Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics, Carbohydrate and Lipid Metabolism
Regulation of Carbohydrate Metabolism
Regulation of the Citric Acid Cycle (see Fig. 18.3)

There can be little doubt that in most Tissues where The primary function of The Citric Acid Cycle is energy supply, Respiratory Control—exerted through the functioning of the Cell/36.html">Respiratory Chain and Oxidative Phosphorylation—is the decisive factor in regulating The activity of the cycle. The activity of this cycle is directly tied to the supply of oxidized dehydrogenase Cofactors (such as NAD), which in turn depends on ADP availability and, ultimately, on The rate of ATP consumption. The properties of several Enzymes in this cycle indicate that, In addition to overall regulation, there is also Regulation at the level of the cycle itself. In Brain Cells, where acetyl-CoA is formed predominantly from CARBOHYDRATES, Regulation of the citric acid cycle may occur at the stage catalyzed by Pyruvate dehydrogenase. Within the cycle itself, regulation can be achieved via allosteric inhibition of citrate synthase by ATP or long-chain fatty acyl-CoA derivatives. Mitochondrial NAD-dependent isocitrate dehydrogenase is allosterically activated by ADP and inhibited by ATP and NADH. The $\alpha$-ketoglutarate dehydrogenase complex appears to be regulated similarly to pyruvate dehydrogenase. Succinate dehydrogenase is inhibited by oxaloacetate, and The formation of oxaloacetate in the malate dehydrogenase reaction depends on the [NADH]/[NAD⁺] ratio. Since the $K_\mathfrak{m}$ value of citrate synthase for oxaloacetate is of the same order of magnitude as the intramitochondrial oxaloacetate concentration, the concentration of the latter presumably plays a significant role in regulating the rate of citrate formation. Which of the aforementioned regulatory mechanisms actually function within the cycle in vivo remains unclear.