CAC, discovered by Sir Hans Krebs in 1937, is a metabolic process by which
electron carriers such as the coenzyme NADH and the cofactor FADH2
are produced for oxidation and energy yield, and produces energy in the form of
GTP which is readily converted into ATP using nucleoside-diphosphate kinase.
Intermediates in the cycle can be either completely oxidised to CO2
and H2O, or starting as precursors for biosynthetic pathways.
The CAC consists of 8 enzyme-controlled steps: Citrate synthase
catalyses the condensation of acetyl CoA, the 2-carbon product of glycolysis,
with oxaloacetate, a 4-carbon CAC intermediate, to produce citrate, a 6-carbon intermediate.
Aconitase catalyses the two-step sequential dehydration and hydration of
citrate to isocitrate, another 6-carbon intermediate. Isocitrate dehydrogenase
catalyses the two-step oxidative decarboxylation of isocitrate to
?-ketoglutarate, a 5-carbon intermediate. The first reaction is accompanied by
the reduction of NAD+ to NADH and the second reaction involves the
elimination of a carboxylate group as carbon dioxide. ?-ketoglutarate
dehydrogenase catalyses the oxidative decarboxylation of ?-ketoglutarate to
succinyl-CoA, a 4-carbon intermediate. This reaction is also accompanied by the
reduction of NAD+ to NADH and the elimination of a carboxylate group
as carbon dioxide. Succinyl-CoA synthetase catalyses the substrate-level
phosphorylation of succinyl-CoA to succinate, another 4-carbon intermediate.
This is accompanied by the phosphorylation of ADP to ATP. Succinate
dehydrogenase catalyses the dehydrogenation of succinate to fumarate, another
4-cabon intermediate. This is facilitated by the reduction of FAD to FH2
and the elimination of CoA. Fumarase catalyses the hydration of fumarate to
malate, another 4-carbon intermediate. Malate dehydrogenase catalyses the
dehydrogenation of malate to oxaloacetate. This is accompanied with the
reduction of NAD+ to NADH.
In summary, for every molecule of acetyl-CoA; two molecules of
carbon dioxide are released, substrate-level phosphorylation produces one GDP
and four reduced cofactor molecules.