有机锡对人芳香化酶体外活性的影响。

Effect of organotins on human aromatase activity in vitro.

作者信息

Cooke Gerard M

机构信息

Department of Cellular and Molecular Medicine, Sir Frederick G. Banting Research Center, University of Ottawa, PL 2202D1 Tunney's Pasture, ON, K1A 0L2, Ottawa, Canada.

出版信息

Toxicol Lett. 2002 Jan 25;126(2):121-30. doi: 10.1016/s0378-4274(01)00451-9.

DOI:10.1016/s0378-4274(01)00451-9

PMID:11751016

Abstract

The interaction between the human aromatase enzyme and some organotins was investigated. Tributyltin (TBT) at 12 and 59 microM and dibutyltin at 74 microM inhibited aromatase activity in vitro but monobutyltin and tri-, di- and monooctyltins were without effect. In four separate kinetic studies of aromatase, the K(m(app)) for testosterone was 0.24, 0.21, 0.16 and 0.24 microM. TBT inhibited aromatase activity by causing the K(m(app)) to be increased without affecting the V(max), indicative of competitive inhibition. Slope and intercept replots confirmed the effect of aromatase on the K(m(app)). Slope replots from three separate kinetic studies provided Ki values for TBT of 64.5, 40.9 and 37.3 microM. Consequently, TBT is a competitive inhibitor of human aromatase with a Ki approximately 300-fold the K(m(app)) value.

摘要

对人类芳香化酶与某些有机锡之间的相互作用进行了研究。12微摩尔和59微摩尔的三丁基锡（TBT）以及74微摩尔的二丁基锡在体外抑制了芳香化酶的活性，但单丁基锡以及三辛基锡、二辛基锡和单辛基锡则没有作用。在四项独立的芳香化酶动力学研究中，睾酮的表观米氏常数（K(m(app))）分别为0.24、0.21、0.16和0.24微摩尔。TBT通过使K(m(app))增加而抑制芳香化酶活性，同时不影响最大反应速度（V(max)），这表明是竞争性抑制。斜率和截距重绘图证实了芳香化酶对K(m(app))的影响。来自三项独立动力学研究的斜率重绘图得出TBT的抑制常数（Ki）值分别为64.5、40.9和37.3微摩尔。因此，TBT是人类芳香化酶的竞争性抑制剂，其Ki值约为K(m(app))值的300倍。