- Sir Hans Krebs, an English biochemist, described a mechanism in 1937 that included a series of chemical events that acetyl
- Because CoA is transformed into carbon dioxide and water, the cycle is known as Kreb’s cycle.
- In contrast to glycolysis, where the enzymes catalyse the processes in the cytosol, all of the enzymes for this cycle are found inside mitochondria (mitochondrial matrix).
- Before pyruvate can enter the citric acid cycle, it must be oxidatively decarboxylated to acetyl CoA (active acetate).
- Three different enzymes working sequentially in a multienzyme complex catalyse this reaction .
- This formation of acetyl CoA from pyruvate by alpha-oxidative decarboxylation occurs in the mitochondrion following the formation of pyruvate in the cytosol during glycolysis.
- The reaction involves six cofactors: coenzyme A, NAD+, lipoic acid, FAD, thiamine pyrophosphate (TPP) and Mg2+.
TPP, FAD
CH3-CO-COOH+CoASH+NAD+ → CH3-CO-S-CoA+NADH+H++CO2 Lipoate, Mg2
Acetyl CoA, derived mainly from the oxidation of carbohydrates, lipids and proteins, combines with oxaloacetate to form citrate which is the first reaction of the citric acid cycle.Subsequently, citrate is oxidised in a series of reactions liberating carbon dioxide and reducing equivalents (NADH, FADH2). The oxaloacetate is regenerated and functions therefore in a catalytic manner in the oxidation of acetyl CoA to two molecules of carbon dioxide.
Significance
- As glucose, fatty acids, and many amino acids are all converted to acetyl CoA through the citric acid cycle, it serves as the final common mechanism for the oxidation of carbohydrates, lipids, and proteins.
- A large portion of the free energy released during the oxidation of carbohydrates, lipids, and amino acids is made accessible through this cycle.
- The TCA cycle is also significant because it has a dual or amphibolic function in the creation of other biomolecules such amino acids, fatty acids, and glucose.