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Succinyl-CoA is a negative regulator of citrate synthase. Explain why this makes sense, and propose a...

Succinyl-CoA is a negative regulator of citrate synthase. Explain why this makes sense, and propose a possible mechanism for how this molecule inhibits citrate synthase. What other step of the citric acid cycle is inhibited by succinyl-CoA, and how do you expect that inhibition mechanism to be similar/different?

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Succinyl-CoA is a negative regulator of citrate synthase and α-ketoglutarate dehydrogenase. Succinyl-CoA inhibits these two enzymes through feedback regulation. Succinyl-CoA is the immediate product of α-ketoglutarate dehydrogenase enzyme but not citrate synthase. Succinyl-CoA competes with acetyl-CoA for citrate synthase (competitive feedback inhibition).

Citrate synthase is one of the key rate-limiting enzymes of TCA cycle and is regulated by succinyl-CoA, oxaloacetate, citrate, NADH.

α-ketoglutarate dehydrogenase can also be inhibited by NADH.

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