Question

Name one competitive inhibitor involved in tca cycle

Answer 1

 we saw earlier, glucose can be formed from pyruvate (Section 16.3). However, the formation of acetyl CoA from pyruvate is an irreversible step in animals and thus they are unable to convert acetyl CoA back into glucose. The oxidative decarboxylation of pyruvate to acetyl CoA commits the carbon atoms of glucose to two principal fates: oxidation to CO2 by the citric acid cycle, with the concomitant generation of energy, or incorporation into lipid (Figure 17.16). As expected of an enzyme at a critical branch point in metabolism, the activity of the pyruvate dehydrogenase complex is stringently controlled by several means (Figure 17.17). High concentrations of reaction products of the complex inhibit the reaction: acetyl CoA inhibits the transacetylase component (E2), whereas NADH inhibits the dihydrolipoyl dehydrogenase (E3). However, the key means of regulation in eukaryotes is covalent modification of the pyruvate dehydrogenase component. Phos-phorylation of the pyruvate dehydrogenase component (E1) by a specific kinase switches off the activity of the complex. Deactivation is reversed by the action of a specific phosphatase. The site of phosphorylation is the transacetylase component (E2), again highlighting the structural and mechanistic importance of this core. Increasing the NADH/NAD+, acetyl CoA/CoA, or ATP/ADPratio promotes phosphorylation and, hence, deactivation of the complex. In other words, high concentrations of immediate (acetyl CoA and NADH) and ultimate (ATP) products inhibit the activity. Thus, pyruvate dehydrogenase is switched off when the energy charge is high and biosynthetic intermediates are abundant. On the other hand, pyruvate as well as ADP (a signal of low energy charge) activate the dehydrogenase by inhibiting the kinase.