1. Citric Acid Cycle
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2. Introduction
• Krebs or tricarboxylic acid cycle
• Sequence of reactions in mitochondria that oxidizes the
acetyl moiety of acetyl-CoA to CO2
• Final common pathway for the oxidation of carbohydrate,
lipid, and protein
• Metabolized to acetyl-CoA or intermediates of the cycle
• These processes occur in most tissues, but liver is the only
tissue in which all occur to a significant extent
• Hyperammonemia, as occurs in advanced liver disease,
leads to loss of consciousness, coma, and convulsions as a
result of impaired activity of the citric acid cycle, leading to
reduced formation of ATP
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3. Citric Acid Cycle
• Cycle starts with
reaction between the
acetyl moiety of
acetyl-CoA
• Four-carbon
dicarboxylic acid
oxaloacetate, forming a
six-carbon tricarboxylic
acid, citrate
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4. Citric Acid Cycle
• Main pathway for ATP formation linked to the
oxidation of metabolic fuels
• Process is aerobic, requiring oxygen as the
final oxidant of the reduced coenzymes
• Enzymes of the citric acid cycle are located in
the mitochondrial matrix - either free or
attached to the inner mitochondrial
membrane and the crista membrane
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5. Citric Acid Cycle
• The initial reaction between acetyl-CoA and
oxaloacetate to form citrate is catalyzed by citrate
synthase
• Citrate is isomerized to cis-aconitate by the enzyme
aconitase which is further rehydrated to isocitrate
• Isocitrate undergoes dehydrogenation catalyzed by
isocitrate dehydrogenase to form, initially,
oxalosuccinate, which remains enzyme bound
– NAD to NADH
• It further undergoes decarboxylation to α-
ketoglutarate - requires Mg2+ or Mn2+ ions
– CO2 is given out For more Visit us: www.dentaltutor.in
7. Citric Acid Cycle
• α-Ketoglutarate undergoes oxidative
decarboxylation in a reaction catalyzed by a
multienzyme complex to form Succinyl-CoA
– NAD – NADH, CO2 is given out
• Succinyl-CoA is converted to succinate by the
enzyme succinate thiokinase (succinyl-CoA
synthetase)
– ADP - ATP
• Succinate gets converted to Fumarate in the
presence of succinate dehydrogenase
– FAD - FADH
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9. Citric Acid Cycle
• Fumarate is converted to malate in the
presence of enzyme fumarase
• Malate is again converted to Oxaloacetate in
the presence of enzyme malate
dehydrogenase
– NAD - NADH
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10. VITAMINS PLAY KEY ROLES
IN THE CITRIC ACID CYCLE
• Four of the B-vitamins - essential in the
citric acid cycle.
– Riboflavin: Flavin Adenine Dinucleotide (FAD)
• Cofactor for succinate dehydrogenase
– Niacin: Nicotinamide Adenine Dinucleotide (NAD +),
• Electron acceptor for isocitrate dehydrogenase,
• α-ketoglutarate dehydrogenase
• malate dehydrogenase;
– Thiamin (vitamin B1): Thiamin Diphosphate
• Coenzyme for decarboxylation in the α-ketoglutarate
dehydrogenase reaction;
– Pantothenic acid: part of coenzyme A
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