- 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