title: Inhibition of a plant sesquiterpene cyclase by mevinolin.
abstract: The specificity of mevinolin as an inhibitor of sterol and sesquiterpene metabolism in tobacco cell suspension cultures was examined. Exogenous mevinolin inhibited [14C]acetate, but not [3H]mevalonate incorporation into free sterols. In contrast, mevinolin inhibited the incorporation of both [14C]acetate and [3H]mevalonate into capsidiol, an extracellular sesquiterpene. Microsomal 3-hydroxy-3-methylglutaryl Coenzyme A reductase was inhibited greater than 90% by microM mevinolin, while squalene synthetase was insensitive to even 600 microM mevinolin. Sesquiterpene cyclase, the first branch point enzyme specific for sesquiterpene biosynthesis, was inhibited in a dose-dependent manner by mevinolin with a 50% reduction in activity at 100 microM. Kinetic analysis indicated that the mechanism for inhibition was complex with mevinolin acting as both a competitive and noncompetitive inhibitor. The results suggest that the mevinolin inhibition of [3H]mevalonate incorporation into extracellular sesquiterpenes can, in part, be attributed to a secondary, but specific, site of inhibition, the sesquiterpene cyclase.
authors.affiliation: Agronomy Department, University of Kentucky, Lexington, 40546-0091.
authors.forename: U
authors.initials: U
authors.lastname: Vögeli
authors.forename: J
authors.initials: J
authors.lastname: Chappell
mesh_terms: D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019753:Intramolecular Lyases; D007535:Isomerases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000378:metabolism; D010944:Plants / Q000378:metabolism*; D012717:Sesquiterpenes / Q000378:metabolism
chemical_list: D000085:Acetates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012717:Sesquiterpenes; D008148:Lovastatin; D007535:Isomerases; D019753:Intramolecular Lyases; C048278:farnesylpyrophosphate cyclase; D019342:Acetic Acid; D008798:Mevalonic Acid