REACTIONS OF NITROSOBENZENE WITH REDUCED GLUTATHIONE
REACTIONS OF NITROSOBENZENE WITH REDUCED GLUTATHIONE
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DOI：
10.1016/0009-2797(79)90011-5
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发表时间：
1979-01-01
影响因子：
5.1
通讯作者：
EYER, P
中科院分区：
文献类型：
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作者：
EYER, P
致癌物亚硝基苯 (NOB) 与[人]红细胞内的还原型谷胱甘肽 (GSH) 和血红蛋白形成酸不稳定结合物。在体外，NOB 与 GSH 快速反应，形成苯羟胺 (PH)、氧化型谷胱甘肽 (GSSG) 和一种被称为谷胱甘肽亚磺酰苯胺 (GSO-AN) 的水溶性化合物。未检测到游离苯胺（AN）、氨基酚和偶氮苯。形成的 PH 比例随着 GSH 浓度的增加和 pH 值的升高而增加。光谱分析揭示了在二级反应之后形成不稳定加合物(K = 5×103M-1.cntdot.sec -1，在pH 7.4和37℃)。该反应是可逆的，因为几乎所有的 NOB 都可以用乙醚从不稳定的中间体中萃取出来。不稳定的中间体被转化为 GSO-AN（在较低 pH 值下速率增加），或者被 GSH 裂解，形成 GSSG 和 PH。通过平衡数据的分析排除了NOB和硫醇自由基的中间形成。针对所提出的反应机理提出了一个初步方案。
The carcinogen nitrosobenzene (NOB) formed acid labile conjugates with reduced glutathione (GSH) and Hb within [human] red cells. In vitro, NOB rapidly reacted with GSH with formation of phenylhydroxylamine (PH), oxidized glutathione (GSSG), and a water-soluble compound identified as glutathionesulfinanilide (GSO-AN). Free aniline (AN), aminophenols and azoxybenzene were not detected. The proportion of PH formed increased with increasing GSH concentration and at higher pH values. Spectroscopic analysis revealed the formation of a labile adduct following a 2nd order reaction (K = 5 .times. 103 M-1 .cntdot. sec -1 at pH 7.4 and 37.degree. C). This reaction was reversible because nearly all NOB could be extracted with ether from the labile intermediate. The labile intermediate was transformed into GSO-AN (with increasing rate at lower pH values) or it was cleaved by GSH with formation of GSSG and PH. Intermediate formation of NOB and thiol radicals was ruled out by analysis of the equilibrium data. A tentative scheme is presented for the proposed reaction mechanism.