CARBOHYDRATES

- Carbon, Hydrogen & Nitrogen OPTICAL ACTIVITY

- They are biomolecules found abundantly in living - Caused by the presence of asymmetric carbon
organisms. atom.
- Most abundant macromolecules in nature - According to the direction of rotation, molecules
- Contain more than one hydroxyl group are referred to as dextrorotatory (d) if they rotate
(polyhydric) in addition to aldehyde or ketone in the right or clockwise direction or levorotatory
group. (l) if they rotate in the left or counterclockwise
- Form into polyhydroxy aldoses or polyhydroxy direction when a plane-polarized light beam is
ketoses. passed through a solution of carbohydrates.
- Provide energy - D-glucose= dextrorotatory
- Act as storage molecule of energy - D-fructose= levorotatory
- Serve as a cell membrane component and - If equal amount of D & L isomers are present, the
mediate some forms of communication between resulting mixture has no optical activity, since the
cells. activity of each isomer cancel one another.
- Main source of energy in the body (racemic/DL mixture)
EPIMERS
CLASSIFICATION OF CARBOHYDRATES - Sugars that differ from one another only in the
I. MONOSACCHARIDE (mono=one) arrangement of a single carbon atom (around
- Simple sugars one atom) are referred to as epimers for one
- Consists of a single polyhydroxy aldehyde or another. Ex: glucose & mannose
ketone units ANOMERS
- 6-carbon sugar like D-glucose and fructose - Diastereomers (having different physical
(most abundant monosaccharides) properties)
- Has a backbone which is un-branched, single ➢ Alpha anomer: -OH group is down (Haworth)
bonded carbon chain. One of the carbon ➢ Beta anomer: -OH group is up (Haworth)
CYCLIZATION OF MONOSACCHARIDES
atoms is double bonded to an oxygen atom
- Monosaccharides with 5 or more carbon atoms
to form carbonyl group. Each of the other
in the backbone usually occur in solution as
carbon atoms has hydroxyl group. cyclic/ring structure.
- Aldehyde can react with alcohol to form a
hemiacetal or acetal.
➢ The C-1 aldehyde in the open-chain form of
glucose reacts with the -5th carbon atom
containing hydroxyl group to form an
intramolecular hemiacetal. The resulting 6
membered ring is called pyranose (similarly
to organic molecule pyran)
➢ The C-2 keto group in the open chain form of
Open chain D-glucose fructose can react with the 5th atom carbon
PHYSICAL PROPERTIES OF MONOSACCARIDE atom containing hydroxyl group to form an
- Colorless, crystalline compounds, readily soluble intermolecular hemiketal. The 5 membered
in water. ring is called furanose (similarity to organic
- Their solutions are optically active and exhibit molecule furan)
the phenomenon of mutarotation. - 2 different forms of glucose are formed when the
ASYMMETRIC CENTER AND STEREOISOMERISM OH group extend to right – α-D-Glucose and
when it extends to left- β-D-Glucose (anomers)
When the -OH group on this carbon is on the right, the
sugar is a member of the D-series, when it is on the left,
it is a member of L-series.
II. OLIGOSACCHARIDES (2-10 monosaccharide unit) ➔ Amylopectin-(1,4)
- GLYCOPROTEINS (Mucoproteins)- proteins to o Consists of long branched glucose
which oligosaccharides are covalently attached. residue with high molecular weight
The length of the glycoprotein carbohydrate o Like amylose, the inner part of the
chain is short (usually 2-10 / more sugar residue) glucose units in amylopectin are linked
- DISACCHARIDES by -(1,4) glycosidic links, whereas the
➢ Most abundant oligosaccharides found in branch points are connected by -(1,6)
nature. linkages. Every 20-30 (1-4) linkage, this
➢ Formed when 2 monosaccharides are branch points repeat.
covalently bonded together by glycosidic ➢ Glycogen
linkage (formed when the hydroxyl group on • Main storage polysaccharide of animal
one pf the sugar reacts with anomeric cells
carbon on the 2nd sugar. • Present in the liver and in skeletal muscle
- MALTOSE • Like amylopectin, branched
➢ Major degradative product of starch polysaccharide of D-glucose units in α-
➢ Hydrolyzed 2 molecules of D-glucose residue (1,4) linkage but is highly branched.
between OH at the 1st carbon atom of the 1st • The branch are formed by α-(1,6)
glucose and OH at the 4th carbon atom at the glycosidic linkage that occurs after every 8-
2nd glucose by the intestinal enzyme maltase 12 residues.
forming a α-(1,4) glycosidic bond. ➢ Cellulose
- LACTOSE • Most abundant structural polysaccharide
➢ Disaccharide of β-D-galactose and β-D- in plants.
glucose which are linked by β-(1,4) glycosidic • Fibrous, tough, water insoluble
linkage. • In a linear unbranched
➢ Act as a reducing substance since it has homopolysaccharide of 10000 or more D-
carbonyl group on the glucose. glucose units connected by β-(1,4)
➢ Found in milk of mammals. glycosidic bonds.
- SUCROSE • Cannot used by humans because they lack
➢ Disaccharide of α-D-glucose and β-D- enzymes to hydrolyze the β-(1,4) linkage.
fructose. ➢ Dextrin
➢ From sugar cane & also present in various • Highly branched homopolymers of glucose
fruits units with α-(1,6), α-(1,4) and α-(1,3)
➢ Contains no free anomeric carbon atom. linkages
➢ Non-reducing sugar
• Since the do not easily go out of vascular
III. POLYSACCHARIDES (>10 monosaccharide units)
compartment they are used for
- Found in nature occur in the form of high
intravenous infusion as plasma volume
molecular polymers.
expander in the treatment of hypovolemic
- HOMOPOLYSACCHARIDE
shock
➢ Contains only one type of monosaccharide
building blocks.
- HETEROPOLYSACCHARIDES
➢ Ex: starch, glycogen, cellulose & dextrin
➢ Containing more than one type of sugar
➢ Starch
residues
• One of the most important storage
• Glycosaminoglycans
polysaccharide in plant cells.
(GAGS/mucopolysaccharides)
• Especially abundant in tubers (potatoes ➔ Long and usually unbranched
& cereals) ➔ Composed of a repeating disaccharide
➔ Amylose unit.
o Unbranched with 250-300 D-glucose ➔ Negatively.charged
units linked by α-(1,4) heteropolysaccharides chains.
 • Function of GAGS III. DIGESTION IN DUODENUM (large intestine)
➔ Have special ability to bind large - Food reaches the duodenum from stomach where
amounts of water, thereby producing it meets the pancreatic juice- (contains a
the gel-like matrix that forms the basis carbohydrate-splitting enzyme pancreatic amylase)
of the body’s ground substance. - Action of pancreatic amylase
➔ Since they are negatively charged, ➢ Also an α-Amylase, optimum pH 7.1 & also
they can attract and tightly bind requires Cl- ion for activity.
cations and also take up Na+ and K+ ➢ Enzyme hydrolyzes α-(1,4) glycosidic linkage
➔ Stabilize and support cellular and situated well inside polysaccharide molecule.
fibrous components of tissue while IV. DIGESTION IN SMALL INTESTINE
helping maintain the water and salt - Action of intestinal juice
balance of body. ➢ Pancreatic amylase
➔ It’s essential components of the extra • It hydrolyzes terminal α-(1,4), glycosidic
cellular matrix play an important role linkage in polysaccharides and
in mediating cell-cell interaction. oligosaccharide molecules liberating free
• Ground substance glucose molecules.
➔ Part of connective tissue, which is a ➢ Lactase
gel like substance containing water, • A β-glycosidase, its pH range is 5.4-6.0.
salt, proteins and polysaccharide. • Lactose is hydrolyzed to glucose and
➔ Ex: synovial fluid (serve as a lubricant galactose.
in joints and tendon sheaths) - Lactose intolerance – adults cannot digest sugar
• Heparin and it remains in the intestines and gets fermented
➔ Contains a repeating unit of D- by the bacteria. Such patients suffer from watery
glucuronic and D-gluconsamine, with diarrhea, abdominal intestinal flow, and chronic
sulfate groups on some of the pain (advised to avoid foods containing milk).
hydroxyl and aminx-group. ➢ Maltase
➔ An essential anticoagulant that • The enzyme hydrolyzes the α-(1,4)
inhibits the conversion of glycosidic linkage between glucose units in
prothrombin to thrombin prevents maltose molecule liberating two glucose
blood from clotting. An enzyme called molecules pH rage= 5.8-6.2
thrombin affects the conversion of
plasma fibrinogen to fibrin.
➔ Found in mast cells in lung, liver skin ➢ Sucrase
and intestinal mucosa. • pH range = 5-7
• Proteoglycans
➔ GAGS attached to a protein molecule

METABOLISM OF CARBOHYDRATES
V. ABSORPTION OF CARBOHYDRATES
I. DIGESTION IN MOUTH
- Products of dietary carbohydrate digestion are
- Saliva contains a carbohydrate splitting enzyme
almost entirely absorbed from the small intestine.
called salivary amylase (ptyalin)
- Absorption from proximal jejunum is 3x > distal
- Action of ptyalin
ileum. Some disaccharides that escape digestion,
may enter the cells of the intestinal lumen by
“pinocytosis” & are hydrolyzed with these cells.
- No carbohydrates higher that monosaccharide can
II. DIGESTION IN STOMACH be absorbed directly into bloodstream.
- No carbohydrate splitting enzyme in gastric juice.
- Hydrochloric acid may hydrolyze dietary sucrose to
equal amounts of glucose and fructose.
VI. MECHANISM OF ABSORPTION ➢ REACTION OF GLYCOLYTIC PATHWAY
- Simple diffusion (simple passive diffusion) • STAGE 1 (preparatory stage)
➢ Dependent on sugar concentration gradients ➔ Uptake of glucose by cells and its
between the intestine lumen. phosphorylation – Glucose is freely
➢ Mucosal cells & blood plasma permeable to liver cell. In intestinal
➢ All monosaccharides are probably absorbed. mucosa and kidney tubules, glucose is
- Active transport mechanism taken up by active transport. Then
➢ Glucose and galactose are absorbed very phosphorylated to form glucose-6-
rapidly (they are absorbed actively and phosphate. The reaction is catalyzed
requires energy) by the specific enzyme glucokinase in
➢ Fructose absorption is also rapid but not so liver cells by nonspecific hexokinase in
much as compared to glucose and galactose liver and extrahepatic tissues.
but it is faster than pentose. ➔ Conversion of G-6-phosphate to
• Fructose is not absorbed by simple diffusion fructose 6-phosphate
alone and some mechanism facilitates its
transport (facilitated transport)
VII. GLYCOLYSIS (Embden Meyerhoff Pathway)
- Described by Embden, Meyerhoff, & Parnas
- Oxidation of glucose or glycogen to pyruvate & lactate. ➔ Conversion of fructose 6 phosphate to
- Occurs virtually in all tissues. fructose1, 6 biphosphate
- Erythrocytes and nervous tissues derive its energy
mainly form glycolysis. This pathway is unique in
the sense that It can utilize O2 if available (aerobic)
& it can function in absence of O2 also (anaerobic)
- Aerobic phase o Reaction one is irreversible.
➢ conversation of glucose to pyruvate o One ATP is utilized for
➢ produce ATP phosphorylation of glucose at
➢ Oxidation is carried out by dehydrogenation position 6.
and reducing equivalent id transferred to NAD. o Phosphofructokinase I is the key
NADH+H+ in the presence of O2 is oxidized in enzyme in glycolysis that regulate
electron-transport chain producing ATP. the pathway.
- Anaerobic phase o Phosphofructokinase II
➢ Conversation of glucose to lactate
➢ NADH cannot be oxidized, so no ATP.
➢ NADH is oxidized to NAD+ by conversation of
pyruvate to lactate w/out producing ATP.
➢ Limits the amount of energy per molecule of
glucose oxidized. To provide a given amount  Energetics – This stage glucose
ofenergy3, more glucose must undergo oxidation does not yield any
glycolysis under anaerobic as compared to useful energy rather there is
aerobic. expenditure of 2ATP
A. Enzyme molecules for 2
➢ Enzyme involved in glycolysis is present in phosphorylation (-2ATP).
cytoplasm.
➢ Significance of pathway (provision of energy)
• Important in skeletal muscle as glycolysis
provides ATP even in absence of O2
muscles can survive under anaerobic
condition.
• STAGE II • STAGE IV (recovery of PO4 group from 3-
➔ Fructose 1, 6-bisphosphate is split by phosphoglycerate)
the enzyme aldolase into 2 molecules ➔ Conversation of 3-phosphoglycerate
of triosephosphate, an aldotriose, of 2-phosphoglycerate
glyceraldehyde 3 phosphate and a o 3- phosphoglycerate formed by
ketotriose, dihydroxyl acetone the above reaction is converted
phosphate. to 2-phosphoglycerate, catalyzed
o The reaction is reversible. by the enzyme phosphoglycerate
o There is neither expenditure of mutase.
energy nor formation of ATP. ➔ Conversation of 2-phosphoglycerate to
o Aldolases are tetramers phosphoenol pyruvate
(4subunits) o The reaction is catalyzed by the
o Aldolase B – found in liver & enzyme enolase the enzyme
kidney. requires the presence of either
o The fructose -6-p exists in the cells Mg++/Mn++
in “furanose” form but they react o The reaction involves dehydration
with isomerase, & redistribution of energy w/in the
phosphofructokinase-1 and molecule rising PO4 in position 2 to
aldolase in the open-chain a “high-energy state”.
configuration. ➔ Conversation of phosphoenol to
o Both triose phosphates are phosphoenol pyruvate
interconvertable.

• STAGE III (energy yielding reaction

➔ Aldehyde group is oxidized to an acid
are accompanied by liberation of large ➢ SIGNIFICANCE OF LACTATE INFORMATION
amounts of potentially useful energy. ➔ Under anaerobic conditions NADH via re
o Oxidation of glyceraldehyde oxidized via lactate formation. This allows
3phosphate to 1, 3bisphosphate glycolysis to proceed in the absence of oxygen.
 Energetics This process generates enough NAD for
1. In 1st reaction, NADH produced another cycle of glycolysis.
will be oxidized in the electron B. CLINICAL IMPORTANCE
transport chain to produce 3ATP
in presence of O2. Since 2 - Tissues that function under hypoxic (lack of
molecules of triose phosphate oxygen gas) conditions will produce lactic acid
are formed per molecule of from glucose oxidation. Produce local acidosis. If
glucose oxidized, 2NADH will lactate production is more it can produce
produce 6ATP. metabolic acidosis (magiging acidic ang blood)
2. The 2nd reaction will produce ATP. - Whether O2 is present or not, glycolysis in
2 molecules of substrate will erythrocyte always terminated in to pyruvate
produce ATP. Net gain at this and lactate.
stage per molecule of glucose
oxidized = +8ATP.
- ENTRY OF FRUCTOSE INTO GLYCOLYSIS ➔ Conversion of glucose 6 phosphate to
glucose occurs in the liver, kidney and
intestine by the action of glucose 6
phosphate. This does not occur in the
skeletal muscle as it lacks the enzyme.
• Removal of branches
➔ A debranching enzyme also called
glucan transferase which contains two
activities, Glucantransferase &
Glucosidase. The glucose in α-(1,6)
linkage at the branch is removed by the
action of glucosidase as free glucose.
- GALACTOSE (glucose in milk) • Lysosomal degradation of glycogen
➢ Galactokinase converts galactose to galactose ➔ A small amount of glycogen is
1-P. it reacts with UDP-glucose to form UDP- continuously degraded by the
galactose and glucose-1-P. The enzyme is lysosomal enzyme α-(1,4) glycosidase
galactose 1-P uridylyl transferase. UDP- (acid maltase). A deficiency of this
galactose can be epimerized to UDP- glucose enzyme causes accumulation of
by 4-epimers. Glycogenesis also requires UDP- glycogen in vacuoles in the cytosol,
glucose. UDP-galactose can be condensed with resulting in a very serious glycogen
glucose to form lactose. storage disease called type II (pomp’s
- GALACTOSEMIA disease)
➢ It is an inherited disorder that the defect may ➢ Synthesis of Glycogen (glycogenesis)
be in the galactokinase, uridylyl transferase or • From glucose is carried out by the enzyme
4-epimerase. Such patients have high glycogen synthase. The activation of
concentration of galactose in blood glucoseto be used for glycogen synthesis is
(galactosemia). carried out by the enzyme UDP-glucose
➢ In lens, galactose is reduced to galactitol by pyrophosphorylase. The enzyme
aldose reductase. The product accumulates in exchanges the phosphate on C-1 of
lens leads to accumulation of water by osmotic glucose -1-phosphate for UDP
pull. This leads to turbidity of lens proteins (uridinediphosphate). The energy of the
(cataract) phospho glycosyl bond of UDP-glucose is
➢ May cause failure of liver function and mental utilized by glycogen synthase to catalize
retardation. the incorporation of glucose in to
- GLYCOGEN METABOLISM glycogen. UDP is subsequently released
➢ DEGRADATION OF GLYCOGEN (glycogenolysis) from the enzyme. The α-(1,6) branches in
• Shortening of chains glucose are produced by amylo-(1, 4-1, 6)
➔ Glycogen phosphorylase is a transglycosylase, also termed as branching
phosphotransferase that sequentially enzyme. This enzyme transfers a terminal
degrades the glycogen chains at their fragment of 6-7 glucose residues (from a
non reducing ends until four glucose polymer of atleast 11 glucose residues
units remain each chain before a long) to an internal glucose residue at the
branch point. The resulting structure C-6 hydroxyl position.
is called a limit dextrin and ➢ Glycogen synthesis disease
phosphorylase cannot degrade it any • Genetic disease that results from a defect
further. The product of this reaction is in an enzyme required for either glycogen
glucose 1 phosphate and is then synthesis or degradation.
converted to glucose 6 phosphate by • They result in either formation of glycogen
phosphoglucomutase. that has an abnormal structure or the
 accumulation of excessive amounts of • Muscle cannot form glucose by
normal glycogen in specific tissues. gluconeogenesis process because glucose
➢ Pentose Phosphate Pathway 6 phosphatase is absent. Unlike liver,
• Primarily an anabolic that utilizes the 6 muscle cannot supply glucose to other
carbons of glucose to generate 5 carbon organs inspite of having glycogen.
sugars and reducing equivalents. ➢ Gluconeogenesis
• To generate reducing equivalents, in the • The biosynthesis of new glucose from
form of NADPH, for reductive biosynthesis noncarbohydrate substances
reactions within cells. • In the absence of dietary intake of
• To provide the cell with ribose-5- carbohydrate liver glycogen can meet
phosphate (R5P) for the synthesis of the these needs for only 10-18hrs.
nucleotides and nucleic acid. • During prolonged fast hepatic glycogen
• It can operate to metabolize dietary stores are depleted and glucose is formed
pentose of sugar derived from the from precursors such as lactate, pyruvate,
digestion of nucleic acids as well as to glycerol and keto acids.
rearrange the carbon skeletons of dietary • Approximately 90% of gluconeogenesis
carbohydrates into occurs in the liver whereas kidneys provide
glycolytic/gluconeogenic intermediates. 10% of newly synthesized glucose
• Cells of liver, adipose tissue, adrenal molecules, the kidneys thus plays a minor
cortex, testis and lactating mammary role except during prolonged starvation
gland have high levels of PPP enzymes. In when they become major glucose
fact 30% if the oxidation of glucose in the producing organs.
liver occurs via the PPP. • Reactions unique to gluconeogenesis
➢ HMP SHUNT ➔ Carboxylation of pyruvate
• Metabolic pathway parallel to glycolysis. o In gluconeogenesis, pyruvate is first
• Generates NADPH and pentoses essential carboxylated by the pyruvate
in the body for various reasons. carboxylase to oxaloacetate where it is
• Allows the carbon atoms from glucose-6- converted to phosphoenolpyruvate
phosphate to take brief detour (shunt) (PEP) by the action of PEP
before the proceed down the glycolytic carboxykinase [pyruvate carboxylase is
pathway. found in the mitochondria of livers and
• All the intermediates of this pathway are in kidneys not in muscles. Thus muscle
the monophosphate from contrary to cannot provide blood glucose from
glycolysis where biphosphate forms of muscle glycogen].
intermediates are also there. o Biotin – a coenzyme of pyruvate
• An alternate route for the metabolism of carboxylase derived from vitamin B6
glucose covalently bound to the apoenzyme
➢ Coris cycle or lactic acid cycle through an ε- amino group of lysine
• occurs when the muscles need energy forming the active enzyme.
• cycle involves turning lactate into glucose o Allosteric regulation – pyruvate
because the body cannot use lactate for carboxylase is allosterically activated
energy. This is a way to bring energy to the by acetyl CoA. Elevated levels of acetyl
muscles during intense workouts and CoA may signal one of the several
other times of lower oxygen levels in the metabolic states in the increased
body. synthesis of oxaloacetate is required.
• Lactate is efficiently reutilized by the body.
• Prevents lactic acidosis in muscle.
• Important for production of energy
molecules (ATP) during muscle activity.
➔ Transport of oxaloacetate to the cytosol ➔ Substrates for gluconeogenesis
(irreversible) o Gluconeogenic precursors
o Oxaloacetate, formed in mitochondria,  Can give rise to a net synthesis of
must enter the cytosol where the glucose.
other enzymes of gluconeogenesis are  Include all intermediates of
located. However, oxaloacetate is glycolysis and the citric acid cycle.
unable to cross the inner  Glycerol is released during
mitochondrial membrane directly. It hydrolysis of triacylglycerol on
must be first reduced to malate which adipose tissue and is delivered to
can then be transported from the the liver. Glycerol is phosphorylated
mitochondria to the cytosol. In the to glycerophosphate an
cytosol, the malate is reoxidized to intermediate of glycolysis.
oxaloacetate.  Lactate is released in the blood by
➔ Decarboxylation of cytosolic oxaloacetate cell, lacking mitochondria such as
o Oxaloacetate is decarboxylated and RBC, and exercising skeletal muscle.
phosphorylated in the cytosol by PEP- o Ketogenic compound
carboxykinase. The reaction is driven by  Acetyl CoA and compounds that
hydrolysis of GTP. The combined action give rise to acetyl CoA cannot
of carboxylase and PEP carboxykinase given rise to a net synthesis of
provides an energetically favorable glucose, this is due to the
pathway from pyruvate to PEP then irreversible nature of pyruvate
enters the reversed reactions of dehydrogenase reaction. These
glycolysis until it forms fructose 1, 6- compounds give rise to ketone
biphosphate. bodies and therefore termed
➔ Dephosphorylation of fructose 1, 6- ketogenic.
biphosphate (irreversible) • Advantages of gluconeogenesis
o Hydrolysis of fructose 1, 6 biphosphate ➔ Meets the requirements of glucose in
by fructose 1, 6 biphosphate passes the body when carbohydrates are not
the irreversible PFK-1 reaction and available in sufficient amounts.
provides energetically favorable ➔ Regulate blood glucose level.
pathway for the formation of fructose ➔ Source of energy for nervous tissue
6-phosphate. and erythrocytes
o Important regulatory site of ➔ Maintain levels of intermediates of
gluconeogenesis: TCA cycle
 Regulation by energy levels within ➔ Clear the products of metabolism of
the cell other tissues (muscle).
 Regulation by fructose 2, 6 • Homeostasis of blood glucose
biphosphate ➔ Homeostasis of glucose is due to
➔ Dephosphorylation of glucose 6 phosphate balance of addition and utilization of
(irreversible) glucose. Fasting blood glucose is
o Hydrolysis of glucose 6phosphate by maintained between 80-120mg%.
glucose 6phosphatase bypasses the after a meal it rises by 40-60mg% and
irreversible hexokinase reaction returns to normal within 2-3hrs.
provides energetically favorable
pathway for the formation of free
glucose.
INTERGRATIVE METABOLISM AND BIOENERGETICS ➢ Hydrolysis of ATP or other nucleotides
I. ENERGY GENERATION AND UTILIZATION IN THE usually involves the terminal high-energy
LIVING SYSTEM phosphate bond. The phosphate transfer
- Cellular oxidation of molecules release energy, commonly involves the 2terminal phosphate
part of which is conserved through the synthesis group as pyrophosphate. Transfer of AMP
of high-energy phosphate bonds and the rest is portion of ATP is also common with
lost as heat. The high-energy phosphate bonds concomitant hydrolysis of pyrophosphate.
are directly utilized for cellular energy requiring
process. ATP is the common high-energy
phosphate bond that is formed during oxidative - Cellular formation and utilization of ATP
process. ➢ Within cells ATP continuously formed and
- Under cellular conditions energy releasing utilized
process are coupled to energy requiring cellular ➢ Serve as the principal immediate donor of
process through common energy currency, ATP. free energy biological system.
- Universal transfer agent of chemical energy ➢ Oxidation of fuel molecules
between energy-yielding and energy-requiring • Catabolism of fuel molecules occurs
cellular process. stepwise each step releasing partial
- ATP and other nucleotides of comparable energy, energy content of molecules. The
carry two high-energy phosphate bonds. The amount of total energy release depends
hydrolysis of these high-energy phosphate bonds upon the cellular conditions:
release energy which powers cellular energy ➔ Presence / absence of oxygen
requiring processes. Thioester bonds also (aerobic/anaerobic)
contain comparable energy content to that of ➔ Presence / absence of specific
ATP. Energy of hydrolysis of thioester bond is organelles with oxidative functions
mostly used to drive the reactions forward to (mitochondrial)
completion. • Catabolic reactions in addition, provide
II. HIGH ENERGY PHOSPHATE BONDS building blocks for biosynthetic reactions
- High-energy phosphate bonds: III. CATABOLISM OF FUEL MOLECULES
➢ At pH 7, ATP carries 4 – charges. -
➢ Charges repel each other because of
proximity.
➢ Repulsion is relieved upon hydrolysis of high-
energy level bonds.
➢ ATP and other high energy compounds
contain phosphoanyhydride bonds which ➢ Glycolysis – partial metabolism
release much free energy upon hydrolysis. • Small amount of energy conserved (ATP,
- Energy of hydrolysis of phosphate bonds NADH)
➢ Hydrolysis of high-energy phosphate bond of • Prepares carbohydrates for the next
ATP releases free energy of about -7.3 catabolic processes.
kcal/mol
• Sometimes the only life sustaining energy
➢ Energy reserved upon hydrolysis of high
generating process.
energy phosphate bonds may result in:
➔ RBC (lack of mitochondrion)
• Transfer of phosphate group with partial ➔ Exercising muscle (Oxygen limitation)
conversation energy by newly formed bond -
• Formation of new bond
• Change in conformation of molecules
• Signal amplification
• Transport molecules across membranes
• Some portion lost as heat
 - ATP. This occur by the help of energy conserving
system in the inner mitochondrial membrane of
eukaryotes or plasma membrane of prokaryotes.
- Aerobic energy-generation
➢ Complete breakdown of fuel molecules,
- Concept of free energy carbohydrates, fats and proteins takes place in
➢ Free energy (∆G) is that portion of the energy of a mitochondria of eukaryotes and cytoplasmic
system available to do work as the system membrane and cytoplasm of aerobic
proceeds toward equilibrium under conditions of prokaryotes.
constant temperature and pressure and volume. - Mitochondria
➢ ∆H (change in enthalpy, internal heat) and ∆S ➢ Organelle where major amount of energy
(change in entropy) produced.
➢ Free energy charge is used to predict the direction ➢ Out membrane
and equilibrium for chemical reactions. • Smooth and unfolded
• If ∆G is (-) net loss of energy (exergonic), • Freely permeable to most ions and polar
reaction goes spontaneously. molecules (contain porous channels)
• If ∆G is (+) net gain energy (endergonic), ➢ Inner membrane
reaction does not go spontaneously. • Folded into cristae-increased surface area
• If ∆G is 0 reactants are equilibrium • Highly impermeable to most ions and
- Oxidation- Reductase reactions (utilization of chemical polar molecules
energy in living system ➢ Contain transporters which access polar and
➢ Oxidation (donor) ionic molecule in and out.
• Removal of electron from substance ➢ Cristae are characteristics of muscle & other
• Usually accompanied by a decrease in energy metabolically active cell types
content of oxidized substance • Protein-rich membrane (75%)
• Reactions are coupled process ➢ Inner membrane space – space between outer
➢ Reduction (acceptor) and inner membranes
• Addition of electrons from substance ➢ Matrix – the internal compartment containing
• Usually accompanied by an increase in energy soluble enzymes and mitochondrial genetic
content of reduced substance material
IV. REDUCTION POTENTIAL (oxidation-reduction - Oxidation of pyruvate
potential E’o ➢ Pyruvate is common intermediate of many
➢ Measure of electron donating tendencies catabolic reactions. It is still energy rich in
➢ Electrically measured in reference to a standard molecule. It is a cross road molecule which can
substance H2. Determined by measuring be converted into different intermediates
electromotive force generated by a sample half- depending on type of cell-eukaryotes except
cell with respect to standard reference half-cell. RBC – acetyl CoA
• A negative E’o = lower affinity for electrons ➢ Absence or presence of oxygen -lactate,
• A positive E’o = higher affinity for electrons ethanol or acetyl-CoA
➢ In biological systems the primary electron donors • High ratio of NADH/NAD+ favors lactate
are fuel molecules such as carbohydrates, fats, and formation in actively exercising muscle
proteins. (oxygen limitation)
➢ In respiration chain the electrons from NADH are
transferred through a series of carriers until they
are accepted by molecular oxygen releasing
energy at different levels.
➢ Under cellular condition part of the free-energy of
oxidation of reducing equivalents is conserved in
the form of high-energy phosphate compound,
 ➢ Oxidation of pyruvate into acetyl CoA-aerobic • Oxidative decarboxylation of α-
process (O2 terminal electron-acceptor) which ketoglutarate by α-ketoglutarate
takes place in the mitochondrial matrix of dehydrogenase complex
eukaryotic cell pyruvate is transported into • Conversation of succinyl CoA into
mitochondrial matrix by special transporter. Inside succinate by succinate thiokinase (succinyl
the matrix pyruvate is oxidized into acetyl CoA by CoA synthase)
pyruvate dehydrogenase complex which is • Oxidation of succinate by succinate
complex of E1 (pyruvate dehydrogenase), E2 dehydrogenase
(dihydrolipoyl transacetylase), and E3 • Hydration of fumarate by fumarase
(dihydrolipoyl dehydrogenase) • Oxidation of L-malate by NAD-linked
- Regulation of pyruvate dehydrogenase malate dehydrogenase
➢ Product inhibition by: ➢ No net consumption or production of cycle
• Acetyl CoA intermediates
• Elevated levels of NADH • Oxaloacetate plays catalytic role in
➢ Covalently modification catabolism of acetyl CoA. The energy of
• Dephosphorylated (active) – increased acetyl CoA catabolism is partly conserved
ADP/ATP ratio as reducing equivalents (NADH & FADH2)
• Phosphorylated (inactive) – increased and GTP
acetyl CoA/CoA ratio & NADH/NAD+ ratio ➢ Function of kreb’s cycle
- KREBS CYCLE • Has catabolic and anabolic function
➢ Tricarboxylic acid cycle/citric acid cycle  Catabolic- when you digest food &
➢ Final common pathway for complete exudate molecules breakdown in the body for
of carbohydrates fatty acids and many amino use as energy
acids. Common pathway for catabolism of  Anabolic – build organs and tissues
acetyl CoA , a common intermediate of • Energy generation
different catabolic pathways. ➔ Reducing equivalents NADH & FADH2
➔ Provide CO2 used for gluconeogenesis,
fatty synthesis, urea synthesis &
ucleotide synthesis
➔ Provide precursors for
gluconeogenesis (all intermediates),
➢ Aerobic process (occurs in aerobic cells in amino acid synthesis (non-essential
presence of oxygen gas). Reactions take place amino acid), heme synthesis (succinyl
in cytosol of prokaryotes and mitochondria CoA), fatty acid synthesis (citrate)
matrix of eukaryotes. ➔ Regulate other pathways citrate
➢ The metabolic pathway in addition to (inhibit phosphofructokinase)
providing energy provides building blocks
required for growth, reproduction, repair and
maintenance of cellular viability.
➢ Reactions of kreb’s cycle ➔ Propionyl CoA enter the cycle as
• Condensation of acetyl CoA with succinyl CoA
oxaloacetate by citrate synthase
(condensing enzyme) to form citrate.
• Isomerization of citrate to isocitrate by
aconitase
• Oxidative decarboxylation of isocitrate by
isocitrate dehydrogenase
 ➢ Regulation of Kreb’s cycle • COMPLEX III
• Provide energy, thus rate of the cycle is
adjusted to meet an animal cell ATP
demand. • COMPLEX IV
• Controlled & regulated by the availability Oxidation of NADH releases more than
of the NAD+ & FAD substances while high enough free energy needed for synthesis
concentration inhibits it. of 3ATP.
- ELECTRON TRANSPORT SYSTEM AND OXIDATIVE ➢ COUPLING OF ELECTRON TRANSPORT AND ATP
PHOSPHORYLATION SYNTHESIS (OXIDATIVE PHOSPHORYLATION)
➢ A process occurring on the inner mitochondrial • Electron transport and oxidative
membrane of eukaryotes. phosphorylation are coupled processes.
➢ A system composed of chain of membrane • Suggested hypotheses for coupling
associated electron carriers. mechanism
➢ Components • High energy intermediate serves as a
• Flavoproteins- accept H atoms but donate precursor of ATP activated protein
electrons nonheme iron-sulfur protein. conformation drives the synthesis of ATP
• Coenzyme Q- accept H atom but donate • Proton gradient across inner
electrons. Acceptors electrons from mitochondrial membrane couples electron
flavoproteins & donate to cytochromes. transport and ATP synthesis
Transfer & accept two electrons at a time. • Electron- transport and oxidative
• Cytochromes – accepts electron from phosphorylation are coupled by proton-
CoQH2 & transfer then to the next acceptor gradient as follows. As electrons from
cytochrome w/ more positive reduction NADH/FADH2 flow down the respiratory
potential. chain to O2 free energy is released
➢ Components of electron transport chain (Mitchell’s chemiosmotic theory)
• Complexes I, III, IC are proton pumps linked
by CoQ and Cyt.c. ➢ RESPIRATORY CONTROL
• Made up of quinone and a hydrophobic • The medulla oblongata (connection
tail. Its purpose is to function as an between the brainstem and spinal cord)
electron carrier and transfer electrons to includes the respiratory center which
complex III. regulates breathing on a minute by minute
➢ Oxidation of reducing equivalents and electron basis. Respiratory rhythm is not produced
flow through respiration chain by homogeneous population of
peacemaker cell unlike the cardiac system.
➢ UNCOUPLING OF ELECTRON TRANSPORT AND
OXIDATIVE PHOSPHORYLATION
• Uncouplers – substances which uncouple
• COMPLEX 1 electron transport and oxidative
➔ Electrons from NADH enter at phosphorylation.
complex I to be relayed to CoQ ➔ Chemical uncouplers
through series of carriers Q also o Ex: 2,4-dinitrophenol accepts
acceptors a pair of FADH2 prosthetic proton and carries it into matrix
group of complex II, glycerol through membrane permeable
phosphate dehydrogenase and fatty ➔ Physiological uncoupler
acyl dehydrogenase. o Abundant in mitochondria of
brown adipose tissue –
absent/reduced in obese
individuals
 o Responsible for diet induced
thermogenesis
o Present in newborns and cold
adapted individuals
o Thermogenin is opened by fatty
acids liberated upon degradation
of stored fat by activated
hormone sensitive lipase by
norepinephrine released in
response to drop in body temp.
due to cold environment.
o Opening of thermogenin allows
reentry of translated protons
through IMM
o No ATP synthesis
o Energy of oxidation lost as heat
➢ RESPIRATION POISONS
• Inhibit electron flow through respiratory
chain
• Inhibit proton translocation
• Inhibit proton gradient formation
• Inhibit oxygen gas consumption
• Inhibit ATP synthesis reducing equivalents
remain reduces