DETERMINATION OF THE RELATIVE CONTRIBUTIONS OF THE DISELENIDE AND SELENOL FORMS OF EBSELEN IN THE MECHANISM OF ITS GLUTATHIONE PEROXIDASE-LIKE ACTIVITY

被引:71
作者
MORGENSTERN, R
COTGREAVE, IA
ENGMAN, L
机构
[1] KAROLINSKA INST,DEPT TOXICOL,S-10401 STOCKHOLM 60,SWEDEN
[2] ROYAL INST TECHNOL,DEPT ORGAN CHEM,S-10044 STOCKHOLM 70,SWEDEN
关键词
EBSELEN; EBSELEN SELENOL; EBSELEN DISELENIDE; GLUTATHIONE; PEROXIDASE; CATALYTIC MECHANISM;
D O I
10.1016/0009-2797(92)90122-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The molecular basis of the glutathione peroxidase activity of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) was investigated by the use of synthesised, authentic intermediates identical to those formed by the reaction of ebselen with glutathione. The second order rate constants for the reaction of ebselen (0.29 mM-1 min-1), ebselen-glutathione selenosulfide (less-than-or-equal-to 0.01 mM-1 min-1), ebselen selenol (2.8 mM-1 min-1) and ebselen diselenide (0.32 mM-1 min-1) with hydrogen peroxide reveal that the selenol is particularly active in this respect. The determination of the relative amounts of ebselen selenol and diselenide under typical peroxidase assay conditions implies that the selenol is the predominant molecular species responsible for the glutathione - (70%) - and dithiothreitol - (96%) - dependent peroxidase activity of ebselen.
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页码:77 / 84
页数:8
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