxalate renal stones.
- Causes: is due to defect in renal tubular reabsorption of glycine.

4. Glutathione: It is also called “γ-glutamyl, cysteinyl glycine”.

- Structure: Glutathione is a Tripeptide formed of three amino acids: glutamate, cysteine and
glycine.
- Synthesis: It is synthesized in two Glutathione steps catalyzed by (γ-glutamyl cysteine synthetase
and glutathione synthetase).
- Forms of glutathione:
- Two Forms are present: reduced (G-SH) and oxidized (G-S).
*-SH group indicates the sulfhydryl group of the cysteine and it is the most active part of the
molecule.
- Functions of glutathione:
1- Defense mechanism against certain toxic compounds (Detoxification).
2- Absorption of amino acid: glutathione has a role in transport of amino acids across
intestinal cell membrane..
3- Protect against cell damage and hemolysis of RBCs: Glutathione breakdown the
hydrogen peroxide (H2O2) which causes cell damage and hemolysis.
4- Activation of some enzymes.
5- Inactivation of insulin hormone.
5. Bile salts:
- These are sodium and potassium salts of glycocholic acid.
- Glycine is conjugated to cholic acid to form glycocholic acid.
6. Purine bases:
- Carbon atoms NO. 4, 5 and nitrogen atom NO. 7 are derived from glycine.

7. Collagens:
- Collagens are the main proteins of connective tissue.
- All collagen types have a triple helical structure.
- Each helix is formed of 3 amino acids.
- Glycine is present at every third position.

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8. Creatine (N-methyl-guanidoacetate):
- Synthesis of Creatine: It is synthesized from three amino acids: glycine, arginine, and
methionine. This occurs by two reactions in kidney and liver.
a) In kidney: the first reaction is transamdination i.e. transfer of guanido group, H2N-[C=NH]-
NH2 from Arginine to glycine to form guanidoacetate.
b) In liver: the second reaction is Transmethylation i.e. transfer of methyl group from S-
adenosyl-methionine to guanidoacetate to form methyl guanidoacetate

- Functions of Creatine:
- Creatine is phosphorylated to Creatine phosphate this occurs in muscles.
- Creatine phosphate acts as a store of high energy phosphate in muscles and used during
muscle exercise (as it can give phosphate to ADP to form ATP).
- Creatine kinase enzyme (CK): Also called Creatine phospho kinase (CPK):
- This enzyme catalyses the formation of creatine phosphate. Present in 3 isoenzymes
1) CK-MM: from skeletal muscles and its serum level is elevated in muscle disease
2) CK-MB: mainly from heart muscle and its serum level is elevated in recent myocardial
infarction.
3) CK-BB: derived from brain and its serum level is elevated in damage of brain cells.
- Degradation of Creatine phosphate → (gives creatinine):
a) Creatine phosphate loses water and phosphate molecules to form a substance called
creatinine (= anhydrous Creatine).
b) Creatinine is the end product of Creatine metabolism and is normally rapidly removed from
the blood and excreted by the kidney in urine.
- Diagnostic importance of determination of plasma creatinine:
a) Estimation of plasma creatinine (0.6 - 1.2 mg/dl) is used as kidney function test.
b) High blood creatinine (and urea) levels are sensitive indicators of renal failure.
9. Serine:
- Methylene H4 folate is used as donor of one carbon fragment (-CH2OH).
- It gives this carbon to glycine to form serine. The reaction is reversible.
10. Neurotransmitter: acts as an inhibitory transmitter in spinal cord and medulla
11. Catabolism of glycine: by enzyme called: glycine cleavage system

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PHENYLALANINE
- Phenylalanine is a Ketogenic and glycogenic essential amino acid.
- Functions: phenylalanine is the precursor for Tyrosine. In liver as follows:

- This reaction needs phenylalanine hydroxylase enzyme and tetrahydrobiopterin as coenzyme.

This results in the formation of dihydrobiopterin (DHB) which must be regenerated by
dihydrobiopterin reductase enzyme with NADPH + H as coenzyme.
- Deficiency of either phenylalanine hydroxylase or dihydrobiopterin reductase results in a
disease called: PHENYLKETONURIA.
- Definition: It is inherited deficiency of phenylalanine hydroxylase enzyme.
Atypical phenylketonuria: deficiency of dihydrobiopterin reductase enzyme.
- Effects (signs and symptoms):
1) Mental retardation. (By inhibit of pyruvate translocase enzyme)
2) Increased blood phenylalanine: due to inability to hydroxylate phenylalanine to tyrosine. &
converted it to phenylpyruvate and phenyllactate, which excreted in urine.
3) Failure to walk and talk. 4) Hyperactivity and tremors.
5) Failure to grow. 6) An Intelligence Quotient (IQs) 7) Skin lesion e.g. eczema.
- Frequency of phenylketonuria: is 1 in 10,000 live births.
- Diagnosis of phenylketonuria:
a) Infants are screened at birth (4th day) by measuring blood phenylalanine by a test called
Guthrie test, a bacterial assay for phenylalanine.
- Prevention of phenylketonuria:
a) Any infant proved to have abnormal high level of blood phenylalanine, should feed milk
containing very low amount of phenylalanine.
b) This regimen of diet is maintained up to 6 years of age when a high concentration of
phenylalanine has no longer effect on brain cells.

TYROSINE

- Tyrosine is a Ketogenic and glycogenic non-essential amino acid.

- Tyrosine becomes essential in case of deficiency of phenylalanine hydroxylase.
Functions Tyrosine is the precursor for: CMT
1- Catecholamines. 2- Melanin pigments. 3- Thyroid hormones.

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CATECHOLAMINES
These are dopamine, nor-epinephrine and epinephrine.

SYNTHESIS OF CATECHOLAMINES:
They are synthesized from tyrosine at storage
sites: adrenergic neurons and adrenal medulla.
- In neurons: nor-epinephrine and dopamine
are synthesized from tyrosine as follows:
1) Tyrosine is first hydroxylated to form 3, 4
dihydrophenylalanine (DOPA).
2) DOPA is then decarboxylated to dopamine,
which is hydroxylated to nor-epinephrine by
dopamine hydroxylase.
- In adrenal medulla:
1) Synthesis of catecholamines is similar to
synthesis in neurons.
2) In addition adrenal medullary cells, contain
phenylethanolamine N-methyltransferase
(PNMT). This enzyme catalyzes the conversion
of nor-epinephrine to epinephrine [by
Transmethylation].

REGULATION OF SYNTHESIS:
Tyrosine hydroxylase is the key enzyme. It is inhibited by
feedback inhibition by either dopamine or nor-epinephrine.

CATABOLISM OF CATECHOLAMINES: by 2 enzymes:

1) Monoamine oxidase (MAO): present mainly in the mitochondria of adrenergic nerve
2) Catechol-ortho-methyl transferase (COMT): which is present in all tissues, with high
concentration in the liver and kidney, but not found in the nerve endings.

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2-MELANIN PIGMENTS
SYNTHESIS OF MELANIN
In the skin, melanins are synthesized in melanocytes (pigment forming cells) by tyrosine
hydroxylase (tyrosinase) enzyme.

FUNCTIONS OF MELANIN
a) Melanins are pigments present in many tissues particularly in the iris, hair and skin.
b) Melanins are synthesized to protect underlying cells from the harmful effects of sunlight.

3. THYROID HORMONES

SYNTHESIS OF THYROID HORMONES

a) Synthesis and release of T3 and are stimulated by (TSH).
b) TSH secretion is under control of thyrotropin releasing hormone (TRH) which is a Tripeptide
hormone produced in the hypothalamus.
- By feedback mechanism: Increased levels of plasma T3 and T4 inhibit the secretion of TRH from
hypothalamus and TSH from pituitary gland.

STEPS OF THYROID HORMONES SYNTHESIS

1) The thyroid gland contains many follicles, each composed of a shell of single layered cells
surrounding a central space filled with glycoprotein called: thyroglobulin (TG).
2) Thyroglobulin contains about 150 tyrosine residues.3) Iodide ions (I-) can be taken up by thyroid
cells and oxidized into higher value state (positive ions, I+). This needs H2O2 and thyroid
peroxidase enzyme.
4) I+ is then incorporated into the tyrosine residues of TG.
5) The resulting Monoiodotyrosine and Diiodotyrosine residues react together to give one of the
following compounds:
a. Tetraiodotyrosine {thyroxin, T4}. b. Triiodotyrosine {T3}. c. Reverse {rT}.
6) Both T3 and T4 are biologically active, while rT3 is biologically inactive.
7) Enzyme hydrolysis of thyroglobulin releases free T3 and T4 into the plasma.

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FUNCTIONS OF THYROID HORMONES:

a) They increase heat production and oxygen consumption in most tissues through stimulation of
ATPase activity.
b) They regulate the growth of long bones (together with growth hormone).
c) They affect protein synthesis through stimulation of DNA in the nucleus of cells.
d) They increase catecholamine effect.
• Plasma T3 and T4:
a) In the plasma 99.95% of T3 and T4 are transported in association with 2 proteins:
1) Thyroxin binding globulin (TBG). 2) Thyroxin binding prealbumin.
b) About 0.05 % of T3 and T4 are Free T3 and T4 “active” hormones in the plasma.
Hyperthyroidism
Hypothyroidism (thyrotoxicosis)
- Def: ↓ amounts of free T3 or T4. - Def: ↑production of T3 or T4
- Cause: thyroid failure - Cause: Most cases are due to
can be due to disease of the pituitary or hypothalamus. Graves disease which results
- The thyroid hormones insufficiency during intrauterine from the production of
fetal life results in a disease shows abnormal physical antibodies that activate TSH
development and mental retardation (cretinism). production and in turn produces
Measurement of T3, T4 and TSH must be done for every excessive amounts of T3 and T4.
newly born infant These antibodies are called:
- If the disease occurs later in life, it is called: Thyroid-stimulating IgG (TSI).
(myxodema),
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CATABOLISM OF PHENYLALANINE AND TYROSINE

The carbon skeletons that have left after the removal of amino groups of both phenylalanine
and tyrosine may catabolize to form Fumarate (glycogenic) or acetoacetate (Ketogenic).

INBORN ERRORS OF TYROSINE METABOLISM

1- Hereditary tyrosinemia (tyrosinosis):
- Def: It is inability to metabolise tyrosine and p-hydroxy phenylpyruvate.
- Cause: deficiency of tyrosine α-Ketoglutarate transaminase and p-hydroxy-phenylpyruvate
oxidase enzymes
- Forms of tyrosinemia:
a) Acute: where there is diarrhea, vomiting and failure to grow. Death
from liver failure occurs within 7 months.
b) Chronic: occurs later in life. Liver cirrhosis and hepatic carcinoma are common. There is also a
mild mental retardation. For unknown cause methionine level may be high.
- Prevention and treatment:
- Feeding the affected infant and children a diet containing very low levels of tyrosine and
phenylalanine (precursor of tyrosine).
2. Alkaptonuria:
- Def: benign disease resulting from deficiency of homogentisate oxidase enzyme.
- Effects: Homogentisate increases and causes:
a) Deposition in joints causing arthritis.

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b) Deposition in connective tissue causing generalized pigmentation (ochronosis).
c) Excreted in large amounts in urine, that is oxidized in the air giving the dark urine
3. Albinism:
- Def: hereditary deficiency of tyrosine hydroxylase enzyme in melanocytes. - Effects:
defective synthesis of melanin pigments. Eye, skin and hair are affected.
- Types of albinism: according to the site affected:
a) Eye: ocular albinism. b) Skin: cutaneous albinism.
c) Eye and skin: oculo-cutaneous albinism.

Tryptophan
- It is glycogenic and ketogenic essential amino acid.
- Functions: Tryptophan is the precursor of: SMNI
1. Serotonin. 2. Melatonin. 3. Niacin (nicotinic acid) 4.Indole and skatole.

SEROTONIN
Also called 5-hydroxytryptamine.
SYNTHESIS OF SEROTONIN
- Tryptophan is hydroxylated in a reaction similar to that of phenylalanine.
The product 5-hydroxytryptophan is decarboxylated to serotonin.
• Storage sites of secretion & Functions of serotonin::
a) Hypothalamus and brain stem → Neurotransmitter: it is stimulatory one.
b) Pineal gland (body) → regulate circadian rhythm.
C) Argentaffin cells in intestinal mucosa→ Contraction of smooth muscle fibers.
d) Platelets → Vasoconstriction.
CATABOLISM OF SEROTONIN
- Serotonin undergoes oxidative deamination by monoamine oxidase (MAO).
The resulting compound, 5-hydroxyindol acetic acid is excreted in urine.
- Certain substances can inhibit MAO enzyme e.g. iproniazide drugs. This causes increase of
serotonin, a stimulatory transmitter in brain. These drugs are used in treatment of psychic
conditions as depression.
Argentaffinoma (carcinoid syndrome):
- Def: malignant disease characterized by excessive production of serotonin
- Complication: ↓niacin synthesis → signs of pellagra developed, diarrhea and broncho-spasm
- Diagnosis: Urinary excretion of 5-hydroxyindol acetic acid is increased.

Melatonin
SITE OF SECRETION: pineal gland

SYNTHESIS OF MELATONIN:
a) It is synthesized in pineal gland, as the acetyl transferase needed for melatonin synthesis is
present in pined gland. Melatonin is synthesized from serotonin by acetylation followed by
methylation.
b) Melatonin is secreted only at night (dark). This is because the release of melatonin is inhibited
by light entering the eye and transmitted to the pineal gland by way of the CNS.

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FUNCTIONS OF MELATONIN
a) It inhibits gonadal functions.
b) It has sleep inducing effect.
c) It inhibits synthesis and secretion of other neurotransmitters: dopamine and GABA.
d) Regulation of circadian rhythm, being synthesized mostly at night.

NIACIN (NICOTINIC ACID)

SYNTHESIS OF NIACIN
a) It is synthesized in the course of tryptophan catabolism.
b) Every 60 mg tryptophan are converted into 1 mg niacin.
FUNCTIONS OF NIACIN
Niacin is a member of vitamin B complex, being synthesized in liver.
a) It is essential for synthesis of NAD and NADP coenzymes, which act as hydrogen carriers in
varieties of metabolic reactions.
b) Niacin lowers plasma cholesterol. This is because it inhibits the flow of free fatty acids (FFA) from
adipose tissue, which provides acetyl CoA essential for cholesterol synthesis.
PELLAGRA
a) This is a disease resulting from deficiency of niacin formation.
b) It results from deficiency of either niacin tryptophan, or pyridoxine.
c) It is the disease of 4Ds. These are diarrhea, dermatitis, dementia and death.

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INDOLE AND SKATOLE
1. These are putrefactive products of tryptophan produced by bacteria in large intestine.
2. Indole and skatole give the characteristic odor of stool.
3. Indole and skatole may be absorbed and go to the liver to be hydroxylated and conjugated with
sulphate and excreted in urine as salt forms:
- Potassium skatolxyl
- Sulphate and potassium indoxyl sulphate (=indican).
HARTNUP‘S DISEASE:
- Def: hereditary abnormality in tryptophan metabolism where the intestinal absorption and renal
tubular reabsorption of this amino acid are impaired.
- Characters: by pellagra skin rashes, psychiatric changes and mental retardation.
- There is excess excretion of tryptophan together with lysine and histidine in urine
(aminoaciduria).
- ttt: Administration of Nicotinamide usually relieves all symptoms except aminoaciduria.

GLUTAMIC ACID
- Glutamic acid in nonessential glycogenic amino acid.
- Functions of glutamic acid: Remove GEFN
1. Removal of amino group of most amino acids. 2. Glutathione synthesis
3. Glutamine synthesis 4. Gamma amino butyric acid (GABA).
5. Enzyme activator. 6. Folic acid synthesis. 7. Neurotransmitter.
➢ Removal of amino group of most amino acids: in the form of ammonia through
Transdeamination.
➢ Glutathione synthesis: (See glycine metabolism).
➢ Glutamine synthesis: (See fate of ammonia).
➢ Enzyme activator:
N-Acetyl glutamate activates Carbamoyl phosphate synthase I enzyme (see urea biosynthesis).
➢ Folic acid synthesis:
- Folic acid is a member of vitamin B-complex being composed of pteridine base, Para-amino
benzoic acid (PABA), and one or more glutamic acid residues.
- Function: acts as a carrier of one carbon units, which has important role in amino acid
metabolism and Purine and pyrimidines synthesis.
➢ Neurotransmitter:
Glutamate acts as excitatory neurotransmitter in all CNS neurons.
➢ Gamma amino butyric acid (GABA):
o Synthesis of GABA:
- It is synthesized from L-glutamate by L-glutamate decarboxylase in the presence of
pyridoxal phosphate as coenzyme.

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o Functions of GABA:
- It is an inhibitory transmitter in brain and spinal cord.
a) In the brain, GABA is a postsynaptic inhibitory transmitter.
b) In the spinal cord, GABA is pre-synaptic inhibitory transmitter.
o Catabolism of GABA:
- It is metabolized within the neurons to Succinate:

o Deficiency of GABA:
a) It may be due to deficiency of either: L-glutamate decarboxylase or
pyridoxal phosphate.
b) It causes convulsions especially in children.

ASPARTATE
- It is non-essential glycogenic amino acid.
- Functions of Aspartate: papun β
• Purine formation • Asparagine • Pyrimidines formation • Urea formation
• Neurotransmitter • β-Alanine
➢ Purine formation:
Aspartate is the source of N1 of Purine.
➢ Pyrimidines formation:
Aspartate is the source of N1, C4, C5 and C6 of pyrimidines.
➢ Urea formation:
Aspartate reacts with citrulline to form arginosuccinate.
➢ Asparagine formation:
• Functions:
a) It enters in the structure of some proteins e.g. oxytocin hormone.
b) It is a source of ammonia especially in plants.
➢ Neurotransmitter:
Aspartate acts as an excitatory transmitter on all CNS neurons.
➢ β-Alanine:
- In bacteria, decarboxylation of aspartic acid produces β-Alanine.
- In mammalian tissues β-alanine arises during catabolism of cytosine base.
- β-Alanine enters in the structure of: pantothenic acid, coenzyme A, carnosine, anserine and
homocarnosine.

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ARGININE
- It is glycogenic, semi-essential amino acid i.e. formed in amount not sufficient for body especially
in children and pregnant females.
- Functions of Arginine: CANU
• Creatine formation: see glycine metabolism.
• Arginine phosphate (Arginine — P): it is present in muscles and acts as a source of energy in
animals (invertebrate).
• Urea formation: see urea cycle.
• Nitric oxide: L-Arginine serves as a precursor of nitric oxide (NO).

1. NO is an intracellular signaling molecule and functions as neurotransmitter, smooth muscle

relaxant and vasodilator (through cGMP).
- NO synthase is a complex enzyme using 5 cofactors: NAD, FAD, FMN, heme and
tetrahydrobiopterin
2. Nitroglycerine (glyceryl trinitrate) is a powerful coronary vasodilator through increasing NO
formation.
3. Sildenafil (Viagra) is a drug that inhibits phosphodiesterase enzyme that converts cGMP into
GMP. This maintains the action of cGMP as smooth muscle relaxant and vasodilator and used as
a drug that maintains penile erection.

ORNITHINE
- It is a glycogenic, non-essential amino acid.
- Functions: Ornithine is important for:
➢ Urea formation.
➢ Detoxication:
Ornithine + Phenyl acetyl CoA (Toxic) → Phenyl acetyl ornithine (non-toxic).
➢ Spermidine and spermine formation: These are polyamines formed in prostate by ornithine and
methionine.
• Functions:
a) Cell proliferation (division) and growth.
b) Stabilization of intact cells, cell membrane and sub-cellular organelles.
c) They give the characteristic odor of semen.
d) Stimulation of DNA and RNA biosynthesis.
e) Inhibition of protein kinase enzyme.
f) In pharmacological doses, polyamines cause decrease in both blood pressure (hypotension) and
body temperature (hypothermia).

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• Biosynthesis:

• Catabolism:
a) Spermine is oxidized to Spermidine and putrescine.
b) Both are either excreted in urine or converted to CO2 and NH3.

PROLINE ANT HYDROXYPROLINE

- These are non-essential glycogenic imino acids.
- Functions of proline:
➢ Hydroxyproline synthesis:

➢ Collagen synthesis:
1. Proline and hydroxyproline are very rich in collagen.
2. Ascorbic acid deficiency leads to a weak collagen (scurvy).
• Catabolism of proline: gives glutamate.

CYSTEINE
- Cysteine is glycogenic, non-essential amino acid.
- Functions: It enters in the synthesis of:
• Glutathione • Taurine • Thioethylamine • Proteins • Detoxication
➢ Taurine:
• Synthesis:

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• Functions:
It combines with cholic acid to form taurocholic acid. Its sodium salt (sodium taurocholate) is one
of bile salts, which are Important for digestion, and absorption of lipids.
➢ Thioethylamine: A part of the vitamin: Pantothenic acid.
• Functions: it enters in the structure of:
a) Coenzyme A: It is a coenzyme, which is important in carbohydrates and lipids metabolism.
b) Acyl carrier protein (ACP): This is a component of fatty acid synthase enzyme.
• Synthesis:

➢ Protein synthesis: Cysteine is very important amino acid for some proteins as:
1. Keratins: simple proteins that are present in hair, nail, skin etc. Keratins are very rich in cysteine.
2. Many enzymes: e.g. glyceraldhyde-3-phosphate dehydrogenase contains in its active center -SH
group derived from cysteine.
➢ Detoxication: Cysteine is important for the detoxication of some aromatic compounds e.g.
bromobenzene.

CYSTINE
- Cystine (di-cysteine) is glycogenic, non-essential amino acid.
- Functions:
➢ A. Protein structure: The -S-S- group of cystine is important for tertiary and quaternary structure
of proteins e.g. insulin hormone has two -S-S- groups.
Cystinuria (cystine - lysinuria):
- Def: hereditary disease characterized by amino aciduria (excessive excretion of cystine together
with basic amino acids; lysine, Arginine, and ornithine.
- Cause: defective renal tubular reabsorption of these 4 amino acids. Cystine may precipitated in
renal tubules forming renal stones.

HOMOCYSTEINE
- Homocysteine test measures the amount of the amino acid in the blood.
- Homocysteine may get high levels when cholesterol, white blood cells, calcium, and other
substances (plaque) build up in blood vessels. This build-up may lead to a heart attack. Stroke.
And blood clots in the lungs (pulmonary embolism) or deep veins of the legs (deep venous
thrombosis).

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METHIONINE
i. Methionine is glycogenic, essential amino acid.
ii. Function: It enters in the synthesis of:
A. Cysteine synthesis: Through formation of Homocysteine, this reacts with serine to give cysteine.
B. Lipotropic factor: Methionine is one of lipotropic factors, which prevent fatty liver.
C. Spermidine and spermine: see ornithine metabolism.
D. S-Adenosyl methionine (SAM): The main methyl donor, used in
Transmethylation reactions.
Transmethylation reactions.
- Def: the transfer of active methyl group from a methyl donor to a methyl acceptor.
- Formation: SAM is a high energy compound resulting from a condensation of methionine with
ATP with hydrolysis of all phosphate bonds in ATP.

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- Catabolism: - After giving the methyl group to a methyl acceptor, SAM is converted to S-adenosyl
Homocysteine, which is then hydrolyzed to Homocysteine & adenosine.
- Homocysteine has two fates:
1) Synthesis of cysteine:
i- Homocysteine can combine with serine forming cystathionine by cystathionine synthtase
ii- Cystathionine is hydrolyzed to L-Homoserine and cysteine by cystathionase.
iii- Homoserine → α-Keto butyrate → oxidatively decarboxylated to form → Propionyl COA
→ Succinyl CoA → glucose.
2) Re-Synthesis of methionine:
i- Homocysteine can accept a methyl group from methyl tetrahydro-folate (Me-
H4-Folate) in a reaction requiring cobalamine (B12) as an intermediate cofactor.
- Examples: SAM SAH
1. Nor-epinephrine methyl-transferase epinephrine.
2. N-acetyl serotonin melatonin.
3. Ethanolamine Choline.
4. Guanido acetate Creatine.
5. Pyridine N methyl pyridine.
HOMOCYSTANURIA:
* This is a hereditary disease due to deficiency of cystathionine β-synthase
* Plasma methionine levels are elevated.
* There is excessi ve urinary excretion of Homocysteine and SAM
*sig and symptoms include: mental retardation, thromboses, osteoporosis and dislocation of
eye lenses.
*Treatment: feeding a diet low in methionine high in cysteine.

HISTIDINE
I. It is essential, glycogenic amino acid.
It is used for synthesis of: A. HISTAMINES
1. Functions: Histamine is secreted by mast cells as a result of allergic reactions or trauma. It has
the following functions: a) Vasodilatation. b)
Contraction of smooth muscles of bronchi. c) Stimulation of gastric secretions.
2. Synthesis:
Histamine is derived from histidine by decarboxylation. This reaction is catalyzed by either 2
different enzymes: a) Aromatic L-amino acid decarboxylase or
b) Histidine decarboxylase.
B. Ergothionine:
1. It is N-trimethyl, thiol histidine. 2. Ergothionine is an intracellular antioxidant naturally
occurring in plants and animals.
C. Carnosine and Anserine:
1. Carnosine is a substance results from conjugation of histidine with β-alanine.
2. Anserine is produced by methylation of carnosine.
3. Both are present in skeletal muscles and not in cardiac muscle.

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4. Functions:
a) Anserine and carnosine activate myosin ATPase enzyme.
b) They have antioxidant activity and have a role in copper metabolism.
- Catabolism of Hisidine: is deaminated to urocanic acid, which is converted to 4-imidazolone 5-
propionate. Hydrolysis of the later, gives N-formiminoglutamate (FIGlU) , which donates its
formimino group to tetrahydro-folate , leaving glutamate which is then converted to a-
Ketoglutarate.
a) FIGLU excretion test: Deficiency of folic acid + excretes increased amount of FIGIU in urine. It is
useful test of folic acid deficiency.

HISTIDINEMIA:
* This is a hereditary disease due to deficiency of histidase enzyme.
* It is characterized by mental retardation and speech defects.

SERINE
I. Serine is non-essential, glycogenic amino acid.
II. Serine is used for the synthesis of:
A. Phosphoprotein: The -OH group of serine residues present in proteins is the site
of etherification of phosphate to form phosphoprotein.
B. Sphingosine base: Serine reacts with palmityl CoA to form sphingosine base. It
enters in the structure of Sphingomyelin
C. Cysteine: Serine reacts with Homocysteine (derived from Adenosyl methionine) to form
cysteine.
D. Purine bases: n-carbon of serine enters in the formation of C2 and C5 of Purine
E. Glycine: Through the action of serine hydroxy methyl transferase.
F. Ethanolamine and choline: Serine, ethanolamine and choline are important constituents of
phospholipids.
Alanine and β-alanine
I. These are non-essential, glycogenic amino acid
ii. Alanine is important for:
A. Alanine -together with glycine- forms a major fraction of plasma amino acids.
B: Alanine is the main amino acid that is converted into glucose in liver through alanine-glucose
cycle.
G. Alanine is a major component of bacterial cell wall.
- β-Alanine is important for the synthesis of:
A. Pantothenic acid, anserine acid carnosine.
B. -Alanine does not enter in the formation of proteins.

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 PROTEINS METABOLISM 169

Threonine
I. It is essential, glycogenic amino acid.
II. Threonine is used for the synthesis of:
A. Phosphoproteins: Like serine, the -OH group of threonine is important for. the synthesis of
Phospho-proteins.
B. Glycine: Through the action of threonine aldolase enzyme.
LYSINE AND HYDROXYLYSINE
I. Lysine is an essential, ketogenic & glucogenic amino acid.
II. Lysine is important for Hydroxylysine synthesis:
A. Collagen synthesis: Lysine and hydroxylysine are very rich in collagen.
B. Carnitine synthesis: 1. It is 3-hydroxy, y-trimethyl amino butyric acid.
2. It is synthesized from lysine, at first by methylation (using S-adenosyl methionine), then
deamination and finally by removal of 2 carbons to give Carnitine.
3. Functions: Carnitine acts as a carrier, transporting long chain acyl CoA across inner
mitochondrial membrane. This is essential for fatty acid oxidation
BRANCHED CHAIN AMINO ACIDS
Valine - Leucine – Iso-Leucine
1. All are essential amino acids.
2. Valine is glycogenic, Leucine is Ketogenic and Isoleucine is glycogenic and Ketogenic.
3. All enter in the formation of body proteins.
- Catabolism:
- The transamination of the branched chain amino acids occurs mainly in muscle, brain and adipose
tissue. Liver is deficient in transaminase required for their transamination.
- The α-ketoacid, which result from the transamination reactions are oxidatively decarboxylated
by α- ketoacid decarboxylase to give acyl CoA that is less than a-keto acid by one carbon atom.
This reaction is similar to that catalyzed by pyruvate
dehydrogenase complex.
- The acyl CoA will be oxidized through several steps to give:
a) Succinyl CoA: this is for valine (glycogenic).
b) Acetyl CoA, acetoacetyl CoA: this is for Leucine (Ketogenic).

MAPLE SYRUP URINE DISEASE:

a) Definition: It is accumulation of α-ketoacid of branched chain amino acids and their excretion in
urine.
b) Cause: it results from deficiency of oxidative decarboxylation of α-ketoacid.
c) Effects: 1. Mental retardation. 2. Urine has a maple syrup odor or burnt sugar.
3. Children do not usually live more than 1 year.
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170 PROTEINS METABOLISM

PROTEIN DISEASE

DISEASE DEFICIENCY OF EFFECT

- ↓renal reabsorption of
- oxalate renal stones
GLYCINURIA glycine
- dominant x-linked disease
GLYCINE failure of conversion of
PRIMARY Glyoxylic acid into formate
- renal failure or
- Hypertension.
HYPEROXALURIA or glycine - death in early life
- mental retardation,
METHIONINE HOMOCYSTANURIA cystathionine β-synthase - thromboses,
- osteoporosis and

- Mental retardation
- Failure to walk and talk.
- phenylalanine hydroxylase
- Hyperactivity and tremors
PHENYLALANINE PHENYLKETONURIA or
- An Intelligence Quotient
- dihydrobiopterin reductase
(IQs)
-Skin lesion e.g. eczema

- tyrosine α-Ketoglutarate
- Liver cirrhosis and
transaminase and
TYROSINOSIS - p-hydroxy-phenylpyruvate
- hepatic carcinoma
- mental retardation
oxidase
- arthritis
TYROSINE ALKAPTONURIA Homogentisate oxidase - ochronosis
- dark urine
Defective synthesis of
ALBINISM - tyrosine hydroxylase melanin pigments. Eye, skin
and hair are affected
HARTNUP‘S - intestinal absorption
- pellagra skin rashes,
TRYPTOPHAN - renal tubular reabsorption
- psychiatric changes and
DISEASE mental retardation

BRANCHED CHAIN MAPLE SYRUP oxidative decarboxylation of

- Mental retardation. -
Urine has a maple syrup
AMINO ACIDS URINE DISEASE α-ketoacid
odor or burnt sugar

↓ renal reabsorption of - Crystaluria

CYSTINUREA cystine - stone formation
CYSTINE Defect of transport system of
CYSTINOSIS tyrosine.

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 ‫‪PROTEINS METABOLISM‬‬ ‫‪171‬‬

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 Vitamins
❖ Definitions:
• Vitamins: Are organic compounds that:
1. Essential for many biochemical reactions.
2. Many of them act as coenzymes.
3. They do not enter in the structure of the tissues or oxidized by them.
4. They are needed in very small amounts.
• Provitamins:
- These are precursors of vitamins that converted into vitamins inside the body e.g.
carotenes are Provitamin A.
• Vitamers:
- These are different forms of one vitamin e.g. Vitamin D has 2 Vitamers; D2 and D3.
❖ CLASSIFICATION OF VITAMINS: According to the solubility, vitamins are classified into:
• A. Fat soluble vitamins: These are vitamins: A, D, E, and K.
1. They are soluble in fat solvents.
2. They need bile salts for absorption.
3. They can be stored in the body.
• B. Water soluble vitamins: These are vitamins: C and B complex group.
1. They are soluble in water.
2. Most of them are not stored in the body.

DR. Mahmoud Ettaweel 01004486188 173

 Fat soluble vitamins
Vitamin A (retinoids)
Anti xerophthalmic
• Structure:
1. Carotenes are the Provitamin A.
2. Retinol, retinal and retinoic acid are the forms (Vitamers) used by the body.
• Sources:
▪ Animal sources:
a) Liver, eggs and milk fat. b) Fish liver oils e.g. shark liver oil.
▪ Plant sources:
a) Vitamin A is present in plants as (carotenes) (= Provitamin A).
b) Carotenes (α, β and γ):
1) Present in carrots, potato and tomatoes.
2) Are yellow pigments containing β-ionone ring at one end of the molecule.
3) Are converted into vitamin A (retinal aldehyde) in the intestine.

• Metabolism:
- Diet contains retinol esters and β-carotene.
- Retinol esters are hydrolyzed into fatty acids and retinol that absorbed into
intestinal mucosal cells.
- β-carotene is absorbed and converted into retinal (by β-carotene di-oxygenase
enzyme). Retinal then converted into retinol.
- In the intestinal mucosal cells, retinol re-esterifies with fatty acid to form retinol
ester.
- Retinol esters are absorbed through lymph vessels into general circulation and
transported to the liver, where 90% of the body’s vitamin A is stored.
- When the body cells need vitamin stored retinol esters are hydrolyzed and free
retinol binds with a protein formed by the liver called retinol binding protein RBP).
BP caries retinol to the retina and target cells.

DR. Mahmoud Ettaweel 01004486188 174

 a) In retina, retinols converted into retinal that essential for vision.
b) In other target cells retinol is oxidized into retinoic acid which binds to nuclear
receptors. Retinoic acid receptor-complex stimulates genes. This mode of action
is similar to hormones.

DR. Mahmoud Ettaweel 01004486188 175

• Functions of vitamin A:
1. Vision
- Retinal is essential for night vision.
2. Reproduction:
- Retinol is essential for reproduction. It supports sperm formation
(spermatogenesis) in males and maintains fetal life in females.
3. Growth:
- Retinol is essential for normal growth and bone & teeth formation.
4. Maintenance of epithelial cells:
- Retinol and retinoic acid are essential for normal differentiation of epithelial cells.
This is important for smoothness of skin and mucus membranes.
- Retinol is also essential for intact cornea.
5. Retinoic acid: is important for
a) Glycoprotein synthesis.
b) Phospholipids synthesis in the lungs (lung surfactant).
6. Antioxidant (anticancer) action:
a) Retinoids and Carotenoids (carotenes) act as antioxidants and protect tissues
from toxic effect of some oxidants that may lead to epithelial tissue cancer.

• Vision:
a) The human retina contains two types of receptor cells for vision; cones and rods:
1) Cone cells are responsible for day vision and color.
2) Rod cells are responsible for vision in poor light e.g. at night.
b) Vitamin A is a component of a visual pigment (rhodopsin) present in cones and
rods.

DR. Mahmoud Ettaweel 01004486188 176

 c) Visual cycle:
1) Rhodopsin consists of protein called opsin bound to 11-cis retinal (double bond at
position 11 is in Cis form, while other double bonds are in Trans form).
2) When rhodopsin is exposed to dark light, 11 Cis retinal is converted into all Trans
retinal (all double bonds are in Trans form).
3) All Trans retinal changes the permeability of cell membrane of rod cells. This
allows the calcium ions to pass out of the cell membrane. This stimulates the nerve
impulse in optic nerve. Thus the brain perceives light.
4) Rhodopsin must regenerate for vision. All Trans retinal are, converted back to 11-
cis retinal. but this conversion is incomplete. This can be supplied from dietary
retinol, which is oxidized to give 11-Cis retinal.

DR. Mahmoud Ettaweel 01004486188 177

• Deficiency of vitamin A:
1. Eye:
- Night blindness (Nyctalopia): impaired dark adaptation.
- Xero-ophthalmia (Bitot spots): dryness and roughness of cornea.
- Keratomalacia: degradation of corneal epithelium.
- Blindness.
2. Growth retardation.
3. Skin and- mucus membranes: Roughness of skin and mucus membranes of
different body systems e.g. urinary system. This leads to infection.
4. Alopecia: loss of hair from the head or body.
• Requirements of vitamin A: 5000 IU/day.
• Excess vitamin A (overdose):
- It occurs when excessive vitamin A intake exceeds the capacity of RBP.
- Free retinol will release in blood with the following toxic effects:
- Headache - Nausea - Bone pain - Loss of hair.
Vitamin D (Calciferol)
1, 25 dihydroxycholecalciferol
Calcitriol
• Sources:
1. Ultraviolet rays of sun generate the D vitamins from the Provitamin ergosterol (in
plants) and 7-dehydrocholesterol (in human and animals)
2. Liver, egg, yeast and fish liver oils are rich in vitamin D.
• Structure and activation of vitamin D group:
1. Active vitamin D is a steroid hormone. It is synthesized and activated as shown in
the diagram.
• Functions of vitamin D: 1, 25 dihydroxycholecalciferol (calcitriol) acts as a hormone. It
has the following functions:
1. Normalization of serum calcium (9-11 mg/dl): Calcitriol maintains serum calcium
level through its effects on intestine, bones and kidneys.
a) On intestine: it stimulates synthesis of calcium binding protein (calbindin) that
responsible for calcium absorption.
b) On bones: It stimulates calcium resorption from bones.
c) On kidneys: It increases renal tubular reabsorption of calcium.
2. Mineralization of bones:
a) In small doses: calcitriol helps bone mineralization by providing Ca+ and p+.
b) In large doses: The reverse occurs, where Ca+ and p+ move from bone to blood.
3. Absorption of phosphate from intestine: It increases also tubular reabsorption of
phosphate.
4. Synthesis of osteocalcin:
- It is calcium binding protein present in bones.
- It is important for proper mineralization of bones.
- 1, 25(OH)2 D3 stimulates its synthesis in the form of pro- osteocalcin.
- Note: 24, 25 dihydroxycholecalciferol is biologically inactive.

DR. Mahmoud Ettaweel 01004486188 178

DR. Mahmoud Ettaweel 01004486188 179
• Regulation and mechanism of action of 1,25 D3
(calcitriol):
1. Hypocalcemia → release of parathyroid hormone
→ Activation of renal 1-hydroxylase enzyme →
Conversion 25 (OH) D3 into 1, 25(OH)2 D3.
2. Hypophosphatemia → Direct Activation of renal 1
hydroxylase enzyme → Conversion of 25 (OH) D3
into 1, 25(OH)2 D3.
3. In the intestinal mucosal cells, 1, 25(OH)2 D3 is
bound to specific cytoplasmic receptors forming a
complex. This complex enters the nucleus,
stimulating DNA to produce specific mRNA. This
mRNA is responsible for synthesis of calcium
binding protein (calbindin) which helps the
absorption of calcium.
4. Absorption of phosphate is similar to the
previous mechanism but it occurs secondary to
calcium absorption.
• Deficiency of vitamin D: Causes demineralization of
bones that leads to rickets and Osteomalcia:
- Rickets in children: characterized by bone
deformities.
- Osteomalcia in adults: characterized by bone
fractures.
- Renal rickets: In chronic renal failure there is a
deficient formation of active form of the vitamin D3
(decreased 1-hydroxylation of the vitamin). This
leads to renal rickets.

• Requirements: 400 IU/day.

• Excess vitamin D: (overdose or hypervitaminosis D):
This leads to abnormal calcification of tissues and deposition of calcium and
phosphate in different systems e.g. renal stones.

DR. Mahmoud Ettaweel 01004486188 180

 Vitamin E (Tocopherols)
Tocotrienols
• Structure
- There are four types of tocopherols α, β,
γ and δ.
- All contain tocol ring.
- The most active member is α tocopherol.
- γ and δ tocopherols differ from α
tochopherol in number and position of —
CH3 groups attached to the tocol ring.
• Sources: Vegetables and seed oils. It is present also in fish liver oils.
• Functions of vitamin E:
1. Antioxidant: Vitamin E prevents non-enzymatic oxidation of cell components (e.g.
polyunsaturated fatty acids, DNA and cell membranes) by molecular oxygen or free
radicals.

2. Vitamin E removes peroxide formation in polyunsaturated fatty acids.

3. Protection against heart disease.
- Vitamin E acts as antioxidant. It prevents oxidation of LDL.
- Oxidized LDL causes heart disease.
• Deficiency: Occurs usually in premature infant :
1. Hemolysis of RBCs and anemia: due to lack of protection against peroxides.
2. Muscle breakdown.
3. Acanthocytosis (spiky RBCs). 4. Peripheral neuritis.
5. Ataxia: is a neurological sign consisting of lack of voluntary coordination of muscle
movements.
6. Retinitis pigmentosum.
• Requirements: 15 IU/day.

Vitamin K (anti hemorrhagic V)

DR. Mahmoud Ettaweel 01004486188 181
 Phylloquinone, menaquinone
• Structure: There are three forms (Vitamers) of vitamin K: K1, K2 and K3.
1. The difference between K1 and K2 lies in side chain R.
2. K3 is synthetic vitamin and has no R side chain.
• Sources:
1. The main source of vitamin K is the intestinal bacteria. They produce Vitamin K2
2. Vitamin K1 is present in plants.
3. Vitamin K3 is synthetic. It is water soluble and more potent than K1 & K2.
• Functions of vitamin K :
1. Synthesis of some blood clotting factors in liver: prothrombin (factor II), and
factors VII, IX and X (1972).
2. Synthesis of osteocalcin (calcium binding protein) in bones.
• Mechanism of action
- Prothrombin is a protein formed in the liver as inactive form called prothrombin
precursor. It contains 10 glutamic acid residues.
- Carboxylation of these glutamic acid residues into γ-carboxy glutamate converts the
molecule into active thrombin.
- The same carboxylation reactions occur to factors VII, IX and X.

• Deficiency of vitamin K:
- It leads to impairment of blood clotting.
- Deficiency of vitamin K is rare because intestinal bacteria synthesize it.
- Vitamin K deficiency occurs in the following conditions:
a) New born infant because their intestine is sterile.
b) Prolonged use of antibiotic as they kill intestinal bacteria.
c) Liver diseases:
1) Liver is the site for prothrombin synthesis.
2) Liver forms bile salts which are essential for vitamin K absorption.
d) Prolonged use of Dicumarol and Warfarin (anticoagulants) as they act as
competitive inhibitors with vitamin K for its site of action.

Water Soluble Vitamins

DR. Mahmoud Ettaweel 01004486188 182
 Vitamin C = (L-Ascorbic acid)
• Sources:
- Fruits especially citrus fruits (lemon, orange), melon and strawberry.
- Vegetables especially green leafy vegetables as lettuce, tomatoes, potatoes, raw
cabbage and green peppers.
- Guava is very rich in vitamin C.
• Structure:
- Animal tissues contain 90% L-
ascorbic acid and 10% dehydro L-
ascorbic acid. Both forms are active.
- Further oxidation gives inactive
form called L-diketogulonic acid →
oxalic acid.

• Chemical properties:
- Ascorbic acid is acidic because it contains two enol groups (C-OH).
- Vitamin C is the most labile vitamin in food i.e. easy to be destroyed. Much of its
activity is lost through oxidation during preparation, cooking and storage.
• Functions of vitamin C:
1. Formation of collagen protein:
a) Ascorbic acid is essential for the conversion of the Procollagen (immature
collagen) into collagen. Procollagen is a protein containing proline and lysine.
Hydroxylation of both amino acids is catalyzed by hydroxylase enzymes and by
vitamin C as a coenzyme. This converts Procollagen into collagen.
b) Collagen is essential for the synthesis of connective tissue, bone, cartilage and
teeth.
2. Absorption and mobilization of iron: Ascorbic acid is a potent reducing agent,
keeping iron in ferrous state:
3. Acts as co-enzyme for many hydroxylase enzymes in the pathway of:
a) Bile acids synthesis: by 7 α hydroxylase.
b) Osteocalcin synthesis: osteocalcin is calcium binding protein in bones.
c) Carnitine synthesis: carnitine is a substance formed in the muscle. It stimulates
fatty acid oxidation in mitochondria.
d) Epinephrine synthesis: by hydroxylase required for conversion of tyrosine into
epinephrine.
4. Antioxidant action: Vitamin C acts as antioxidant and protect tissues from toxic
effect of some oxidants that may lead to cancer.

• Deficiency: → (scurvy):

DR. Mahmoud Ettaweel 01004486188 183

 - Vitamin C store is sufficient for 3 months. If this store is depleted a disease called
scurvy will result. It is characterized by:
1. Manifestations due to decreased collagen formation:
a) Bleeding into gum, muscles, joints, kidneys, GIT and pericardium.
b) Defective formation of bone and teeth.
c) Defective healing of wounds.
d) Necrosis of gums and loss of teeth.
2. Anemia: due to decreased absorption of iron and bleeding.
3. Manifestations due to decreased neurotransmitters (epinephrine):
a) Behavioral changes.
b) Severe emotional disturbances.
4. Manifestations due to decrease carnitine and fatty acids oxidation:
a) General weakness.
• Excessive vitamin C:
- Intake of high doses of vitamin C produces hyperoxaluria (increased oxalate in
urine) and may lead to stone formation.
• Requirements:
- 60 mg/day.
The B complex vitamins
• Introduction:
A. These are a group of vitamins of different chemical molecules. They were put
together in one group because:
1. All are soluble in water.
2. All are present in the same sources. B vitamins are particularly abundant in
whole grain cereals, liver and yeast.
3. Due to their presence in the same foods: deficiencies of B vitamins are often
multiple rather than singular.
• Functions of vitamin B complex:
1. All B-complex vitamins serve as coenzymes in enzymatic reactions.
2. Folic acid and B12 act as coenzymes in hematopoiesis (formation of red blood cells).
• Absorption of vitamin B complex:
1. The B vitamins are absorbed in the intestine and transported in the portal
circulation.
2. The tissue stores of most B vitamins are minimal. The depletion occurs over several
weeks in response to dietary restriction or increased the requirements as in
pregnancy. Body stores of folic acid and vitamin B12 are more extensive than other B
vitamins.

• Toxicity of vitamin B complex:

- Toxic effects are relatively uncommon, since excessive ingestion of water soluble
vitamins is followed by saturation of body stores and rapid loss of excess vitamins in
the urine.

DR. Mahmoud Ettaweel 01004486188 184

 Thiamin (vitamin B1)
• Sources:
1. Whole grain cereals legumes and yeast.
2. Unpolished rice and whole wheat bread.
• Structure:
1. Thiamin consists of a substituted pyrimidine ring
connected to a substituted thiazole ring through
a methylene bridge (CH2)
2. Active form of B1 = Thiamin diphosphate (TPP):
a) It is called also thiamin pyrophosphate.
b) Formation of TPP needs thiamin kinase enzyme
which is present in liver, red cells and nervous
tissue.
• Function
- TPP acts as coenzyme in two separate reactions in
carbohydrate metabolism. These are:
1. Oxidative decarboxylation of α- ketoacid:
(pyruvate, α-Ketoglutarate and ketoacids of
branched chain amino acids; Valine, Leucine and
Isoleucine) by:
a) Pyruvate dehydrogenase enzyme.
b) α-Ketoglutarate dehydrogenase (in citric acid
cycle, CAC).
- Note: These reactions produce energy and
CO2.
2. Transketolation reactions: by transketolase, in
pentose phosphate pathway.
3. Thiamin is also essential for the process of nerve
conduction and structure of nerve membrane.
Thiamin triphosphate acts as phosphate donor for
phosphorylation of sodium transport channel of
the nerve membrane.

DR. Mahmoud Ettaweel 01004486188 185

• Deficiency: Beriberi (Wernicke-Korsakoff syndrome)
1. ↓TPP → impaired conversion of pyruvate to acetyl CoA this leads to ↓ Energy
production → Impaired cellular functions epeciaIIy of nervous system → beriberi
2. Types of beriberi:
a) Acute beriberi (also called dry beriberi) characterized by:
1. Peripheral neuritis (numbness).
2. Muscle wasting (paralysis of the lower legs).
3. Mental confusion/speech difficulties.
b) Chronic beriberi: (also called wet beriberi) characterized by:
1. Heart failure.
2. Edema.
3. Dyspnea on exertion.
c) Infantile beriberi
- This type of beriberi is commonly found in children in developing countries.
Obvious signs and symptoms are crying, but not loudly and without tears.
Untreated, it can prove fatal within 24 hours.
• Requirements: 1.5 mg / day.
Riboflavin (vitamin B2)
• Sources:
1. Milk and milk products
2. Eggs, liver and green leafy vegetables.
• Structure:
1. It is formed of Flavin ring attached to ribitol (alcohol of ribose sugar).
2. Active forms of riboflavin.
a) Riboflavin enters in the structure of Flavin mononucleotide (FMN) and Flavin
adenine dinucleotide (FAD)
b) FMN is formed by phosphorylation of riboflavin by ATP (by intestinal flaviokinase
enzyme).
- FAD is formed by the transfer of an AMP moiety from ATP to FMN.

• Functions of B2:
1. Both FMN and FAD are coenzyme for flavor-enzymes. They act as hydrogen (or
electron) carriers in oxidation reduction reactions → FMNH2 and FADH2.
2.
DR. Mahmoud Ettaweel 01004486188 186
• Examples:

• Deficiency: B2 deficiency is not fatal. It is characterized by:

1. Ocular disturbances:
a) Photophobia i.e. abnormal sensitiveness of the eye to the light.
b) Vascularization of cornea.
2. Cheilosis (fissuring at the corners of the mouth).
3. Glossitis i.e. inflammation of tongue, which appears smooth and purplish.
4. Dermatitis i.e. inflammation of the skin.
• Requirements: 1.5 mg/day.
Niacin (nicotinic acid, B3)
• Sources:
1. Whole grain and cereals.
2. Milk, meat, liver, and yeast.
3. Niacin can be synthesized endogenously from the amino acid tryptophan:
a) Each 60 mg tryptophan can be converted to 1 mg niacin. This conversion
requires vitamin B6, as a co-enzyme.
b) Meat is rich in tryptophan, so it is important source of niacin.
c) Corn is poor in both niacin and tryptophan.
• Structure:
1. Niacin (nicotinic acid) is a pyridine derivative.
2. It is a nontoxic substance present in a toxic alkaloid nicotine of tobacco.
3. Active forms:
a) Niacin is converted to the active form Nicotinamide that enters in the structure of
Nicotinamide adenine dinucleotide (NAD) and Nicotinamide adenine dinucleotide
phosphate (NADP).
b) Nicotinamide, a derivative of nicotinic acid contains amide group.
• Synthesis of NAD and NADP:
- The formation of NAD and NADP occurs in cytosol of liver cells. NADP has similar
structure in addition to phosphate.
- NAD and NADP present in two forms oxidized and reduced. They undergo reduction
of pyridine ring by accepting a Hydride ion (H atom plus one electron).

DR. Mahmoud Ettaweel 01004486188 187

• Functions of niacin:
1. Formation of (NAD) and (NADP):
- These two coenzymes function as hydrogen carriers and they are essential for
many biochemical oxidation-reduction reactions.
- These reactions are important in carbohydrate, protein and lipid metabolism.
2. Lowering plasma cholesterol. Niacin can be used in treatment of high plasma
cholesterol and lipids. Niacin lowers plasma cholesterol concentration. This is
due to inhibition of flow of free fatty acids (FFA) from adipose tissue which provides
acetyl CoA molecules essential for cholesterol and triacylglycerols synthesis.
3. Formation of ADP-ribose: NAD+ is a source of ADP-ribose: It is important for:
a) ADP-ribosylation of protein.
b) Poly ADP ribosylation of nucleoproteins involved in DNA repair mechanism.
• Deficiency: pellagra
- Deficiency of niacin causes pellagra, a disease affects the skin, GIT and CNS.
- Manifestation of pellagra:
- Pellagra is called a disease of (4 Ds): diarrhea, dermatitis, dementia and if not
treated death.
- Causes:
a) Deficiency of niacin, tryptophan or vitamin B6.
b) Corn is deficient in both niacin and tryptophan. Thus people who depend on corn
as a major source of protein as some farmers develop pellagra.
c) Hartnup’s disease: It is a hereditary disease in which here is defect in tryptophan
absorption form intestine and tryptophan reabsorption by renal tubules →
Pellagra.
d) Argentaffinoma (malignant carcinoid syndrome): In which large quantities of
tryptophan is converted to serotonin. This occurs on the expense of niacin
synthesis → pellagra.
e) Isoniazid: it is a drug that is used in treatment of tuberculosis. Isoniazid binds
with B6 → Excretion by kidney → pellagra.
• Requirements: Niacin 20 mg / day.
• Hypervitaminosis of niacin:
- More than 500 mg/day may cause liver damage.
Pyridoxine (vitamin B6)
• Sources: wheat, egg yolk, corn, liver and meat.
• Structure:
1. Vitamin B6 includes a group of Vitamers derived from pyridine ring.
2. These are pyridoxine, pyridoxal and pyridoxamine.
- They differ in the, nature of functional group attached to the ring.
- All 3 compounds can act as precursors of the biologically active co-enzyme
Pyridoxal phosphate (PLP).

DR. Mahmoud Ettaweel 01004486188 188

• Functions:
- In the body, pyridoxine is converted to pyridoxal phosphate, which acts as a
coenzyme for a large number of enzymes:
A. In protein metabolism:
It acts as a coenzyme for amino acids metabolism in the following reactions:
1) Transamination e.g.
Glutamate + Oxaloacetate ↔ α-Ketoglutarate + Aspartate
2) Trans-sulfuration e.g.
Methionine → Homocysteine (+ serine) → Cysteine + Homoserine.
3) Deamination e.g.
Serine → Pyruvate +NH3
4) Decarboxylation e.g.
Glutamate → GABA + CO2
5) Heme synthesis e.g.
Glycine + Succinyl CoA → δ Aminolevulinic acid → Heme.
6) Pyridoxal phosphate acts as a coenzyme in conversion of tryptophan into
vitamin B3 (niacin).
7) Sphingosine synthesis: Serine + Palmitate
8) It takes a role in amino acids absorption from the intestine.
B. In carbohydrate metabolism: Pyridoxal phosphate acts as a coenzyme of glycogen
Phosphorylase → Glycogen breakdown into glucose (glycogenolysis).
C. In lipids metabolism: Pyridoxal phosphate is important in steroid hormone action,
where it removes the hormone- receptor complex from DNA binding, terminating
the action of hormone.

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• Deficiency:
1. Pellagra may result, because pyridoxal phosphate is needed for the conversion of
tryptophan into vitamin B3 (niacin).
2. Convulsions in young infants due to deficient formation of GABA (inhibitory
transmitter in brain).
3. Anemia (microcytic and hypochromic) due to deficient formation of heme and
hemoglobin.
4. Disturbance in amino acids metabolism. This leads to growth retardation and may
be mental retardation.
5. Cancer breast, uterus and prostate: due to defective action of B6 on steroid DNA
binding.
6. Homocystenuria: It is due to inability to convert Methionine to cysteine.
• Hypervitaminosis of B6:
- Intake of more than 200 mg/day B6 may cause neurological damage.
• Requirements: 2 mg / day.
Pantothenic acid
• Sources:
- Animal tissue as meat, liver, kidney.
- Legumes.
• Structure:
- Pantothenic acid is formed of pantoic acid (α and γ dihydroxy β dimethyl butyric
acid) connected to β-alanine.
• Functions:
1. Coenzyme A (CoASH):
a) Structure: is formed of phosphopantotheine (= phosphate + pantothenic acid +
Thioethylamine) attached to biphosphoadenosine.
b) Function:
- Coenzyme A acts in the transfer of acyl groups e.g. acetyl CoA, Succinyl CoA,
malonyl CoA and other carboxylic acids.
1) Acetyl CoA: It is an important intermediate in metabolism of carbohydrate,
lipids and protein metabolism.
2) Succinyl CoA: used in heme synthesis and other reactions.
3) Malonyl CoA: is used in fatty acid synthesis.

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 2. Acyl carrier protein (ACP):
a) Structure: ACP is formed of: Pantothenic acid connected to phosphate and
protein in one side and Thioethylamine in the other side.
b) Functions: ACP is a component of fatty acid synthase enzyme required for fatty
acid synthesis.
• Deficiency: Deficiency of pantothenic acid causes no effect in human.
• Requirements: 5 - 10 mg / day.
Biotin
• Sources:
1. The intestinal bacteria synthesize most of the
human requirements of biotin.
2. Egg yolk, animal tissues, tomatoes and yeast are
excellent sources.
• Structure:
- Biotin consists of thiophen ring connected to urea
with Valeric acid as side chain
- Biotin acts as CO2 carrier. It attaches to
carboxylase enzyme (through the ε amino group
of lysine residues to form biocytin a reaction
catalyzed by holocarboxylase synthetase enzyme.
- Deficiency of such enzyme may lead to deficiency
manifestation of biotin.
- CO2 is attached to N of biotin to form CO2 biotin
enzyme complex.
• The CO2 group→is CO
Functions: then transferred to the substrate
2 fixation
for carboxylation.
A. Biotin is a CO2 carrier. It acts as coenzyme for carboxylase enzymes that catalyze
carboxylation reactions.
- Example of important carboxylation reactions are:
1. Carboxylation of acetyl CoA to malonyl CoA:
Is important reaction in fatty acid synthesis.
2. Carboxylation of pyruvate to oxaloacetate:
Is important reaction in Gluconeogenesis.
3. Carboxylation of Propionyl CoA to give Succinyl CoA.
B. Regulation of cell cycle: Biotin also has a role in regulation of cell cycle.
• Deficiency:
1. Deficiency of biotin does not occur in man because:
- The intestinal bacteria supply all the human needs.
- Biotin is widely distributed in food.
2. Biotin deficiency may result from:
a) Ingestion avidin: it is a glycoprotein present in uncooked egg white. It tightly
binds biotin and prevents its absorption from the intestine.

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 b) Deficiency of holocarboxylase synthetase enzyme in children. This enzyme is
responsible for the attachment of biotin to carboxylase enzyme.
3. The manifestations biotin deficiency include:
Muscle pain, dermatitis, Glossitis, loss of appetite and nausea.

2. The requirements increase during late pregnancy and lactation.

Choline
- Choline is sometimes not regarded as a vitamin because:
1. It is needed in a relatively big amount.
2. It can be formed in the body from serine.
3. It enters in structure of tissues.
• Physiological function:
1. It enters in the formation of lecithin and Sphingomyelin.
2. It has a lipotropic action. i.e. it prevents fatty liver.
3. It enters in the formation of acetylcholine.
4. Oxidation of Choline produces betaine. Betaine functions as a methyl donor in
Transmethylation reactions.
Inositol
• Structure: It is sugar alcohol derived from glucose.
• Physiological functions:
1. It enters in the structure of Phosphatidyl Inositol, which act as lipotropic factor.
2. Inositol triphosphate (IP) acts as a second hormone messenger (see mode of action
of hormones).
- Note: Inositol can combine with 6 molecules of phosphoric acid to form Phytic acid.
Phytic acid combines with Ca2+ ions to form Ca2+ phytate which is insoluble in water.
So, the presence of phytic acid in food decreases Ca2+ absorption.
Lipoic acid
• Structure:
It is 6-8 dithio-ocatnic acid (8C)
• Physiological functions:
- It acts as coenzyme in oxidative decarboxylation of α-Keto acids e.g. pyruvic acid

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1- Harper's 30th edition

2- Lippincott

3- First Aid 2018

4- Kaplan Biochemistry

5- BRS biochemistry