Regulation of Acetyl-CoA Carboxylase

This chapter discusses the regulation of acetyl-CoA carboxylase, which catalyzes the ATP-dependent carboxYase in the formation of malonyl- coA and is inhibited by long-chain fatty acyl- CoA, and such inhibition is accompanied by enzyme depolymerisation.

Abstract

This chapter discusses the regulation of acetyl-CoA carboxylase. Acetyl-CoA carboxylase catalyzes the ATP-dependent carboxylation of acetyl-CoA in the formation of malonyl-CoA. Malonyl-CoA is then condensed to acetyl-CoA in the process of long-chain fatty acid synthesis. Citrate activation of crude or purified carboxylase is accompanied by polymerization of the enzyme. Various methods of dissociating the high-molecular-weight polymeric form into the protomeric form in vitro result in the inactivation of the carboxylase. Acetyl-CoA carboxylase is inhibited by long-chain fatty acyl-CoA, and such inhibition is accompanied by enzyme depolymerisation. Inactivation of the carboxylase through covalent phosphorylation accompanies depolymerization in the absence of CO2, and this depolymerization occurs even in the presence of citrate. While covalent modification amplifies the sensitivity of the carboxylase toward the allosteric molecules at physiological concentrations, the allosteric molecules in turn affect the covalent modification.