Alterations in the rates of synthesis and degradation of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase produced by cholestyramine and mevinolin.
Hepatocytes were prepared from rats previously fed either a normal diet or diets containing cholestyramine or cholestyramine plus mevinolin. The rates of synthesis and degradation of HMG-CoA reductase were determined by immunoprecipitation of the enzyme from cells radiolabeled with [35S]methionine during standard pulse or pulse-chase experiments. In cells prepared from rats fed either a normal diet or a diet supplemented with cholestyramine or cholestyramine plus mevinolin, the relative rates of reductase synthesis were 0.08, 0.21, and 0.99%, respectively, of the rates of total cellular protein synthesis. The corresponding apparent half-lives of the enzyme were approximately 114 min, 153 min, and greater than 10 h. We propose that the elevated reductase activity observed in rats fed cholestyramine and mevinolin (Tanaka, R. D., Edwards, P. A., Lan, S.-F., Knoppel, E. M., and Fogelman, A. M. (1982) J. Lipid Res. 23, 1026-1031) is a result of both increased enzyme synthesis and stabilization of the enzyme. We demonstrate that enzyme stabilization is not an inherent property of the enzyme but is dependent on the presence of mevinolin. We propose that enzyme stabilization results from the decreased cellular levels of some product produced endogenously from mevalonate.
D000818:Animals; D002792:Cholestyramine Resin / Q000494:pharmacology*; D006207:Half-Life; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008148:Lovastatin; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats
D009281:Naphthalenes; D002792:Cholestyramine Resin; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases