LIPIDS

By Girum Getachew
RVU
 Lipids
• Lipids comprise very heterogeneous group of
compounds which are insoluble in water
• But soluble in non-polar organic solvents such
as:
– Benzene,
– Chloroform, and
– Ether.
• They are present in all living organisms.
• The group includes:
• Fats,
• Oils,
• Waxes and
• Related compounds.
 General Functions of Lipids

• 1.They are efficient energy sources.

• 2.Serve as thermal insulators.
• 3.They are structural components of the cell
membrane.
• 4.Serve as precursors for hormones (steroid
hormones).
• 5.They also dissolve the vitamins, which are
fat-soluble and assist their digestion.
• (vitamins A, D, E and K)
 Classification:
• Classification based on lipid composition:
• I. Simple lipids:
– Esters of fatty acids with different alcohols.
• Fats and oils:
– These are esters of fatty acids with glycerol.
• Waxes:
– Esters of fatty acids with high molecular
weight monohydric alcohols
• II. Complex lipids:
• Esters of fatty acids and alcohols together with
some other head groups.
• A. Phospholipids:
• Esters of the above type containing
phosphoric acid residue.
• a) Glycerophospholipids:
– The alcohol is glycerol
• b) Sphingophospholipids:
– The alcohol is sphingosine.
• B. Glycolipids:
• Lipids containing fatty acid, sphingosine and
carbohydrate residues.
• C. Others:
• Include sulfolipids, amino lipids and
lipoproteins, which are modified forms of
lipids.
• III. Derived lipids:
– include the hydrolytic products of the
simple and complex lipids.
– Eg. Fatty acids, cholesterol etc.
• The simplest naturally occurring lipids are
triacylglycerols
• Formed by esterification of fatty acids with
glycerol.
• Biological membranes are made up of
phospholipids, glycolipids and proteoglycans.
 FATTY ACIDS
• The fatty acids are the basic units of lipid
molecules.
• Over 200 fatty acids have been isolated from
various lipids.
• They differ among themselves in:
– hydrocarbon chain length,
– number and position of double bonds
– the nature of substituents
– such as oxy-, keto-, epoxy groups and cyclic
structure.
• Depending on the absence, or presence
of double bonds, they are classified into
two :
• 1. Saturated and
• 2. Unsaturated fatty acids.
 1. Saturated Fatty Acids
• Saturated fatty acids, do not contain double
bonds.
• The hydrocarbon chain may contain 12 to 18
carbon atoms.
• eg. palmitic and stearic acids.
• CH3 (CH2)14 COOH - Palmitic acid (C-16)
• CH3(CH2)16 COOH - Stearic acid (C-18).
 2.Unsaturated Fatty Acids
• Unsaturated fatty acids are classified into
different types depending on the
number of double bonds present in the
hydrocarbon chain.
• These fatty acids are mainly found in
plant lipids.
 Structure of a Fatty Acid
• Fatty acids are derivatives of aliphatic
hydrocarbon chain that contains a carboxylic
acid group.
• Made of long chain organic acids having one
polar carboxyl group (head) and a non-polar
hydrocarbon chain (tail).
• The latter makes them water insoluble.
• They are not found free in nature but found
as esterified forms.
• Most naturally occurring fatty acids have got
even number of carbons.
• They may be saturated or unsaturated, with
one or more double bonds.
• Mostly the double bond occurs at the 9th
carbon as we count from the carboxyl group
end.
• There are two systems of numbering
the carbon atoms in a fatty acid
• 1. Numbering starts from carboxyl carbon.
• The last carbon is the "n" carbon
• 2. The second carbon is the "α“ and the third
the "β" Carbon.
• The last carbon atom is ω omega.
• Eg:CH3 (CH2)7 CH2CH2 (CH2)7 COOH
• Stearic acid (saturated fatty acid)
• Eg: CH3 (CH2)7 CH=CH (CH2)7 COOH
• Oleic acid (Unsaturated fatty acid)
• Fatty acids can be represented as:
• C18:1, Δ9
• The delta indicates the position of the
double bond and
• The next number shows the number of
carbon atoms and
• The last number indicates the number of
double bonds.
• In a different way the position of the
double bond(s) can be indicated as
without the delta:
• 18:1(9)
• C18 indicates 18 carbons,
• 1 indicates the number of double bonds,
• 9 indicates the position of double bond
between 9th and 10th carbon atoms.
• Double bonds in naturally occuring fatty
acids are in the cis- configuration
• Saturated fatty acids of C12 to C24 are
solids at body temperature
• But the unsaturated once are liquids.
 Essential Fatty Acids

• Fatty acids required in the diet are called

essential fatty acids (EFA).
• They are not synthesized by the body and are
mainly polyunsaturated fatty acids (PUFA).
• Linoleic acid, Linolenic acid, Arachidonic acid
• Arachidonic acid is semi essential fatty acid
because it can be synthesized from two
essential fatty acids.
• Essential Fatty Acids
• Eg:
• 18 Linoleic acid 18: 2; 9 (12)
• 18 Linolenic acid 18: 3; 9 (12, 15)
• 20 Arachidonic acid 20: 4; (5, 8, 11, 14)
• Functions of essential fatty acids
• They are required for
– Membrane structure and function,
– Transport of cholesterol,
– Formation of lipoproteins and
– Prevention of fatty liver.
• Deficiency of essential fatty acids
• The deficiency of essential fatty acid
results in phrynoderma or toad skin-
scaly dermatitis (ichthyosis),
• As well as visual and neurologic
abnormalities.
• Essential fatty acid deficiency is rare.
 Biosynthesis of fatty acids
• 1. Biosynthesis of fatty acids occurs in all
organisms and in mammals
• It occurs mainly in
• Adipose tissue,
• Mammary glands, and
• Liver.
• 2. Fatty acid synthesis takes place in the
cytosol in two steps.
• a) Formation of medium chain fatty
acid of chain length 16 carbon atoms.
• b) Lengthening of this carbon chain in
microsomes for larger fatty acids.
• 3. Acetyl CoA serves as a source of carbon
atoms for saturated as well as unsaturated fatty
acids.
• Acetyl CoA can be formed from excessive
dietary glucose and glucogenic amino acids
(amino acids which can be converted to
glucose).
• Carbohydrates and aminoacids in the presence
of oxygen is converted to pyruvate which inturn
can be converted to acetyl CoA..
• The synthesis of fatty acid from acetyl
CoA takes place with aid of a multi-
enzyme complex termed as fatty acid
synthetase complex.
• Palmitic acid is the major product of the
fatty acids synthetase complex mediated
reaction and hence it is also called as
palmitate synthetase.
• It is a dimer with two identical subunits
namely subunit-1 and subunit-2
arranged in a head to tail fashion.
• Each monomer of this enzyme complex
contains seven enzymes; of these, each
is assigned a definite function.
• Migration of Acetyl CoA for the bio
synthesis of Fatty acids
• Formation of acetyl CoA from pyruvate
takes place in mitochondria.
• Mitochondrial membrane is
impermeable to acetyl CoA.
• Migration of acetyl CoA from the
mitochondria to the cytoplasm is facilitated by
the condensation of the acetyl CoA with
oxaloacetate to form citrate which is
permeable to mitochondrial membrane.
• In the cytoplasm, citrate readily decomposed
back to acetyl CoA and oxaloacetate in the
presence of ATP and co-enzyme A by the
action of an enzyme called ATP – Citrate lyase.
• Conversion of Acetyl CoA to Malonyl CoA
• The acetyl - CoA is carboxylated in the
cytoplasm in the presence of acetyl CoA
carboxylase, a vitamin Biotin containing
enzyme, which helps in carbondioxide
fixation.
• Acetyl CoA carboxylase is the regulatory
enzyme in the fatty acid biosynthesis.
Conversion of malonyl CoA to palmitic acid
• The malonyl CoA is converted to palmitic
acid by several steps and each of these
steps are catalysed by different enzymes
of fatty acid synthetase complex.
• Acetyl CoA and malonyl CoA condenses
to form butyryl-ACP with the formation
of intermediates.
• This cycle repeats itself six times and in
each cycle two carbon atoms (malonyl
CoA) is added to butyryl ACP,
• Ultimately resulting in the formation of
palmitoyl CoA, a 16 carbon molecule.
 Oxidation of Fatty Acids
• Fatty acids are the immediate source for
oxidation of fats in various tissues:
– Liver, Adipose Tissue, Muscles,
– Heart, Kidney, Brain, Lungs and Testes.
• Fatty acids are oxidised to CO2 and water
with the liberation of large amount of
energy.
• Oxidation is brought about in the
mitochondria
• because all the enzymes required for
oxidation are present in the
mitochondria.
• Oxidation of fatty acids is of three types,
• Based on the position of the carbon
atom which gets oxidised (α,β,γ).
Mechanism of diabetic ketoacidosis seen in type 1 diabetes.
 TRIACYLGLYCEROLS
• These are esters of fatty acids with the
alcohol glycerol,
• Which are storage forms of lipids (depot
lipids).
• Triacylglycerols or also called as
triacylglycerides, exist as simple or mixed
types
• Depending on the type of fatty acids that form
esters with the glycerol.
• Both saturated and/or unsaturated fatty acids
can form the ester linkage with the backbone
alcohol.
• Eg. Tripalmitate,Triolein.
Structure of Triacylglycerol.R1, R2 and R3 are fatty acids.
• Tristearin is a chief component of beaf lipid
• Butter has short chain fatty acids.
• Unsaturated fatty acids are sensitive to air and
oxidized to give rancid smell.
• Triacylglycerols are mainly found in special
cells called adipocytes (fat cells), of the
mamary gland, abdomen and under skin of
animals.
• They produce twice as much energy as that of
carbohydrates per gram
• The second largest membrane lipids are
sphingolipids,
• which contain two non-polar and one polar
head groups.
• Their alcohol is the amino alcohol sphingosine.
• Sphingolipids have subclasses: sphingomyelins,
cerebrosides and gangliosides.
• Out of these only sphingomyelin contains
phosphorus.
Glycerophospholipids
 CHOLESTEROL

• Cholesterol is a very hydrophobic compound.

It consists of four fused hydrocarbon rings (A-
D) called the “steroid nucleus”), and
• It has an eight-carbon, branched hydrocarbon
chain attached to carbon 17 of the D ring.
• Ring A has a hydroxyl group at carbon 3, and
ring B has a double bond between carbon 5
and carbon 6.
• Cholesterol is the major sterol in animal
tissues.
• Compounds containing 27 carbon cyclo-
pentano-perhydro-phenanthrene
• Structures with four rings labeled A B C D.
• Steroids are complex fat-soluble molecules,
which are present in the plasma lipoproteins
and outer cell membrane.
• Cholesterol is one of the important non fatty
acid lipid that is grouped with steroids.
• Sterols
• Steroids with eight to ten carbon atoms in the
side chain at carbon 17 and a hydroxyl group
at carbon 3 are classified as sterols.
• Cholesteryl esters
• Most plasma cholesterol is in an esterified
form (with a fatty acid attached at carbon 3,
Structure of Cholesterol
• Cholesterol is important in many ways:
• For the synthesis of bile salts that are
important in lipid digestion and absorption.
• For the synthesis of steroid hormones that
are biologically important like the sex
hormones estrogen and progesterone.
• For the synthesis of vitamin D3
• As a structural material in biological
membranes.
• As a component of lipoproteins as transport
forms of lipid based energy.
 Lipoproteins
• Lipids, such as cholesterol and triglycerides,
are insoluble in plasma
• Circulating lipid is carried in lipoproteins that
transport the lipid to various tissues for:
– Energy utilization,
– Lipid deposition,
– Steroid hormone production, and
– Bile acid formation.
• The lipoprotein consists of:
– Esterified and unesterified cholesterol,
– Triglycerides, and
– Phospholipids, and
– Protein.
• The protein components of the lipoprotein are
known as apolipoproteins (apo) or apoproteins.
• The different apolipoproteins serve as cofactors
for enzymes and ligands for receptors.
 CLASSIFICATION —
• There are five major lipoproteins, each of
which has a different function.
– Chylomicrons
– Very low density lipoprotein(VLDL)
– Intermediate density lipoprotein(IDL)
– Low density lipoprotein (LDL)
– High density lipoprotein(HDL)
• Chylomicrons are very large particles that
carry dietary lipid.
• They are associated with a variety of
apolipoproteins, including A-I, A-II, A-IV, B-48,
C-I, C-II, C-III, and E.
• Very low density lipoprotein (VLDL) carries
endogenous triglycerides and to a lesser
degree cholesterol.
• The major apolipoproteins associated with
VLDL are B-100, C-I, C-II, C-III, and E.
• Intermediate density lipoprotein (IDL) carries
cholesterol esters and triglycerides.
• It is associated with apolipoproteins B-100, C-III,
and E.
• Low density lipoprotein (LDL) carries cholesterol
esters and is associated with apolipoproteins B-
100 and C-III.
• High density lipoprotein (HDL) also carries
cholesterol esters.
• It is associated with apolipoproteins A-I, A-II, C-I,
C-II, C-III, D, and E.
 Digestion and Absorption of Lipids

• Diet contains triglycerides, cholesterol and its

ester, phospholipids, fatty acids etc.
• Mouth and gastric juice has got lipase.
• It can hydrolyse fats without emulsification
with bile salts.
• Milk fat and butter fat is digested by the
enzyme.
• Major part of fats are digested by pancreatic
lipase.
• It acts on emulsified lipids only.
• The products are monoglyceride and 2 fatty
acids.
• Monoglyceride is further hydrolyzed by another
lipase.
• Thus 3 fatty acids and one glycerol molecule is
produced from the digestion of dietary
triglyceride.
Action of lipase on TAG
 Functions of Bile Salts
• They lower surface tension ,emulsify fats ,a pre
requisite for the action of pancreatic lipase
• They activate Lipase.
• They shift the pH from 9 to 6
• They form micelles with fatty acid,a
mono,di,triglyceride and help in absorption
• Promote absorption of fat soluble vitamins
• Bile salts keep cholesterol in soluble form in
gall bladder.
• They regulate the breakdown of cholesterol
 Cholelitiasis (Gall stones):

• Absence of bile salts precipitate cholesterol as gall stones.

• Solublity of cholesterol depends on the ratio of
phospholipids, bile salts to cholesterol.
• Due to infections bile acids are destroyed which leads to
decreases solubility of cholesterol.
• Decrease of bile salts can be due to:
• A. Failure in enterohepatic circulation
• B. Cirrhosis of Liver
• C. Disease of ileum.
• Gall stone formed
• Treatment -Surgery
A cholesterol gallstone before and after in-vitro laser lithotripsy
 Hypercholesterolemia :

• Normal cholesterol level is 150-250mg% in

blood.
• High concentration leads to hyper
cholesterolemia.
• Excess cholesterol gets deposited under the
skin, tendons as Xanthomas.
 Atherosclerosis:

• Deposition of lipids in the connective tissues of

intima of arteries is called atherosclerosis.
• It causes obstruction to blood flow, leading
coronary heart disease, stroke, myocardial
infarction etc.
• The process is initiated when there is injury to
endothelial cells of blood vessels.
• A number of factors are responsible for injury .
• The condition is compounded by hyper lipidemia.
 Fatty Liver:

• Excess accumulation triglycerides in liver causes

fatty liver, Liver cirossis and failure of liver
function.
• Causes are:
• Elivated levels of free fatty acid in blood
• Deficiency of lipotropic factors, which help in the
mobilization of fat from liver
• Failure in the secretion of lipoproteins from liver
• Chronic alcoholism
• Prolonged treatment with antibiotics
Thank You!