Modulation of the enzymic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase by multiple kinase systems involving reversible phosphorylation: a review.

This report summarizes the current concepts regarding the in vitro and in vivo modulation of the enzymic activity of HMG-CoA reductase and mevalonate formation in rat and human liver, as well as in cultured fibroblasts from normal and familial hypercholesterolemic subjects. Three separate mechanisms for the short-term modulation of hepatic HMG-CoA reductase activity by covalent phosphorylation have been described. These mechanisms involved three separate specific kinase systems including reductase kinase, protein kinase C, and a Ca+2, calmodulin-dependent kinase. The conceptual schemes presented in this report will provide a basis for future research as well as an overview for improved understanding of the complex and multifaceted short-term regulation of this key enzyme in the biosynthetic pathways of mevalonate, ubiquinones, dolichols, isopentenyl-tRNAs, and cholesterol.