Citric Acid Cycle

BioFiles 2007, 2.6, 16.

BioFiles 2007, 2.6, 16.

Acetyl-CoA enters a cycle whose discovery by Hans Krebs 70 years ago marked a milestone in biochemistry. The citric acid cycle is also termed the tricarboxylic acid cycle, TCA cycle or Krebs cycle (see Figure 3).



Figure 3. Citric Acid Cycle.


It is started by an enzymatic aldol addition reaction of acetyl CoA to oxaloacetate (1) forming citrate (2), which is then isomerized by a dehydration-hydration sequence to yield (2R,3S)-isocitrate (3).

Further enzymatic oxidation and decarboxylation gives 2- ketoglutarate (4), which, after another enzymatic decarboxylation and oxidation is, transformed into succinyl-CoA (5). The hydrolysis of this metabolite to succinate (6) is coupled to the phosphorylation of GDP to GTP.

Enzymatic desaturation by FAD-dependent succinate dehydrogenase yields fumarate (7), which, after stereospecific hydration catalyzed by fumarase is, transformed to L-malate (8).

The last step of NAD-coupled oxidation of L-malate (8) to oxaloacetate (1) is catalyzed by malate dehydrogenase and closes the cycle.

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