Mevalonolactone inhibits the rate of synthesis and enhances the rate of degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat hepatocytes.

摘要: 3-Hydroxy-3-methylglutaryl(HMG)-coenzyme A reductase purified from rat liver in the absence of protease inhibitors is composed two distinct polypeptides Mr = 51,000 and 52,500. Antibody raised to enzyme rats fed a diet supplemented with cholestyramine mevinolin inactivated HMG-CoA reductase. The antibody specifically precipitated polypeptide 94,000 cells that had been previously incubated [35S]methionine. immunoprecipitation 35S-labeled was prevented by addition unlabeled pure (Mr 52,500). Incubation mevalonolactone resulted decreased activity 40% decrease rate incorporation [35S]methionine into immunoprecipitable 94,000. In pulse-chase experiments, enhanced degradation 3-fold. We propose endogenous microsomal has subunit synthesis this are regulated either or, more likely, product metabolism.