In vivo regulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase: immunotitration of the enzyme after short-term mevalonate or cholesterol feeding.

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Abstract
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-CoA reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] (HMG-CoA reductase), the major regulatory enzyme in cholesterol biosynthesis, is subject to 2 phases of inhibition. The 1st phase of inhibition is explained by in vivo phosphorylation of the enzyme; however, the nature of the 2nd phase of inhibition remained obscure. The present study tested 2 possible explanations for this 2nd 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 immunotimmunotitration of HMG-CoA reductase show that, in short-term studies conducted up to 2 h after the administration of a single dose of mevalonolactone or up to 6 h after a single meal of rat chow containing 2% cholesterol, the in vivo regulation of rat liver HMG-CoA reductase during the 1st half of the dark period does not occur by increased enzyme turnover but, instead, existing enzyme is further inactivated.

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