Pyruvate Dehydrogenase Complex Regulation

The pyruvate dehydrogenase complex is subject to both allosteric and (in mammals) covalent regulation (Figure 14.16).

> E2 of the pyruvate dehydrogenase complex (the transacetylase component) is inhibited by acetyl-CoA and activated by CoASH. Thus, the activity of the pyruvate dehydrogenase complex is coordinated with the ratio of acetylated to free coenzyme A.

> E3 (the dihydrolipoamide dehydrogenase component) is inhibited by NADH and activated by NAD+. Thus, the activity of the complex is coordinated with the [NAD+]/[NADH] ratio, too.

> ATP is an allosteric inhibitor of the complex.

> AMP is an allosteric activator of the complex.

> In mammals, E1 of the pyruvate dehydrogenase complex is susceptible to covalent modification (Figure 14.17).

> > Phosphorylation of E1 by ATP and pyruvate dehydrogenase kinase inactivates it. Pyruvate dehydrogenase kinase is activated, in turn, by NADH and acetyl-CoA.

> > Dephosphorylation of E1 is catalyzed by pyruvate dehydrogenase phosphatase (activates it). Pyruvate dehydrogenase phosphatase is activated, in turn, by Ca2+ and Mg2+.

Note that Mg2+ concentration increases as ATP is converted to ADP and decreases with the reverse reaction. This means that activation of the pyruvate dehydrogenase complex is susceptible to the levels of ADP/ATP (i.e., the energy charge).

See also: Pyruvate Oxidation