citric acid cycle

Citric Acid CycleDr. Deepak K. Gupta

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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 aresult of impaired activity of the citric acid cycle, leading toreduced formation of ATP


Citric Acid Cycle

• Cycle starts with reaction between the acetyl moiety ofacetyl-CoA

• Four-carbon dicarboxylic acid oxaloacetate, forming a six-carbon tricarboxylicacid, citrate


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


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


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-CoAsynthetase)– ADP - ATP

• Succinate gets converted to Fumarate in the presence of succinate dehydrogenase– FAD - FADH


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 malatedehydrogenase

– NAD - NADH


VITAMINS PLAY KEY ROLESIN THE CITRIC ACID CYCLE

• Four of the B-vitamins - essential in thecitric 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


References

• Color_Atlas_of_Biochemistry_2005

• Harpers_Biochemistry_26th_ed

• Lehninger Principles of Biochemistry, Fourth Edition - David L. Nelson, Michael M. Cox.

• Biochemistry – U. Satyanarayan, U. Chakerpeni


citric acid cycle

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