Mevalonolactone inhibits the rate of synthesis and enhances the rate of degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat hepatocytes
- PMID: 6863245
Mevalonolactone inhibits the rate of synthesis and enhances the rate of degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat hepatocytes
Abstract
3-Hydroxy-3-methylglutaryl(HMG)-coenzyme A reductase purified from rat liver in the absence of protease inhibitors is composed of two distinct polypeptides of Mr = 51,000 and 52,500. Antibody raised to enzyme purified from rats fed a diet supplemented with cholestyramine and mevinolin inactivated HMG-CoA reductase. The antibody specifically precipitated a polypeptide of Mr = 94,000 from rat liver cells that had been previously incubated with [35S]methionine. The immunoprecipitation of the 35S-labeled polypeptide of Mr = 94,000 was prevented by addition of unlabeled pure HMG-CoA reductase (Mr = 51,000 and 52,500). Incubation of rat liver cells with mevalonolactone resulted in a decreased activity of HMG-CoA reductase and in a 40% decrease in the rate of incorporation of [35S]methionine into the immunoprecipitable reductase polypeptide of Mr = 94,000. In pulse-chase experiments, mevalonolactone enhanced the rate of degradation of the Mr = 94,000 polypeptide 3-fold. We propose that endogenous microsomal HMG-CoA reductase has a subunit of Mr = 94,000 and that the synthesis and degradation of this polypeptide are regulated by either mevalonolactone or, more likely, a product of mevalonolactone metabolism.
Similar articles
-
In vivo modulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase, reductase kinase, and reductase kinase kinase by mevalonolactone.Proc Natl Acad Sci U S A. 1984 Dec;81(23):7293-7. doi: 10.1073/pnas.81.23.7293. Proc Natl Acad Sci U S A. 1984. PMID: 6594693 Free PMC article.
-
In vivo regulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase: enzyme phosphorylation as an early regulatory response after intragastric administration of mevalonolactone.Proc Natl Acad Sci U S A. 1980 Nov;77(11):6429-33. doi: 10.1073/pnas.77.11.6429. Proc Natl Acad Sci U S A. 1980. PMID: 6256737 Free PMC article.
-
Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin.J Lipid Res. 1988 Jun;29(6):781-96. J Lipid Res. 1988. PMID: 2902179
-
Modulation of rat liver 3-hydroxy-3-methylglutaryl-CoA reductase activity by reversible phosphorylation.Fed Proc. 1982 Aug;41(10):2634-8. Fed Proc. 1982. PMID: 6286363
-
Class II 3-hydroxy-3-methylglutaryl coenzyme A reductases.J Bacteriol. 2004 Apr;186(7):1927-32. doi: 10.1128/JB.186.7.1927-1932.2004. J Bacteriol. 2004. PMID: 15028676 Free PMC article. Review. No abstract available.
Cited by
-
Applications of recombinant DNA technology to studies of metabolic regulation.Biochem J. 1987 Oct 1;247(1):1-13. doi: 10.1042/bj2470001. Biochem J. 1987. PMID: 3318812 Free PMC article. Review. No abstract available.
-
Dislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation.Mol Biol Cell. 2009 Jul;20(14):3330-41. doi: 10.1091/mbc.e08-09-0953. Epub 2009 May 20. Mol Biol Cell. 2009. PMID: 19458199 Free PMC article.
-
A modified radiometric assay for 3-hydroxy-3-methylglutaryl coenzyme A reductase.Lipids. 1984 Dec;19(12):966-70. doi: 10.1007/BF02534735. Lipids. 1984. PMID: 6396479
-
Biogenesis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an integral glycoprotein of the endoplasmic reticulum.Proc Natl Acad Sci U S A. 1984 Mar;81(6):1674-8. doi: 10.1073/pnas.81.6.1674. Proc Natl Acad Sci U S A. 1984. PMID: 6584901 Free PMC article.
-
In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation.Mol Cell Biol. 2001 Jul;21(13):4276-91. doi: 10.1128/MCB.21.13.4276-4291.2001. Mol Cell Biol. 2001. PMID: 11390656 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
