Regulation of rat liver acetyl-CoA carboxylase. Stimulation of phosphorylation and subsequent inactivation of liver acetyl-CoA carboxylase by cyclic 3':5'-monophosphate and effect on the structure of the enzyme.

The effects of citrate and cyclic AMP on the rate and degree of phosphorylation and inactivation of rat liver acetyl-CoA carboxylase were examined. High citrate concentrations (10 to 20 mM), which are generally used to stabilize and activate the enzyme, inhibit phosphorylation and inactivation of carboxylase. At lower concentrations of citrate, the rate and degree of phosphorylation are increased. Furthermore, phosphorylation and enzyme inactivation are affected by cyclic AMP under these conditions. At high citrate concentrations, cyclic AMP has little or no effect on inactivation and phosphorylation of acetyl-CoA carboxylase. Phosphorlation and inactivation of carboxylase is accompanied by depolymerization of the polymeric form of the enzyme into intermediate and protomeric forms. Depolymerization of carboxylase requires the transfer of the gamma-phosphate group from ATP to carboxylase. Inactivation occurs in the absence of CO2, which indicates that phosphorylation of the enzyme is the cause of inactivation and depolymerization, i.e. carboxylation of the enzyme is not responsible for inactivation of the enzyme.