Reactivity, allosteric regulation

The activity of pyruvate dehydrogenase is regulated by two mechanisms product inhibition and covalent modification (Section 6.5). The enzyme complex is allosterically activated by NAD+, CoASH, and AMP. It is inhibited by high concentrations of ATP and the reaction products acetyl-CoA and NADH. In vertebrates these molecules also activate a kinase, which converts the active pyruvate dehydrogenase complex to an inactive phosphorylated form. High concentrations of the substrates pyruvate, CoASH, and NAD+ inhibit the activity of the kinase. The pyruvate dehydrogenase complex is reactivated by a dephosphorylation reaction catalyzed by a phosphoprotein phosphatase. The phosphoprotein phosphatase is activated when the mitochondrial ATP concentration is low. 

In conclusion, the PR studies of the cd NiRs provide a clear example of an allosteric control mechanism of intraprotein ET reactivity this system is an attractive model for internal control of charge migration and distribution in proteins. The immediate candidate for observation of similar regulation is in one of nature s key players in biological energy conversion, namely, cytochrome c oxidase, which will be discussed later (cf. Section Vl.A). 

The regulation of enzyme action and function can be accomplished by allosteric effects. The binding of an effector at an allosteric site can induce conformational changes at an active site and alter the reactivity of an enzyme towards its substrate. This feature of enzymic catalysis should be capable of imitation in simpler synthetic systems. 

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