This document provides information on carbohydrate metabolism and various pathways involved including glycolysis, the citric acid cycle, and pyruvate dehydrogenase complex. It discusses: - The key roles of glucose and glycogen in carbohydrate metabolism - The three phases of glycolysis and production of ATP - Conversion of pyruvate to lactate under anaerobic conditions - Regulation of key enzymes in glycolysis - Significance of glycolysis in various tissues and diseases - The citric acid cycle and its importance in energy production

1. Presented by-
26.Charanjot Singh
27.Dania Kaur
28.Daanishjit Singh
29.Deepinder Kaur
30.Divmehar Kaur

2. Carbohydrates are major sources of energy. They
are first cellular constituents synthesized by green
plants.
Glucose is the central molecule in carbohydrate
metabolism. It is synthesized from non-
carbohydrate precursors and stored as glycogen to
release glucose as and when the need arises.
The normal fasting blood glucose level is 70-100
mg/dL.

3. • Glycolysis
• Inhibitors
• Regulation
• Energetics
• Applied aspect
• PDH Complex
• Regulation
• Biological Importance
• TCA Cycle
• Inhibitors
• Regulation
• Energetics
• Applied aspect

4. Glycolysis is defined as the sequence of reactions
converting glucose to pyruvate or lactate with
production of ATP.

5.  It takes place in all cells of body.
 It is a major pathway for ATP synthesis in
tissues lacking mitochondria. For e.g.-
erythrocytes, cornea, lens etc.
 The enzymes of this pathway are present in
the cytosomal fraction of cell.
 The intermediates of this cycle are useful for
the synthesis of amino acids and fats.

6. There are 3 phases in glycolysis –
 Energy investment phase
 Splitting phase
 Energy Generation phase

8. Under anaerobic conditions, Pyruvate is
reduced by NADH to Lactate in the
presence of enzyme Lactate
Dehydrogenase.
The occurrence of uninterrupted glycolysis
is very essential in skeletal muscle during
strenous exercise where oxygen supply is
very limited.
Glycolysis in erythrocytes leads to lactate
production since mitochondria are absent.

11.  It is a process in which glucose is converted to
lactate in the muscle. In the liver this lactate
is reconverted to glucose.
 Cori cycle basically comes into play to prevent
lactate accumulation in body.
 Lactic acid from the muscle diffuses into
blood. It then reaches liver where it is
oxidised to pyruvate and is diverted to
gluconeogenesis.

14.  Hexokinase - inhibited by glucose-6-phosphate by product
inhibition.
 Phospho fructokinase – It is the most important regulatory
enzyme in glycolysis as it catalyses the rate limiting
commited step . It is an allosteric enzyme regulated by
allosteric effectors.
 ATP,Citrate and hydrogen ions are allosteric inhibitors
 Fructose2,6bisphosphate, ADP, AMP and Pi are allosteric
activators
 Pyruvate Kinase – inhibited by ATP, activated by
fructose1,6bisphosphate. Pyruvate kinase is actve in
dephosphorylated state and inactive in phosphorylated state.
Inactivation of pyruvate kinase by phosphorylation is brought
about by cAMP dependent protein kinase. The hormone
glucagon inhibits hepatic glycolysis by this mechanism.

15.  Glycolysis and dental caries- Dental caries
refers to the decalcification of teeth due to
organic acids released by bacterial infection.
The anaerobic bacteria like streptococcus
mutans , lactobacillus etc colonise the oral
cavity and contribute to development of
caries.
 Low levels of flouride from toothpaste inhibit
the enzyme enolase and reduce glycolysis and
thus tooth decay.

16.  Cancer cells show increased glycolysis. As the
tumours grow rapidly the blood vessels are
unable to supply adequate oxygen and this
leads to hypoxia.
 Lactic acidosis – It is the increase in plasma
lactic acid conc. above 4-15 mg/dL and occurs
due to its increased production. Mild forms of
lactic acidosis are observed post strenous
exercise, low PDH activity, cancers etc.

17.  This is a supplementary pathway to glycolysis which is
operative in erythrocytes. It is concerned with the
synthesis of 2,3 bisphosphoglycerate in RBCs.
 The I,3 bisphosphoglycerate produced in glycolysis is
converted to 2,3 BPG which is hydrolysed to 3-
phosphoglycerate and is ultimately converted to pyruvate
 The production of 2,3 BPG acts as a shunt pathway for
glycolysis to dissipate the energy not needed by RBCs
 The 2,3 BPG produced combines with Hb and reduces its
affinity with oxygen thus causing the unloading of oxygen
into the tissues by oxyHb.
 Increase in erythrocyte 2,3BPG is observed in hypoxic
conditions, high altitude, foetal tissue and anemic
conditions.

19.  Occurs via oxidative decarboxylation .
 Irreversible reaction
 Catalysed by multi enzyme complex- PDH
complex which is found only in the
mitochondria
 High activities of PDH are found in cardiac
muscle and kidney

20.  TPP
 Lipoamide - It contains lipoic acid linked to E
amino group of lysine.
 FAD
 Coenzyme A
 NAD+

23.  It is regulated via end product inhibition- ie by
Acetyl CoA , NADH.
 Besides this PDH is also regulated by
phosphorylation and dephosphorylation mechanism.
PDH is active as a dephospho enzyme and inactive
as a phospho enzyme
 PDH Phosphatase activity is promoted by Ca ,Mg
ions and insulin( in adipose tissue )
 PDH Kinase responsible to form inactive PDH is
promoted by ATP,NADH and Acetyl CoA while it is
inhibited by NAD+, CoA and pyruvate
 Thus high energy signal of NADH and ATP turn off
PDH activity

26.  Lack of TPP due to deficiency of thiamine
inhibits PDH activity causing accumulation of
pyruvate.
 In thiamine deficient alcoholics pyruvate is
rapidly converted to lactate leading to lactic
acidosis.
 In patients with inherited deficiency of PDH
lactic acidosis is observed usually after
glucose load.

27.  Arsenic Poisoning – PDH and alpha keto
glutarate dehydrogenase complex are
inhibited by arsenite. Arsenite binds to Thiol(-
SH) groups of lipoic acid and makes it
unavailable to serve as a cofactor.
 PDH phosphatase activity is promoted by Ca
ions among others . Thus the Ca released
during muscle contraction stimulates PDH and
leads to increased production of energy (by
increasing phosphatase activity)

29.  Also called Citric acid cycle or Krebb Cycle.
 It is the most imp metabolic pathway for the energy
supplied to the body ie 60-70% of ATP is synthesized in
this cycle.
 It essentially involves the oxidation of acetyl coA to
CO2 and water
 It is the final oxidative pathway for carbohydrates,
fats as it provides many intermediates required for
synthesis of amino acid, haem etc.
 Enzymes of the TCA Cycle are located in
mitochondrial matrix close to ETC Chain.

32.  Thiamine (as TPP) acts as a coenzyme for
alpha-keto-glutarate-dehydrogenase.
 Riboflavin as FAD acts as a coenzyme for
succinate dehydrogenase.
 Niacin as NAD acts as an electron acceptor for
isocitrate dehydrogenase, alpha-keto-
glutarate-dehydogenase and malate
dehydrogenase .
Pantothenic acid is attached to active
carboxylic acid residues i.e acetyl coA and
succinyl coA .

33.  It is a suicide substrate
 It is first activated to flouro acetyl coa which
then condenses with oxaloacetate to form
flourocitrate
 TCA cycle is inhibited by flourocitrate though
flouroacetate itself is harmless it is converted
to toxic compound flourocitrate by cellular
metabolism.this is a suicide reaction
committed by the cell.

34.  Citrate synthase is inhibited by ATP, NADH,
Acetyl CoA and succinyl coA
 Isocitrate dehydrogenase is activated by ADP
and inhibited by ATP and NADH.
 Alpha-keto-glutarate-dehydrogenase is
inhibited by succinyl coA , and NADH.
 Availability of ADP also plays an important
role.

37. Amphibolic-because it has both catabolic and
anabolic reactions
The cycle is actively involved in
gluconeogenesis,transamination,deamination.
Anabolic reactions connected with TCA are
1-oxaloacetate and alpha keto glutarate-both
serve as precursors for the synthesis of aspartate
and glutamate which are required for the
synthesis of other non essential amino
acids,purines and pyrimidines.

38. 2-Succinyl CoA is used for the synthesis of
porphyrin and heme.
3-Mitochondria citrate is transported to cytosol
where it is cleaved to provide acetyl coA for
the biosynthesis of fatty acids,sterols etc.