In: Chemistry
A) the rate of the cycle is reduced when the cell has a high level of ATP.
The citric acid cycle is regulated primarily by the concentration of ATP and NADH. The key control points are the enzymes isocitrate dehydrogenase and α-ketoglutarate dehydrogenase.
Isocitrate dehydrogenase is allosterically stimulated by ADP, which enhances the enzyme's affinity for substrates. The binding of isocitrate, NAD+, Mg2+, and ADP is mutually cooperative. In contrast, NADH inhibits iso-citrate dehydrogenase by directly displacing NAD+. ATP, too, is inhibitory. It is important to note that several steps in the cycle require NAD+ or FAD, which are abundant only when the energy charge is low.
A second control site in the citric acid cycle is α-ketoglutarate dehydrogenase. Some aspects of this enzyme's control are like those of the pyruvate dehydrogenase complex, as might be expected from the homology of the two enzymes. α-Ketoglutarate dehydrogenase is inhibited by succinyl CoA and NADH, the products of the reaction that it catalyzes. In addition, α-ketoglutarate dehydrogenase is inhibited by a high energy charge. Thus, the rate of the cycle is reduced when the cell has a high level of ATP.