A METABOLITE OF ACETAMINOPHEN COVALENTLY BINDS TO THE 56-KDA SELENIUM BINDING-PROTEIN

被引：94

作者：

PUMFORD, NR ^{[1
]}

MARTIN, BM ^{[1
]}

HINSON, JA ^{[1
]}

机构：

[1] NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1992年 / 182卷 / 03期

关键词：

D O I：

10.1016/0006-291X(92)91881-P

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：

Acetaminophen is metabolized by cytochrome P450 to a reactive metabolite that covalently binds to proteins and this binding correlates with the hepatotoxicity. The major protein adduct was previously reported to be a 55 kDa protein that was detected on Western blots using antisera specific for 3-(cystein-S-yl)acetaminophen. In this study, the 55 kDa protein was isolated using a combination of ion exchange fast flow chromatography, hydroxyapatite HPLC and anion exchange HPLC. Amino acid sequences of 8 internal peptides from a trypsin digestion of the 55 kDa protein were found to have 97% homology with the deduced amino acid sequence from a cDNA that corresponds to a 56 kDa selenium binding protein. This is the first report of a specific protein to which a metabolite of acetaminophen covalently binds. © 1992.

引用

页码：1348 / 1355

页数：8