Biochemistry and Molecular Biology - Belyasova N.A. 2002

Metabolism. Processes leading to energy storage
Tricarboxylic acid cycle
Regulation of the TCA cycle

The rate of the TCA cycle is regulated at several levels and is finely tuned to cellular demands. The primary rate-limiting reaction of the cycle is The oxidative decarboxylation of isocitrate. Isocitrate dehydrogenase is an allosteric protein activated by adenosine diphosphate, which increases the enzyme's affinity for its substrates. NADH serves as an inhibitor of isocitrate dehydrogenase activity, "displacing" NAD+ from the Active Site.

Another TCA cycle enzyme, citrate synthase, is inhibited by ATP: as cellular ATP levels rise, the saturation of the enzyme's active site with acetyl-CoA decreases, consequently reducing the rate of citrate formation.

Yet another TCA cycle enzyme, succinate dehydrogenase, modulates its activity through Allosteric Regulation: it is activated by phosphate and succinate, and inhibited by oxaloacetate. When oxaloacetate accumulates in The Cell, succinate oxidation is prevented.

Finally, The activity of alpha-ketoglutarate dehydrogenase is allosterically inhibited by the products of the reaction it catalyzes—succinyl-CoA and NADH.

It should be noted that different organisms may possess various mechanisms for regulating the rate of TCA cycle reactions, including those not described here.



Last update: 06/08/2026

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