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镉对大鼠肝微粒体中环氧苯乙烯和苯并(a)芘-4,5-氧化物水化作用的抑制动力学

Kinetics of the inhibition of styrene oxide and benzo(a)pyrene-4,5-oxide hydration in rat liver microsomes by cadmium.

作者信息

Parkki M G, Aitio A, Bend J R

出版信息

Biochim Biophys Acta. 1980 Aug 7;614(2):625-8. doi: 10.1016/0005-2744(80)90252-1.

Abstract

The kinetics of the inhibition by cadmium of styrene oxide and benzo(a)pyrene-4,5-oxide hydration were studied in a microsomal preparation from rat liver. Cadmium inhibited the hydration of styrene oxide in an apparently noncompetitive manner, whereas the inhibition of benzo(a)pyrene-4,5-oxide hydration showed a competitive mechanism. Styrene oxide inhibited the hydration of benzo(a)pyrene-4,5-oxide competitively and cyclohexene oxide inhibited the hydration of both styrene oxide and benzo(a)pyrene-4,5-oxide competitively. The present data suggest that cadmium is bound near the active centre of the enzyme. Occupation of this site by cadmium inhibits the enzymic hydration of the polycyclic benzo(a)pyrene-4,5-oxide molecule competitively, and that of the smaller monocyclic alkene oxide of styrene noncompetitively. The estimated Ki values were below 10 mu mol for hydration of both substrates indicating that cadmium is a very potent inhibitor of epoxide hydration.

摘要

在大鼠肝脏微粒体制剂中研究了镉对环氧苯乙烯和苯并(a)芘-4,5-氧化物水化作用的抑制动力学。镉以明显的非竞争性方式抑制环氧苯乙烯的水化作用,而对苯并(a)芘-4,5-氧化物水化作用的抑制呈现竞争性机制。环氧苯乙烯竞争性抑制苯并(a)芘-4,5-氧化物的水化作用,氧化环己烯竞争性抑制环氧苯乙烯和苯并(a)芘-4,5-氧化物两者的水化作用。目前的数据表明,镉结合在酶的活性中心附近。镉占据该位点竞争性抑制多环苯并(a)芘-4,5-氧化物分子的酶促水化作用,非竞争性抑制较小的单环环氧烯烃苯乙烯的水化作用。两种底物水化作用的估计Ki值均低于10 μmol,表明镉是环氧水化作用的一种非常有效的抑制剂。

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