CARBOHYDRATE

METABOLISM
• Digestion is the process of hydrolysing large and complex food materials
into the smaller and simpler form in the GIT.
• The major food stuffs are carbohydrates, proteins,and fats
• Digestion is brought about by the action of enzymes that are present in
different digestive juices like saliva, gastric juice, pancreatic juice.
• During the process of digestion , polysaccharides and disaccharides are
converted to monosaccharides ,proteins into amino acids, and fats into
glycerol and fatty acids.
• These simpler forms are ready for absorption
• Absorption is the transport of digested products from the intestinal lumen
into the blood or lymph across the intestinal mucosal cells
• The small intestine is the main absorptive organ
• Water is mainly absorbed in the large intestine.
• Adsorption of substances into the intestinal cells involves the passage
of substances across the cell membrane and it take place by 3
processes.
1. Simple diffusion- Does not require carrier molecule and energy
2. Facilitated transport-Requires a carrier protein,but does not
requires energy
3. Active transport-Requires both carrier protein molecule and energy
• Digestion of carbohydrates
• The mainly dietary carbohydrates are polysaccharides(starch) and
disaccharides(sucrose and lactose).small amounts of
monosaccharides(fructose,glucose and pentoses)and dextrins are
also present in the food
• Generally starch forms more than 50%of carbohydrates in human
food
• Digestion of carbohydrates occurs briefly in mouth and largely in
intestine
• A) Digestion of starch
• Digestion of starch begins in mouth and continues in intestine
• Salivary amylase and pancreatic amylase are the important enzymes
of starch digestion .chloride is an activator of these enzymes.
• 1) Digestion in the mouth
• Salivary amylase of saliva starts the digestion of cooked starch in the
mouth. very little digestion take place in the mouth as the food
remains in the mouth for a very short period of time.
• II)Digestion in the stomach
• When the foods get mixed with gastric juice,the action of amylase
stops due to acidity(pH of gastric content is less than 3 due to the
presence of HCl which denatures and inactivates salivary amylase)
• III)Digestion in the small intestine
• Pancreatic amylase continues the digestion of starch in the intestine.
• Action is similar to salivary amylase
• Further digestion of these disaccharides and oligosaccharides
• The final digestion of these disaccharides and oligosaccharides is
carried out by disaccharidases(Maltase and Isomaltase enzyme)which
are present in the brush border of the small intestine.
• These enzymes are also referred to as brush border enzymes
• Maltase digest maltose,maltotriose,unbranched oligosaccharides.
• Isomaltase digest isomaltase as it breaks alpha- 1,6 bonds.

• B)Digestion of sucrose
• Brush border enzyme sucrase hydrolyses sucrose into a molecule of
glucose and a molecule of fructose
• Some sucrose is digested in the stomach by HCl
• C)Digestion of lactose
• Brush border enzyme lactase ,hydrolyses lactose into a molecule of
glucose and a molecule of galactose
• D)Digestion of trehalose
• Brush border enzyme trehalose ,hydrolyses trehalose into 2
molecules of glucose
• Absorption of carbohydrates
• The products of carbohydrate digestion are mainly glucose and small
Amounts of fructose and galactose molecules.
• Glucose ,fructose, and galactose are absorbed by facilitated diffusion
• Facilitated diffusion requires a carrier protein, but doesn’t require
energy
• A carrier protein called Sodium independent transporter(GLUT
5)transport glucose,fructose and galactose from the intestinal lumen
to intestinal mucosa
• Glucose and galactose are also absorbed by active transport
• Active transport requires both carrier protein and energy
• A carrier protein called sodium dependent glucose transporter
(SGLT1)binds both glucose and sodium at separate sites and transport
them from intestinal lumen to intestinal mucosa cells.This is symport
transport mechanism.
• Transport of monosaccharides from intestinal cells to the capillaries
• Glucose and other monosaccharides are transported from the
intestinal cells into the capillaries by GLUT 2(sodium independent
glucose transporter)
• It is a uniport facilitated diffusion system
• Abnormalities of carbohydrate metabolism
• Lactose intolerance
• Deficiency of lactase enzyme leads to lactose intolerance
• Lactase is present in brush border of intestine
• This enzyme hydrolyses lactose to glucose and galactose
• In lactose intolerance ,lactase cannot be digested by the affected
person.
• There are 3 types of lactose intolerance
1. Inherited lactose deficiency –Rare ,seen in infants
2. Primary low lactose activity-most common, manifested in adults
3. Secondary low lactose activity
• Clinical manifestation
• bloating
• diarrhea
• nausea
• Pain in the abdomen
• vomiting
• Treatment
• Elimination of milk and milk products from the diet
• Curd is an effective treatment as lactobacilli present in curd contains
the enzyme lactase
• Hundreds of reactions simultaneously take place in a living cell, in a
well-organized and integrated manner.
• The entire spectrum of chemical reactions, occurring in the living
system, are collectively referred to as metabolism.
• A metabolic pathway (or metabolic map) constitutes a series of
enzymatic reactions to produce specific products.
• The term metabolite is applied to a substrate or an intermediate or a
product in the metabolic reactions
• Metabolism is divided into two categories
• Catabolism and Anabolism
• 1. Catabolism : The degradative processes concerned with the
breakdown of complex molecules to simpler ones,
• 2. Anabolism : The biosynthetic reactions involving the formation of
complex molecules from simple precursors
• MAJOR PATHWAYS OF CARBOHYDRATE MEBOLISM ARE
• (1) Glycolysis
• (2) Citric acid cycle
• (3) Gluconeogenesis
• (4) Glycogenesis
• (5) Glycogenolysis
• (6) Hexose monophosphate shunt
• GLYCOLYSIS (EMBDEN-MEYERHOFPARNAS PATHWAY)
• In glycolytic pathway glucose is converted to pyruvate (aerobic
condition) or lactate (anaerobic condition), along with production of a
small quantity of energy.
• Glycolysis is derived from the Greek words, glykys = sweet; and lysis =
splitting.
• Site of reactions: All the reaction steps take place in the cytoplasm.
• Significance of Glycolysis Pathway
1. It is the only pathway that is taking place in all the cells of the body.
2. Glycolysis is the only source of energy in erythrocytes.
3. In strenuous exercise, when muscle tissue lacks enough oxygen,
anaerobic glycolysis forms the major source of energy for muscles.
4. The glycolytic pathway provides carbon skeletons for synthesis of
non-essential amino acids as well as glycerol part of fat.
5. Most of the reactions of the glycolytic pathway are reversible,
which are also used for gluconeogenesis
Steps of Glycolytic Pathway

Step 1 of Glycolysis
i. Glucose is phosphorylated to glucose-6-phosphate
ii. The enzyme is Hexokinase (HK), which splits the ATP into ADP, and the Pi is added
on to the glucose.
iii . Hexokinase is a key glycolytic enzyme. The kinase reaction is irreversible.
iv. Hexokinase and glucokinase may be considered as iso-enzymes;
Glucokinase is under the influence of insulin; but hexokinase is not. Hexokinase is
present in most tissues. Glucokinase with a high Km for glucose is present in liver
and beta cells.

Step 2 of Glycolysis
I .Glucose-6-phosphate is isomerized to fructose-6-phosphate by phosphohexose
isomerase. This is readily reversible
Step 3 of Glycolysis
i. Fructose-6-phosphate is further phosphorylated to fructose1,6-bisphosphate. The
enzyme is phosphofructokinase.
ii. Phosphofructokinase (PFK) is the rate limiting enzyme of glycolysis. It is an
allosterically regulated enzyme
iii. The steps 1,2 and 3 together are called as the preparatory phase.

Step 4 of Glycolysis
I The 6 carbon fructose-1,6-bisphosphate is cleaved into two 3 carbon units; one
glyceraldehyde-3-phosphate and another molecule of dihydroxy acetone phosphate
by the enzyme Aldolase

Step 4-A of Glycolysis

I .Dihydroxyacetone phosphate is isomerized to glyceraldehyde-3-phosphate by the
enzyme phosphotriose isomerase
Step 5 of Glycolysis
I .Glyceraldehyde-3-phosphate is dehydrogenated and simultaneously
phosphorylated to 1,3-bisphosphoglycerate (1,3-BPG) with the help of NAD+ . The
enzyme is glyceraldehyde-3-phosphate dehydrogenase. The product contains a high
energy bond. This is a reversible reaction.

Step 6 of Glycolysis
i.The energy of 1,3-BPG is trapped to synthesize one ATP molecule with the help of
phosphoglycerate kinase and formation of 3 phosphoglycerate
ii. This is an example of substrate level phosphorylation, where energy is trapped
directly from the substrate, without the help of the complicated electron transport
chain reactions.

Step 7 of Glycolysis
I. 3-phosphoglycerate is isomerized to 2-phosphoglycerate .The enzyme is
phosphoglyceromutase. This is a readily reversible reaction.
Step 8 of Glycolysis
i. 2-phosphoglycerate is converted to phosphoenol pyruvate by the enzyme
enolase. One water molecule is removed
ii. A high energy phosphate bond is produced. The reaction is reversible.

Step 9 of Glycolysis
During the reaction, PEP is first converted to the enol intermediate and then to keto
pyruvate, the stable form.
i. Phosphoenol pyruvate (PEP) is dephosphorylated to pyruvate, by pyruvate kinase.
First PEP is made into a transient intermediary of enol pyruvate; which is
spontaneously isomerized into keto pyruvate, the stable form of pyruvate
ii. The pyruvate kinase is a key glycolytic enzyme. This step is irreversible.
Step 10 of Glycolysis
• In anaerobic condition, pyruvate is reduced to lactate by lactate
dehydrogenase (LDH) (Greek; an=not; aer=air; bios=life). LDH has 5 iso-
enzymes.

• In aerobic conditions, the pyruvate enters the citric acid cycle for complete
oxidation. The end product of anaerobic glycolysis is lactate which enters the
Cori's cycle.
Regulation of Glycolysis
1. Hexokinase, step 1 (glucokinase, in liver)
2. Phosphofructokinase, (step 3)
3 . Pyruvate kinase,( step 9)
• Hexokinase is inhibited by glucose 6-phosphate. This enzyme prevents the
accumulation of glucose 6-phosphate due to product inhibition.
• Phosphofructokinase (PFK) is the most important regulatory enzyme in
glycolysis.
• This enzyme catalyses the rate limiting committed step.
• PFK is an allosteric enzyme regulated by allosteric effectors. ATP, citrate and
H+ ions (low pH) are the most important allosteric inhibitors, whereas,
fructose 2,6-bisphosphate, ADP, AMP and Pi are the allosteric activators.
• Pyruvate kinase also regulates glycolysis. This enzyme is inhibited by ATP and
activated by F1,6-BP. Pyruvate kinase is active (a) in dephosphorylated state
and inactive (b) in phosphorylated state
Lactic acidosis
• Lactic acid is a three carbon hydroxy acid.
• Elevation of lactic acid in the circulation (normal plasma 4–15 mg/dl) may occur due
to its increased production or decreased utilization.
• Mild forms of lactic acidosis (not life-threatening) are associated with strenuous
exercise, shock, respiratory diseases, cancers, low pyruvate dehydrogenase activity,
Cori's Cycle or Lactic Acid Cycle
i. Definition: It is a process in which glucose is converted to lactate in the muscle;
and in the liver this lactate is re-converted into glucose
ii. In an actively contracting muscle, pyruvate is reduced to lactic acid which may
tend to accumulate in the muscle. The muscle cramps, often associated with
strenuous muscular exercise, are thought to be due to lactate accumulation.
iii. To prevent the lactate accumulation, body utilizes Cori's cycle.
iv. Lactic acid from muscle diffuses into the blood. Lactate then reaches liver, where
it is oxidized to pyruvate. Thus it is channeled to gluconeogenesis. Regenerated
glucose can enter into blood and then to muscle. This cycle is called Cori's cycle
v. Significance of the Cori's cycle: The lactate produced in the muscle is efficiently
reutilized by the body. But this is an energy-expensive process. During exercise,
lactate production is high, which is utilized by liver to produce glucose. The process
needs ATP.
Rapaport Leubering Cycle (BPG Shunt)
• This is a supplementary pathway to glycolysis which is operative in the erythrocytes of
man and other mammals.
• Rapaport-Leubering cycle is mainly concerned with the synthesis of 2,3-
bisphosphoglycerate (2,3-BPG) in the RBC.
• 1,3-Bisphosphoglycerate (1,3-BPG) produced in glycolysis is converted to 2,3-BPG by
the enzyme 2,3-bisphosphoglycerate mutase. 2,3-BPG is hydrolysed to 3-
phosphoglycerate by bisphosphoglycerate phosphatase
Significance of BPG
1. Under hypoxicconditionsthe2,3-BPGconcentration in the RBC increases, thus favoring
the release of oxygen to the tissues even when pO2 is low.
2. In this shunt pathway, no ATP is generated.
 CITRIC ACID CYCLE

• The citric acid cycle (Krebs cycle or tricarboxylic acid—TCA cycle) is

the most important metabolic pathway for the energy supply to
the body.
• About 65-70% of the ATP is synthesized in Krebs cycle.
• Citric acid cycle essentially involves the oxidation of acetyl CoA to
CO2 and H2O
• The citric acid cycle is the final common oxidative pathway for
carbohydrates, fats and amino acids.
• This cycle not only supplies energy but also provides many
intermediates required for the synthesis of amino acids, glucose,
heme etc.
• Krebs cycle is the most important central pathway connecting
almost all the individual metabolic pathways (either directly or
indirectly)
• The enzymes of TCA cycle are located in mitochondrial matrix, in close proximity
to the electron transport chain.
• Krebs cycle basically involves the combination of a two carbon acetyl CoA with a
four carbon oxaloacetate to produce a six carbon tricarboxylic acid, citrate.

Reactions of citric acid cycle

1. Formation of citrate : Krebs cycle proper starts with the condensation of acetyl
CoA and oxaloacetate, catalysed by the enzyme citrate synthase.
2. and 3. Citrate is isomerized to isocitrate by the enzyme aconitase. This is achieved
in a two stage reaction of dehydration followed by hydration through the formation
of an intermediate—cis-aconitate
4. and 5. Formation of alpha-ketoglutarate : The enzyme isocitrate dehydrogenase
(ICD) catalyses the conversion (oxidative decarboxylation) of isocitrate to
oxalosuccinate and then to alpha-ketoglutarate
6. Conversion of alpha-ketoglutarate to succinyl CoA occurs through oxidative
decarboxylation, catalysed by alpha-ketoglutarate dehydrogenase complex. This enzyme
is dependent on five cofactors—TPP, lipoamide, NAD+, FAD and CoA
7. Formation of succinate : Succinyl CoA is converted to succinate by succinate thiokinase.
This reaction is coupled with the phosphorylation of GDP to GTP. This is a substrate level
phosphorylation. GTP is converted to ATP by the enzyme nucleoside diphosphate kinase.
8. Conversion of succinate to fumarate : Succinate is oxidized by succinate dehydrogenase
to fumarate
9. Formation of malate : The enzyme fumarase catalyses the conversion of fumarate to
malate with the addition of H2O.
10. Conversion of malate to oxaloacetate : Malate is then oxidized to oxaloacetate by
malate dehydrogenase. The third and final synthesis of NADH occurs at this stage. The
oxaloacetate is regenerated which can combine with another molecule of acetyl CoA, and
continue the cycle.
• Energetics of citric acid cycle During the process of oxidation of acetyl CoA via citric acid
cycle, 4 reducing equivalents (3 as NADH and one as FADH2) are produced.
• Oxidation of 3 NADH by electron transport chain coupled with oxidative phosphorylation
results in the synthesis of 9 ATP, whereas FADH2 leads to the formation of 2 ATP.
• Besides, there is one substrate level phosphorylation. Thus, a total of twelve ATP (10 as
per recent evidence) are produced from one acetyl CoA.

Role of vitamins in TCA cycle Four B-complex vitamins are essential for Krebs cycle, and
thus energy generation
1. Thiamine (as TPP) as a coenzyme for D-ketoglutarate dehydrogenase
2. Riboflavin (as FAD) as a coenzyme for succinate dehydrogenase.
3. Niacin (as NAD+) as electron acceptor for isocitrate dehydrogenase, D-ketoglutarate
dehydrogenase and malate dehydrogenase.
4. Pantothenic acid (as coenzyme A) attached to active carboxylic acid residues i.e.
acetyl CoA, succinyl CoA
Regulation of citric acid cycle
Three enzymes—namely citrate synthase, isocitrate dehydrogenase and D-ketoglutarate
dehydrogenase—regulate citric acid cycle.

1. Citrate synthase is inhibited by ATP, NADH, acetyl CoA and succinyl CoA.

2. Isocitrate dehydrogenase is activated by ADP, and inhibited by ATP and NADH

3. D-Ketoglutarate dehydrogenase is inhibited by succinyl CoA and NADH

The citric acid cycle provides various intermediates for the synthesis of many compounds
needed by the body. Krebs cycle is both catabolic and anabolic in nature, hence regarded as
amphibolic
GLUCONEOGENESIS
• The synthesis of glucose from noncarbohydrate compounds is known as
gluconeogenesis.
• The major substrates/precursors for gluconeogenesis are lactate, pyruvate, glucogenic
amino acids, propionate and glycerol
• LOCATION OF GLUCONEOGENESIS
• Gluconeogenesis occurs mainly in the cytosol, although some precursors are produced
in the mitochondria.
• Gluconeogenesis mostly takes place in liver (about 1 kg glucose synthesized everyday)
and, to some extent, in kidney matrix
• IMPORTANCE OF GLUCONEOGENESIS
• Glucose occupies a key position in the metabolism and its continuous supply is
absolutely essential to the body for a variety of functions
• 1. Brain and central nervous system, erythrocytes, testes and kidney medulla are
dependent on glucose for continuous supply of energy. Human brain alone requires
about 120 g of glucose per day, out of about 160 g needed by the entire body.
2. Glucose is the only source that supplies energy to the skeletal muscle, under anaerobic
conditions.
3. In fasting even more than a day, gluconeogenesis must occur to meet the basal
requirements of the body for glucose and to maintain the intermediates of citric acid cycle.
This is essential for the survival of humans and other animals.

REACTION OF GLUCONEOGENESIS
• Gluconeogenesis closely resembles the reversed pathway of glycolysis, although it is not
the complete reversal of glycolysis.
• Essentially, 3 (out of 10) reactions of glycolysis are irreversible.
• The seven reactions are common for both glycolysis and gluconeogenesis
• The three irreversible steps of glycolysis are catalysed by the enzymes, namely
hexokinase, phosphofructokinase and pyruvate kinase. These three stages—bypassed
by alternate enzymes specific to gluconeogenesis—are discussed
• 1. Conversion of pyruvate to phosphoenolpyruvate :
• This takes place in two steps Pyruvate carboxylase is a biotin— dependent
mitochondrial enzyme that converts pyruvate to oxaloacetate in presence of ATP and
CO2. This enzyme regulates gluconeogenesis and requires acetyl CoA for its activity
• In the cytosol, phosphoenolpyruvate carboxykinase converts oxaloacetate to
phosphoenolpyruvate. GTP or ITP (not ATP) is used in this reaction.

• 2. Conversion of fructose 1,6-bisphosphate to fructose 6-phosphate :

Phosphoenolpyruvate undergoes the reversal of glycolysis until fructose 1,6-
bisphosphate is produced. The enzyme fructose 1,6-bisphosphatase converts fructose
1,6-bisphosphate to fructose 6-phosphate. This enzyme requires Mg2+ ions. Fructose
1,6- bisphosphatase is absent in smooth muscle and heart muscle. This enzyme is also
regulatory in gluconeogenesis.
• 3. Conversion of glucose 6-phosphate to glucose : Glucose 6-phosphatase catalyses the
conversion of glucose 6-phosphate to glucose.
Regulation of gluconeogenesis
• Influence of glucagon : This is a hormone, secreted by D-cells of the pancreatic islets.
Glucagon stimulates gluconeogenesis by two mechanisms
• 1. Active form of pyruvate kinase is converted to inactive form through the
mediation of cyclic AMP, brought about by glucagon. Decreased pyruvate kinase
results in the reduced conversion of phosphoenol pyruvate to pyruvate and the
former is diverted for the synthesis of glucose.
• 2. Glucagon reduces the concentration of fructose 2,6-bisphosphate. This compound
allosterically inhibits phosphofructokinase and activates fructose 1,6-bisphosphatase,
both favour increased gluconeogenesis
• Availability of substrates : Among the various substrates, glucogenic amino acids have
stimulating influence on gluconeogenesis.
 GLYCOGEN METABOLISM

• Glycogen is the storage form of glucose in animals, as is starch in

plants.
• It is stored mostly in liver (6-8%) and muscle (1-2%).
• Due to more muscle mass, the quantity of glycogen in muscle (250
g) is about three times higher than that in the liver (75 g).
• Glycogen is stored as granules in the cytosol, where most of the
enzymes of glycogen synthesis and breakdown are present.
• Functions of glycogen The prime function of liver
glycogen is to maintain the blood glucose levels,
particularly between meals.
• Liver glycogen stores increase in a well-fed state
which are depleted during fasting.
• Muscle glycogen serves as a fuel reserve for the
supply of ATP during muscle contraction.
GLYCOGENESIS
• The synthesis of glycogen from glucose is glycogenesis .
• Glycogenesis takes place in the cytosol and requires ATP and UTP, besides glucose.

• 1. Synthesis of UDP-glucose : The enzymes hexokinase (in muscle) and glucokinase (in liver)
convert glucose to glucose 6-phosphate. Phosphoglucomutase catalyses the conversion of
glucose 6-phosphate to glucose 1-phosphate. Uridine diphosphate glucose (UDPG) is
synthesized from glucose 1-phosphate and UTP by UDP-glucose pyrophosphorylase

2. Requirement of primer to initiate glycogenesis : A small fragment of pre-existing glycogen

must act as a ‘primer’ to initiate glycogen synthesis
3. Glycogen synthesis by glycogen synthase : Glycogen synthase is responsible for the
formation of 1,4-glycosidic linkages. This enzyme transfers the glucose from UDP-glucose
to the non-reducing end of glycogen to form alpha-1,4 linkages.

4. Formation of branches in glycogen : Glycogen synthase can catalyse the synthesis of a

linear unbranched molecule with 1,4 alpha-glycosidic linkages. Glycogen, however, is a
branched tree-like structure. The formation of branches is brought about by the action of
a branching enzyme, namely glucosyl alpha-4-6 transferase
GLYCOGENOLYSIS

The degradation of stored glycogen in liver and muscle constitutes glycogenolysis.

1. Action of glycogen phosphorylase : The alpha-1,4-glycosidic bonds (from the non-
reducing ends) are cleaved sequentially by the enzyme glycogen phosphorylase to yield
glucose 1-phosphate. This process—called phosphorolysis
2. continues until four glucose residues remain on either side of branching point (alpha-
1,6- glycosidic link). The glycogen so formed is known as limit dextrin which cannot be
further degraded by phosphorylase.
3. Action of debranching enzyme : The branches of glycogen are cleaved by two enzyme
activities present on a single polypeptide called debranching enzyme, hence it is a
bifunctional enzyme.
4. Formation of glucose 6-phosphate and glucose : Through the combined action of
glycogen phosphorylase and debranching enzyme, glucose 1-phosphate
5. Glucose 1-phosphate is converted to glucose 6-phosphate by the enzyme
phosphoglucomutase
• The fate of glucose 6-phosphate depends on the tissue.
• The liver, kidney and intestine contain the enzyme glucose 6-phosphatase that
cleaves glucose 6-phosphate to glucose.
• This enzyme is absent in muscle and brain, hence free glucose cannot be produced
from glucose 6-phosphate in these tissues
• In the peripheral tissues, glucose 6-phosphate produced by glycogenolysis will be
used for glycolysis
• Regulation of glycogenesis and glycogenolysis

• A good coordination and regulation of glycogen synthesis and its degradation are
essential to maintain the blood glucose levels.
• Glycogenesis and glycogenolysis are, respectively, controlled by the enzymes
glycogen synthase and glycogen phosphorylase.
• Regulation of these enzymes is accomplished by three mechanisms
• 1. Allosteric regulation
• 2. Hormonal regulation
• 3. Influence of calcium
1. Allosteric regulation of glycogen metabolism :
• There are certain metabolites that allosterically regulate the activities of glycogen
synthase and glycogen phosphorylase.
• The control is carried out in such a way that glycogen synthesis is increased when
substrate availability and energy levels are high. On the other hand, glycogen
breakdown is enhanced when glucose concentration and energy levels are low.
•
• 2. Hormonal regulation of glycogen metabolism : The hormones, through a complex
series of reactions, bring about covalent modification, namely phosphorylation and
dephosphorylation of enzyme proteins which, ultimately control glycogen synthesis or
its degradation.
• The overall effect of hormones on glycogen metabolism is that an elevated glucagon or
epinephrine level increases glycogen degradation whereas an elevated insulin results in
increased glycogen synthesis
• 3. Effect of Ca2+ ions on glycogenolysis :
• When the muscle contracts, Ca2+ ions are released from the sarcoplasmic reticulum.
Ca2+ binds to calmodulin-calcium modulating protein and directly activates phosphorylase
kinase without the involvement of cAMP-dependent protein kinase.
HEXOSE MONOPHOSPHATE SHUNT
• Hexose monophosphate pathway or HMP shunt is also called pentose phosphate
pathway or phosphogluconate pathway.
• This is an alternative pathway to glycolysis and TCA cycle for the oxidation of glucose.
However, HMP shunt is more anabolic in nature, since it is concerned with the
biosynthesis of NADPH and pentoses
• The enzymes of HMP shunt are located in the cytosol. The tissues such as liver, adipose
tissue, adrenal gland, erythrocytes, testes and lactating mammary gland, are highly
active in HMP shunt
• Reactions of the pathway The sequence of reactions of HMP shunt is divided into two
phases—oxidative and non-oxidative.
• 1. Oxidative phase :
• Glucose 6-phosphate dehydrogenase (G6PD) is an NADP-dependent enzyme that
converts glucose 6-phosphate to 6-phosphogluconolactone.
• The latter is then hydrolysed by the gluconolactone hydrolase to 6-phosphogluconate
• . The next reaction involving the synthesis of NADPH is catalysed by 6-
phosphogluconate dehydrogenase to produce 3 keto 6-phosphogluconate which then
undergoes decarboxylation to give ribulose 5-phosphate
G6PD regulates HMP shunt : The first reaction catalysed by G6PD is most regulatory in
HMP shunt.

2. Non-oxidative phase
• Ribulose 5-phosphate is acted upon by an epimerase to produce xylulose 5-phosphate
• while ribose 5-phosphate ketoisomerase converts ribulose 5-phosphate to ribose 5-
phosphate
• The enzyme transketolase catalyses the transfer of two carbon moiety from xylulose 5-
phosphate to ribose 5-phosphate to give a 3-carbon glyceraldehyde 3-phosphate and a
7-carbon sedoheptulose 7-phosphate.
• Transaldolase brings about the transfer of a 3-carbon fragment (active
dihydroxyacetone) from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to
give fructose 6-phosphate and four carbon erythrose 4-phosphate
• Transketolase acts on xylulose 5-phosphate and transfers a 2-carbon fragment
(glyceraldehyde) from it to erythrose 4-phosphate to generate fructose 6-phosphate
and glyceraldehyde 3-phosphate. Fructose 6-phosphate and glyceraldehyde 3-
phosphate can be further catabolized through glycolysis and citric acid cycle