title: Isoprenoid synthesis in Halobacterium halobium. Modulation of 3-hydroxy-3-methylglutaryl coenzyme a concentration in response to mevalonate availability.
abstract: Halobacterium halobium was evaluated as a potentially simpler biological model to study the regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity (content) in response to mevalonate availability. H. halobium's HMG-CoA reductase was soluble and required NADPH as its reduced coenzyme. Maximum HMG-CoA reductase activity (4-10 nmol/min/mg of soluble protein) was obtained in buffers which contained 3.5 M KCl. Mevinolin (a) blocked growth of H. halobium, (b) was a competitive inhibitor of HMG-CoA reductase (Ki = 20 nM), (c) did not cause the paradoxical increase in assayable reductase activity, as reported for eukaryotic cells, and (d) caused a rapid (within 30 min) 8-12-fold accumulation of intracellular HMG-CoA. Mevalonate blocked and reversed mevinolin-mediated HMG-CoA accumulation. Although mevinolin-treated cell's growth was restored by mevalonate, HMG-CoA reductase's activity was not. Thus, H. halobium is a unique biological model which allows one to study the regulation of intracellular HMG-CoA concentration and not HMG-CoA reductase activity (content) in response to mevalonate availability.
mesh_terms: D000214:Acyl Coenzyme A / Q000032:analysis / Q000378:metabolism*; D006217:Halobacterium / Q000187:drug effects / Q000378:metabolism*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis; D008148:Lovastatin; D008798:Mevalonic Acid / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology
chemical_list: D000214:Acyl Coenzyme A; D008055:Lipids; D009281:Naphthalenes; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D009249:NADP; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid