In vivo regulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase: immunotitration of the enzyme after short-term mevalonate or cholesterol feeding.
In recent studies using either a single dose of mevalonolactone administered by intragastric tube or a single meal containing 2% cholesterol, it was demonstrated that rat liver hydroxymethylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] (HMG-CoA reductase) the major regulatory enzyme in cholesterol biosynthesis, is subject to two phases of inhibition. The first phase of inhibition is explained by in vivo phosphorylation of the enzyme; however, the nature of the second phase of inhibition remained obscure. The present study tested two possible explanations for this second phase of inhibition--increased enzyme turnover leading to a decreased concentration of HMG-CoA reductase molecules, and further inactivation of existing enzyme molecules. The results with the technique of immunotitration of HMG-CoA reductase show that, in short-term studies conducted up to 2 hr after the administration of a single dose of mevalonolactone or up to 6 hr after a single meal of rat chow containing 2% cholesterol, the in vivo regulation of rat liver HMG-CoA reductase during the first half of the dark period does not occur by increased enzyme turnover but, instead, existing enzyme is further inactivated.
D000818:Animals; D000936:Antigen-Antibody Complex; D002784:Cholesterol / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007106:Immune Sera; D007123:Immunoelectrophoresis, Two-Dimensional; D007700:Kinetics; D008297:Male; D008798:Mevalonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D000936:Antigen-Antibody Complex; D007106:Immune Sera; C015367:mevalonolactone; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid