MECHANISM OF GLUCAGON-INHIBITION OF LIVER ACETYL-COA CARBOXYLASE - INTERRELATIONSHIP OF THE EFFECTS OF PHOSPHORYLATION, POLYMER-PROTOMER TRANSITION, AND CITRATE ON ENZYME-ACTIVITY

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 260  (6) , 3791-3797
Abstract
The short-term regulation of rat liver acetyl-CoA carboxylase by glucagon was studied in hepatocytes from rats that were fasted and refed a fat-free diet. Glucagon inhibition of the activity of this enzyme can be accounted for by a direct correlation between phosphorylation, polymer-protomer ratio and activity. Glucagon rapidly inactivates acetyl-CoA carboxylase with an accompanying 4-fold increase in the phosphorylation of the enzyme and 3-fold increase in the protomer-polymer ratio of enzyme protein. Citrate, an allosteric activator of acetyl-CoA carboxylase required for enzyme activity, has no effect on these phenomena, indicating a mechanism that is independent of citrate concentration within the cell. The observation of these effects of glucagon on acetyl-CoA carboxylase activity is absolutely dependent upon the minimization of proteolytic degradation of the enzyme after cell lysis. Therefore, for the 1st time, an interrelationship was demonstrated between phosphorylation, protomer-polymer ratio and citrate for the inactivation of acetyl-CoA carboxylase by glucagon.