S-(N-methylcarbamoyl)glutathione: a reactive S-linked metabolite of methyl isocyanate.
S-(N-methylcarbamoyl)glutathione: a reactive S-linked metabolite of methyl isocyanate.
复制标题
S-(N-甲基氨基甲酰基)谷胱甘肽：异氰酸甲酯的活性 S-连接代谢物。
DOI：
10.1016/0006-291x(90)91937-n
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发表时间：
1990
影响因子：
3.1
通讯作者：
Baillie,TA
中科院分区：
文献类型：
--
作者：
Pearson,PG;Slatter,JG;Rashed,MS;Han,DH;Grillo,MP;Baillie,TA
摘要S-（N-甲基氨基甲酰基）谷胱甘肽是一种具有化学反应活性的谷胱甘肽结合物，已从给予异氰酸甲酯的大鼠胆汁中分离出来，并通过串联质谱法表征为其N-苄氧羰基二甲酯衍生物。这种谷胱甘肽加合物的能力，捐赠的N-甲基氨基甲酰基部分的自由-SH基团的半胱氨酸进行了评价，在体外的帮助下，一个高度特异性的热喷雾LC MS测定程序。谷胱甘肽加合物在缓冲水介质（pH 7.4，37° C）中容易与半胱氨酸反应，2小时后，42.5%的底物以S-（N-甲基氨基甲酰基）半胱氨酸的形式存在。在这些条件下，也容易发生逆反应，即半胱氨酸加合物和游离谷胱甘肽之间的反应。它的结论是，共轭甲基异氰酸酯与谷胱甘肽在体内提供了一个反应性的S-连接的产品，显示出潜在的氨基甲酸酯亲核氨基酸。因此，与动物或人类暴露于异氰酸甲酯相关的各种全身毒性可能是由于异氰酸酯从其谷胱甘肽缀合物中释放出来，因此可以作为异氰酸甲酯在体内运输的媒介物。
Abstract S-(N-methylcarbamoyl) glutathione, a chemically-reactive glutathione conjugate, has been isolated from the bile of rats administered methyl isocyanate and characterized, as its N-benzyloxycarbonyl dimethylester derivative, by tandem mass spectrometry. The ability of this glutathione adduct to donate an N-methylcarbamoyl moiety to the free-SH group of cysteine was evaluated in vitro with the aid of a highly specific thermospray LC MS assay procedure. The glutathione adduct reacted readily with cysteine in buffered aqueous media (pH 7.4, 37° C) and after 2 hr, 42.5% of the substrate existed in the form of S-(N-methylcarbamoyl) cysteine. The reverse reaction, ie between the cysteine adduct and free glutathione, also took place readily under these conditions. It is concluded that conjugation of methyl isocyanate with glutathione in vivo affords a reactive S-linked product which displays the potential to carbamoylate nucleophilic amino acids. The various systemic toxicities associated with exposure of animals or humans to methyl isocyanate could therefore be due to release of the isocyanate from its glutathione conjugate, which thus may serve as a vehicle for the transport of methyl isocyanate in vivo.