The effect of glucagon on the synthesis and degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase

Abstract

Incubation of rat hepatocytes with glucagon results in a time- and dose-dependent decrease in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. We demonstrate, using immunoprecipitation of radiolabeled enzyme, that 10 nM glucagon inhibits the synthesis of the enzyme by approximately 50%, but that the apparent rate of degradation of the enzyme is not affected by the hormone. We also demonstrate that the intact reductase polypeptide contained phosphoserine. We conclude that glucagon inhibits the activity of the reductase by inhibition of enzyme synthesis.