Characterization and regulation of HMG-CoA reductase during a cycle of juvenile hormone synthesis.
The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase was characterized in cockroach corpora allata which produce insect juvenile hormone III (methyl-(10R)10,11-epoxy-3,7,11-tri-methyl-2E,6E-dodecadienoate ). HMG-CoA reductase is a microsomal enzyme dependent on NADPH and dithiothreitol (or glutathione) for activity. The enzyme selectively reduced (3S)-HMG-CoA to (3R)-mevalonate with an apparent KM of 7.6 microM. Mevinolin was a competitive inhibitor of HMG-CoA reductase with a KI of 2.4 nM. No evidence for a modulation of enzyme activity by phosphorylation was obtained. Levels of HMG-CoA reductase were not altered after incubation of the corpora allata with either mevinolin (to decrease isoprenoid flux) or with mevalonate or farnesol (to increase isoprenoid flux). Split pairs of corpora allata were used to compare JH III synthetic activity with HMG-CoA reductase activity during the cycle of JH III synthesis that controls vitellogenesis and oocyte growth in adult females. Both activities changed over 10-fold and peaked on day 5 after emergence/mating, but JH III synthesis did not parallel HMG-CoA reductase activity precisely thereafter. The half-life of HMG-CoA reductase measured in the presence of cycloheximide was significantly different between low and high activity glands and was not related to the half-life of JH III synthesis. The results suggest that HMG-CoA reductase should not be considered 'the rate-limiting enzyme' in juvenile hormone synthesis by Diploptera punctata corpora allata.
Feyereisen
R
R
Department of Entomology, Oregon State University, Corvallis 97331.
Farnsworth
D E
DE
D000818:Animals; D003058:Cockroaches; D003335:Corpora Allata / Q000187:drug effects / Q000201:enzymology*; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D005204:Farnesol / Q000494:pharmacology; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D012717:Sesquiterpenes / Q000096:biosynthesis*; D013237:Stereoisomerism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012717:Sesquiterpenes; D005204:Farnesol; C015367:mevalonolactone; D003513:Cycloheximide; D008148:Lovastatin; C036585:juvenile hormone III; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid