Reactions of citric acid cycle

Reactions of citric acid cycle

1. Formation of citrate: Krebs cycle proper starts with the condensation of acetyl CoA and oxaloacetate, catalyzed by the enzyme citrate synthase.

2. and 3. Citrate is isomerized to isocitrate by the enzyme aconitase.

  • This is achieved in a two-stage reaction of dehydration followed by

  • hydration through the formation of an intermediate—cis-aconitate.

4. and 5. Formation of alpha-ketoglutarate : The enzyme isocitrate dehydrogenase (ICD) catalyses the conversion (oxidative decarboxylation) of isocitrate to oxalosuccinate and then to -ketoglutarate. The formation of NADH and the liberation of CO2 occur at this stage.

6. Conversion of alpha-ketoglutarate to succinyl CoA occurs through oxidative decarboxylation, catalysed by alpha-ketoglutarate dehydrogenase complex.

  • This enzyme is dependent on five cofactors—TPP, lipoamide, NAD+, FAD and CoA.

7. Formation of succinate : Succinyl CoA is converted to succinate by succinate thiokinase.

  • This reaction is coupled with the phosphorylation of GDP to GTP.

  • This is a substrate-level phosphorylation.

8. Conversion of succinate to fumarate: Succinate is oxidized by succinate dehydrogenase to fumarate.

  • This reaction results in the production of FADH2 and not NADH.

9. Formation of malate: The enzyme fumarase catalyzes 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.

  • The third and final synthesis of NADH occurs at this stage.

  • Energetics of citric acid cycle

  • During the process of oxidation of acetyl CoA via citric acid cycle, 4 reducing equivalents (3 as NADH and one as FADH2) are produced.

  • Oxidation of 3 NADH by electron transport chain coupled with oxidative phosphorylation results in the synthesis of 9 ATP, whereas FADH2 leads to the formation of 2 ATP.

  • Besides, there is one substrate level phosphorylation.


Thus, a total of 12 ATP (10 as per recent evidence) are produced from one acetyl CoA

Inhibitors of Krebs cycle

The important enzymes of the TCA cycle inhibited by the respective inhibitors are listed