title: Modulation of the enzymic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase by multiple kinase systems involving reversible phosphorylation: a review.
abstract: 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.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Beg
authors.forename: J A
authors.initials: JA
authors.lastname: Stonik
authors.forename: H B
authors.initials: HB
authors.lastname: Brewer
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008798:Mevalonic Acid / Q000096:biosynthesis; D009097:Multienzyme Complexes / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051381:Rats
chemical_list: D002147:Calmodulin; D009097:Multienzyme Complexes; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases; D008798:Mevalonic Acid; D002118:Calcium