Isopentenoid synthesis in isolated embryonic Drosophila cells: absolute mevalonic acid utilization and 3-hydroxy-3-methylglutaryl-coenzyme A reductase modulation.

Isopentenoid synthesis in isolated embryonic Drosophila cells: absolute mevalonic acid utilization and 3-hydroxy-3-methylglutaryl-coenzyme A reductase modulation.
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分离的胚胎果蝇细胞中的类戊烯合成:甲羟戊酸的绝对利用和 3-羟基-3-甲基戊二酰辅酶 A 还原酶调节。

DOI:
10.1016/0003-9861(92)90114-c
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发表时间:
1992
影响因子:
3.9
通讯作者:
Watson,JA
Watson,JA
中科院分区:
生物学3区
文献类型:
--
作者:
Havel,CM;Watson,JA

文献摘要

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The relationship between absolute isopentenoidogenesis (total and specific) and 3-hydroxy-3-methylglutaryl-coenzyme A suppression in response to increased mevalonate availability is unknown. We determinedabsoluteisopentenoidogenesis values for the nonsterologenic Drosophila Kccell incubated (2 h) with increasing [3H]mevalonate concentrations. At least 80% of the maximum suppression of 3-hydroxy-3-methyl glutaryl-coenzyme A activity was achieved when total isopentenoidogenesis was increased only 2-fold. However, a 12-fold increase in total isopentenoidogenesis was achieved at higher exogenous [3H]mevalonate concentrations. Thus, modulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was coupled to physiological changes in mevalonate/nonsterol isopentenoid availability. In contrast, isopentenoid accumulation, oxidation, and secretion were enhanced with pharmacological increases in mevalonate availability. Furthermore, an apparent constancy of total isopentenoidogenesis values plus increased metabolism of exogenous mevalonate and a significant (35–45%) suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, in response to exogenous substrate concentrations (< 150 μm), supported a partial or complete compensatory dimunition in endogenous substrate synthesis. Since these responses occurred within the 2-h study, earlier time periods must be assessed to (i) define theinitialnonsterol-mediated regulatory response and (ii) to trap the nonsterol isopentenoid regulatory signal molecule(s).