Question

Explain the regulation of the allosteric enzyme acetyl-CoA carboxylase by citrate and palmitoyl-CoA.

Answer 1

Ans:

Acetyl CoA carboxylase is a key enzyme for fatty acid biosyntbiosy. This enzyme catalyzes the irreversible conversion of malonyl CoA from acetyl CoA. It is a allosteric enzyme and its activity is regulated by citrate, palmitoyl CoA. Palmitoyl CoA, the final product of fatty acid synthesis act as a negative modulator and citrate act as an allosteric activator of this enzyme. Acetyl CoA is inhibited by phosphorylation. Phosphorylation of the regulatory site decreases the affinity of the enzyme for citrate and in this case high level of citrate are required for activation. Dephosphorylation of the enzyme increases its activity and this dephosphorylation is influenced by insulin/glucagon ratio (insulin signalling leads to dephosphorylation and glucagon signalling leads to phophorylation). When palmitoyl CoA levels in the cell high, Palmitoyl CoA is inhibited acetyl CoA carboxylase activity by feedback inhibition/ end product inhibition. Palmitoyl CoA also inhibits citrate shuttle and slow down fatty acid synthesis.