CHARACTERIZATION OF ETHANOL-INDUCIBLE HUMAN-LIVER N-NITROSODIMETHYLAMINE DEMETHYLASE
CHARACTERIZATION OF ETHANOL-INDUCIBLE HUMAN-LIVER N-NITROSODIMETHYLAMINE DEMETHYLASE
复制标题
DOI：
10.1021/bi00370a001
复制
发表时间：
1986-11-04
期刊：
影响因子：
2.9
通讯作者：
GUZELIAN, PS
中科院分区：
文献类型：
--
作者：
WRIGHTON, SA;THOMAS, PE;GUZELIAN, PS
通过使用针对肝细胞色素 P-450j（一种在用乙醇或异烟肼处理的大鼠中诱导的酶）的单特异性抗体，我们从人肝脏中纯化了相关的细胞色素 P-450，称为 HLj。 HLj 的 NH2 末端氨基酸序列类似于大鼠 P-450j 和 P-450 LM3a（兔肝中的同源细胞色素），在两名乙醇中毒患者和一名服用异烟肼患者制备的肝微粒体样本中浓度最高，并催化原致癌物 N-亚硝基二甲胺的代谢激活。此外，9 个人类肝脏 RNA 样本中的每一个都含有一种可与克隆的 HLj cDNA 杂交的 mRNA。我们得出的结论是，HLj 在结构、功能和一些调控特征方面与大鼠 P-450j 和兔 P-450 LM3a 相关，细胞色素对几种临床相关细胞毒性和致癌药物的代谢至关重要。
Through the use of monospecific antibodies directed against hepatic cytochrome P-450j, an enzyme induced in rats treated with ethanol or isoniazid, we have purified from human liver the related cytochrome P-450 termed HLj. HLj resembles rat P-450j and P-450 LM3a, the homologous cytochrome in rabbit liver, in its NH2-terminal amino acid sequence, in being in highest concentration in liver microsome samples prepared from two patients intoxicated by ethanol and one patient given isoniazid, and in catalyzing the metabolic activation of the procarcinogen N-nitrosodimethylamine. Furthermore, each of nine human liver RNA samples contained a species of mRNA hybridizable to a cloned HLj cDNA. We conclude that HLj is related by structure, function, and some regulatory characteristics to rat P-450j and rabbit P-450 LM3a, cytochromes critical for metabolism of several clinically relevant cytotoxic and carcinogenic agents.