Carbohydrates are the sugars, starches and fibers found in fruits, grains, vegetables and milk products. Though often maligned in trendy diets, carbohydrates — one of the basic food groups — are important to a healthy diet.

1. Carbohydrate 3
Md. Saiful Islam
B.Pharm, MPharm (PCP)
North South University
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2. Fate of pyruvate in Anaerobic condition:
Lactate
dehydrogenase
Alcoholic farmentation of pyruvate:
Pyruvate Acetaldehyde + CO2 EthanolPyruvate
decarboxylase
Alcohol
dehydrogenase
Yeast and some microorganisms farments glucose to ethanol
and carbondioxide rather than to lactate

3. Glycogenesis:
• Glycogenesis is an important metabolic activity in which molecules
of glucose in the body is converted to glycogen in order to be
stored. Glycogenesis is activated during high glucose level in the
blood (due to high carbohydrate diet or due to diabetes).
Synthesis of glycogen largely depends on the energy and glucose
levels in the body.
• So glycogenesis is a process to stores glucose by converting
glucose to glycogen.
• Operates when high levels of glucose-6-phosphate are formed in
the first reaction of glycolysis.
• It does not operate when energy stores (glycogen) are full, which
means that additional glucose is converted to body fat.
• Site of glycogenesis: Liver and muscle

4. Glycogen
Glucose 1-P
Glycogen Phosphorylase
Glucose 6-P
Fructose 6-P
Glycolytic
pathway
Phosphoglucomutase
Glycogenolysis: break down of glycogen to glucose which occurs
during starvation
Liver and kidney have glucose-6-
phosphatase enzyme which help to
convert Glucose from Glu-6-PO4,
Muscle cell devoids this enzyme.

5. CH2
CH2
P P
CH2
CH2
OH
OH
CH2
OH
OH
CH2
G Phosphorylase b,
inactive form
Phosphorylase b,
active form
AMP AMP
AMP bound to allosteric site
AMP, +ve
modulator
AMP
Regulation of glycogen
phosphorylase
ATP, –ve
modulator
Muscle
Glycogen phosphorylase can
be activated through
phosphorylation of serine
residue by phosphorylase
kinase or through AMP
binding in allosteric site.
Muscle cell has both the
systems but in liver it is
activated through
phosphorylation only.
The enzyme is inactivated
through dephosphorylation
by phosphorylase
phosphatase, ample
amounts of ATP also
inactivate this enzyme.

6. Gluconeogenesis:
• The synthesis of glucose from carbon atoms or carbon
backbones of non-carbohydrate compounds eg, from lactate,
amino acids, glycerol and propionate.
• Required when glycogen stores are depleted.
• Site of gluconeogenesis: liver and kidney.
• Not happens in skeletal muscle, heart muscle, smooth muscle
and Adipose tissue because of the deficiency of respective
enzymes

7. gluco neo genesis
Glucose (re)new make/
create
Glycolysis
glucose
Pyruvate/
Lactate
Gluconeogenesis

8. Reactions of Gluconeogenesis:
There are 10 sequential reactions of glycolysis, of which 7 are reversible and
3 are irreversible. For gluconeogenesis it needs to 3 bipass or alternative
reactions for the 3 irreversible reactions of glycolysis.
The 3 bipass reactions are as follows:
1.Pyruvate Oxaloacetate Phosphoenolpyruvate
Pyruvate
carboxylase
PEP carboxylase
2. Fructose 1,6 bisphosphate Fructose 6 phosphate
Fructose 1,6-
bisphosphatase
3. Glucose 6 phosphate Glucose
Glucose 6-phosphatase

9. Cori Cycle
• When anaerobic conditions occur in active muscle, glycolytic end product
pyruvate converts to lactate.
• The lactate moves through the blood stream to the liver, where it is
oxidized back to pyruvate.
• Gluconeogenesis converts pyruvate to glucose in liver cells, which is
carried back to the muscles.
• The Cori cycle is the flow of lactate and glucose between the muscles
and the liver.

10. Pentose phosphate pathway (PPP)
Ribose-5-phosphate
Ribulose-5-phosphate
isomerase
The pentose phosphate pathway is a
process that generates NADPH and
pentoses (5-carbon sugars). This
pathway is an alternative to glycolysis.
For most organisms, it takes place in
the cytosol; in plants, most steps take
place in plastids.
Importance of PPP:
The generation of NADPH, used in Fatty
acid synthesis.
Production of ribose-5-phosphate (R5P),
used in the synthesis of nucleotides and
nucleic acids.
Production of erythrose-4-phosphate
(E4P), used in the synthesis of aromatic
amino acids.
Erythrose-4-Phosphate
Glyceraldehyde-3-Phosphate

11. Adenosine Triphosphate (ATP)
• Used primarily as the “chemical-storage” form of energy within
the cell.

12. Nicotinamide Adenine Dinucleotide (NAD)
• Used primarily in the cell as an electron carrier to mediate
numerous reactions
Reduction
Oxidation

13. Reactions of Glycolysis are localized in Cytosol, and do not require any
oxygen.
whereas pyruvate dehydrogenase and TCA cycle reactions take place
in mitochondria where oxygen is utilized to generate ATP by oxydative
phosphorylation.
Pyruvate dehydrogenase
Complex:
Pyruvate dehydrogenase;
dihydrolipoyl transacetylase;
dihydrolipoyl dehydrogenase
Cofactors: TPP, NAD,
FAD, CoA, Lipoic acid

15. Components of Pyruvate dehydrogenase Complex (PDC)
It is a multi-enzyme complex containing three enzymes associated together
non-covalently:
E-1 : Pyruvate dehydrogenase, uses Thiamine pyrophosphate (TPP) as
cofactor
E-2 : Dihydrolipoyl transacetylase, Lipoic acid bound, CoA as substrate
E-3 : Dihydrolipoyl Dehydrogenase FAD bound, NAD+ as substrate
Advantages of multienzyme complex:
1. Higher rate of reaction: Because product of one enzyme acts as a
substrate of other, and is available for the active site of next enzyme
without much diffusion.
2. Minimum side reaction and coordinated control.

16. Regulation of pyruvate dehydrogenase:
Active pyruvate dehydrogenase
(dephosphorylated)
Pyruvate dehydrogenase
phosphate (inactive)
Pyruvate
dehydrogenase
kinase, ATP
Pyruvate
dehydrogenase
phosphate
phosphatase
ATP, serves as
stimulatory
modulator
Ca2+, Mg2+,
ATP
Pyruvate dehydrogenase is strongly inhibited by ATP, acetyl-CoA,
NADH and fatty acids. Thus the active form of the pyruvate
dehydrogenase is turned off when ample fuel is available in the form of
fatty acids and acetyl-CoA and when Cell’s ATP and its NADH/NAD+
ratio are high.

17. Thiamin (VitaminB1) deficiency in Glucose Metabolism:
Thiamine pyrophosphate (TPP) is an important cofactor of pyruvate
dehydrogenase complex, or PDC a critical enzyme in glucose
metabolism. Thiamine is neither synthesized nor stored in good
amounts by most vertebrates. It is required in the diets of most
vertebrates. Thiamine deficiency ultimately causes a fatal disease
called Beriberi characterized by neurological disturbances,
paralysis, atrophy of limbs and cardiac failure. Note that brain
exclusively uses aerobic glucose catabolism for energy and PDC is
very critical for aerobic catabolism. Therefore thiamine deficiency
causes severe neurological symptoms.

18. OH HS S
O As + O As + 2H2O
OH HS S
R R
Arsenic Poisoning in Glucose Metabolism: Arsenic compounds such
as arsenite (AsO3---) or organic arsenicals are poisonous because they
covalently bind to sulfhydryl compounds (SH- groups of proteins and
cofactors). Dihydrolipoyl group is a critical cofactor of PDC, and it has
two-SH groups, which are important for the PDC reaction. These –SH
groups are covalently inactivated by arsenic compounds as shown below
and pyruvate can not be converted to acetyl CoA, thus energy production
ceases.

19. TCA Cycle

21. 1. Citrate synthase:
Condensation of acetyl-CoA and oxaloacetate to form citrate. In this
reaction the methyl carbon of the acetyl group of acetyl-CoA condenses
with the cabonyl group of oxaloacetate.
Citrate synthase is a regulatory enzyme and this is a rate-limiting step
of the citric acid cycle. Acetyl-CoA, succinyl-CoA, NADH and fatty
acyl-CoA inhibits citrate synthase.

22. 2. Aconitase: This enzyme catalyses the reversible transformation of citrate into
isocitrate through the intermediary formation of cis-aconitate. Aconitase
promotes the reversible addition of H2O to the double bond of cis-aconitate in
two different ways, one leading to citrate and the other to isocitrate.

23. 3. Isocitrate dehydrogenase: There are two isoforms of this enzyme,
one uses NAD+ and other uses NADP+ as electron acceptor, both are
found in mitochondria. Isocitrate dehydrogenase requires Mg2+ or Mn2+
and is virtually inactive in the absence of its positive modulator ADP.

24. 4. -Ketoglutarate dehydrogenase: This is a complex of different
enzymatic activities similar to the pyruvate dehydogenase complex.
-Ketoglutarate undergoes oxidative decarboxylation to form
succinyl CoA and CO2. It has the same mechanism of reaction as in
pyruvate dehydrogenase with three enzyme units (cofactors, TPP, Mg2+,
CoA, NAD, FAD, Lipoic acid). NAD+ is an electron acceptor.
NAD+, CoA

25. 5. Succinyl CoA synthetase: Succinyl CoA is a high energy compound like
acetyl CoA with thioester bond. In this reaction, the hydrolysis of the
thioester bond leads to the formation of phosphoester bond with inorganic
phosphate. This phosphate is transferred to histidine residue of the enzyme
and this high energy, unstable phosphate is finally transferred to GDP
resulting in the generation of GTP.
The GTP formed by this reaction may donates its terminal phosphate group
to ADP to form ATP by the reversible action of nucleoside diphospho kinase.

26. 6. Succinate Dehydrogenase: Oxidation of succinate to fumarate. This
is the only citric acid cycle enzyme that is tightly bound to the inner
mitochondrial membrane. It is an FAD dependent enzyme and contents two
iron-sulfur clusters which are thought to carry electrons.
Malonate has similar structure to Succinate, and it competitively inhibits
SDH.

27. 7. Fumarate hydratase (Fumarase): Hydration of fumarate to
malate: It is a highly stereospecific enzyme. The cis form of
fumarate is not recognized by this enzyme.

28. 8. L-Malate dehydrogenase: Oxidation of malate to oxaloacetate: It is
an NAD+ dependent enzyme. Reaction is pulled in forward direction by the
next reaction (citrate synthase reaction) as the oxaloacetate is depleted at
a very fast rate.
NADH + H+

29. Control of the Citric Acid Cycle
1. Synthesis of citrate from oxaloacetate and acetyl CoA
– Negative effector is high levels of ATP
2. Oxidation and decarboxylation of isocitrate to a-
ketoglutarate
– Positive effector, ADP
– Inhibited by high levels of NADH and ATP
3. Conversion of a-ketoglutarate to succinyl CoA
– Inhibited by high concentrations of:
• ATP
• Succinyl CoA
• NADH

30. Conservation of energy in TCA cycle:
The two carbon acetyl group generated in PDC reaction enter into
TCA cycle, and two molecules of CO2 are released in one cycle.
Thus there is complete oxidation of two carbons during one cycle.
Although the two carbons which enter the cycle become the part
of oxaloacetate, and are released as CO2 only in the third round of
the cycle. The energy released due to this oxidation is conserved in
the reduction of 3 NAD+, 1 FAD molecule and synthesis of one
GTP molecule which is converted to ATP.