Tricarboxylic acid cycle/Krebs (TCA) Cycle / Citric acid cycle

  • TCA is the most important metabolic pathway for the energy supply to the biological system.
  • 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
  • Proposed by Hans Adolf Krebs in 1937.
  • Oxygen consumption in pigeon breast muscle.
  • Nobel Prize 1953.
  • The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids.

Reactions of citric acid cycle

  • Oxidative decarboxylation of pyruvate from glycolysis is link between glycolysis and TCA cycle.
  • Convert pyruvate to acetyl CoA by pyruvate dehydrogenase.

1. Formation of citrate

  • The cycle is starts with condensation of acetyl CoA and oxaloacetate by the enzyme citrate synthase.

2, 3. Formation of Cis-Aconitate and Isocitrate

  • Citrate is isomerized to isocitrate by the enzyme aconitase.
  • Reaction takes place dehydration followed by hydration.

4, 5. Formation of Oxalosuccinate and alpha-Ketoglutarate

  • This reaction achieved by the enzyme isocitrate dehydrogenase (ICD).
  • The formation of NADH and the liberation of CO2 occur at this stage

6. Conversion of alpha-ketoglutarate to succinyl CoA

  • It is occurs through oxidative decarboxylation by the help of catalytic enzyme alpha-ketoglutarate dehydrogenase complex.
  • This enzyme is dependent on five cofactors—TPP, lipoamide, NAD+, FAD and CoA.

7. Formation of succinate

  • Converted succinate by succinate thiokinase with the phosphorylation of GDP to GTP.

8. Conversion of succinate to fumarate

  • Succinate is oxidized by succinate dehydrogenase to fumarate. This reaction results in the production of FADH2.

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.
  • Formatioon of NADH occurs at this stage.
  • The oxaloacetate is regenerated which can combine with another molecule of acetyl CoA, and continue the cycle.

Energetic of citric acid cycle

Hello! My name is Smrutiranjan Dash, a pharmacy professional. belonging from, Bargarh, Odisha. I have acquired Master degree in Pharmacy (Pharmacology) form B.P.U.T, Rourkela, Odisha. Presently I am working as an Assistant Professor at The pharmaceutical college, Barpali.

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