KE7001 Biochemistry Lectures

The citric acid cycle

Reading material: Stryer, Chapter 17

Abstract: Pyruvate, the end product of glycolysis, undergoes dehydrogenation and decarboxylation by the pyruvate dehydrogenase complex, which contains three sequentially acting enzymes and requires five coenzymes, to yield acetyl-CoA and CO₂. Acetyl-CoA (a two carbon unit) enters the citric acid cycle, which occurs in the mitochondria of eucaryotes. The enzyme citrate synthase catalyses the condensation of acetyl-CoA with oxaloacetate (a four carbon unit) to form citrate. Isocitrate is formed which is further oxidised to alpha-ketoglutarate by isocitrate dehydrogenase in a reaction that also yields CO₂. Alpha-ketoglutarate then undergoes dehydrogenation and decarboxylation to succinyl-CoA and CO₂. Succinyl-CoA reacts with GDP and P_i to form free succinate and GTP. Succinate is then oxidised to fumarate by succinate dehydrogenase which is further oxidised to malate by NAD-linked malate dehydrogenase to regenerate a molecule of oxaloacetate.

The overall rate of the cycle is controlled by the rate of conversion of pyruvate to acetyl-CoA and by the flux through two enzymes of the cycle: isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase. The end products ATP and NADH are inhibitory.

Citric acid cycle intermediates are also used as precursors in biosynthesis of amino acids and other biomolecules.

The Glyoxylate cycle: Many bacteria and plants can use acetate or other compounds that yield acetyl-CoA as the only substrate for surviving. Instead of being decarboxylated, isocitrate is cleaved into succinate and glyoxylate. Succinate can thereby be used for glucose synthesis.

Links:
Stryer: Chapter 17 Living figures (Use Netscape/Chime)

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