CHARACTERIZATION AND REGULATION OF HMG-COA REDUCTASE DURING A CYCLE OF JUVENILE-HORMONE SYNTHESIS

CHARACTERIZATION AND REGULATION OF HMG-COA REDUCTASE DURING A CYCLE OF JUVENILE-HORMONE SYNTHESIS
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DOI:
10.1016/0303-7207(87)90178-x
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发表时间:
1987-10-01
影响因子:
4.1
通讯作者:
FARNSWORTH, DE
FARNSWORTH, DE
中科院分区:
医学2区
文献类型:
--
作者:
FEYEREISEN, R;FARNSWORTH, DE

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3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶在产生昆虫保幼激素III(methyl-(10R)10,11-epoxy-3,7,11-trimethyl-2E,6E-dodecadienoate).的蟑螂鼻小体中的特性HMG-CoA还原酶是一种依赖于NADPH和二硫苏糖醇(或谷胱甘肽)的微粒体酶。该酶选择性地将(3S)-HMG-CoA还原为(3R)-甲戊酸,表观Km值为7.6um。Mevinolin是HMG-CoA还原酶的竞争性抑制剂,K1值为2.4 nM。没有证据表明磷酸化对酶活性有调节作用。甲氧戊酸或法尼醇(增加异戊二烯流量)与甲氧诺林(减少异戊二烯流量)孵育后,HMG-CoA还原酶的水平没有改变。在控制成年雌性卵黄发生和卵母细胞生长的JH III合成周期中,对JH III合成活性与HMG-CoA还原酶活性进行比较。两种酶的活性变化均超过10倍,并在羽化/交配后第5天达到峰值,但JH III的合成并不恰好在此后与HMG-CoA还原酶的活性平行。在环己亚胺存在下测得的HMG-CoA还原酶半衰期在低活性腺体和高活性腺体之间有显著差异,与JH III合成的半衰期无关。这些结果表明,HMG-CoA还原酶不应被认为是斑纹夜蛾保幼激素合成的“限速酶”。
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-trimethyl-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 .mu.M. Mevinolin was a competitive inhibitor of HMG-CoA reductase with a K1 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 comapre 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 tht HMG-CoA reductase should not be considered ''the rate-limiting enzyme'' in juvenile hormone synthesis by Diploptera punctata corpora allata.