Cytochrome P-450C-M/F, a new constitutive form of microsomal cytochrome P-450 in male and female rat liver with estrogen 2- and 16 alpha-hydroxylase activity.
Cytochrome P-450C-M/F, a new constitutive form of microsomal cytochrome P-450 in male and female rat liver with estrogen 2- and 16 alpha-hydroxylase activity.
复制标题
细胞色素 P-450C-M/F，雄性和雌性大鼠肝脏中微粒体细胞色素 P-450 的新组成形式，具有雌激素 2- 和 16 α-羟化酶活性。
DOI：
10.1021/bi00402a028
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发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
Kappas,A
中科院分区：
文献类型：
--
作者：
Sugita,O;Sassa,S;Miyairi,S;Fishman,J;Kubota,I;Noguchi,T;Kappas,A
1987年9月24日摘要：一种新的细胞色素P-450同工酶，P-450 c。m/f>已从未处理的大鼠肝微粒体中纯化。纯化后的制剂是凝胶均质的，含有12-15 nmol的P450/mg蛋白质，最小分子量为48 500。P-450 c的NH 2-末端氨基酸序列。m/f值与其它P-450不同。微粒体免疫印迹分析表明，P-450 c.未给药雄性和雌性大鼠的肝脏中存在M/F。用苯巴比妥、3-甲基胆蒽或β-萘酮处理大鼠未诱导P-450 C。男/女。细胞色素P-450 C。M//F对7-乙氧基香豆素和7-乙氧基试卤灵的芳烃、睾酮、雄烯二酮和孕酮的O-脱乙基或羟基化反应活性很低。相反，它在乙基吗啡和苄非他明的N-去甲基化以及雌激素，特别是雌二醇的2-和16 α-羟基化中具有高度活性。这些研究表明，细胞色素P-450 C。M/F在雄性和雌性大鼠中均组成性存在，表明其可能参与雌二醇的氧化代谢，特别是参与雌二醇的子宫代谢产物雌三醇的形成。（细胞色素P-450是一组在混合功能氧化酶系统中充当末端氧化酶的微染色体血红素蛋白的集合术语（库珀等人，1965年）。这种多组分体系在多种外来化学品如药物的氧化中起着至关重要的作用（Conney，1967; Lu等人，1970）、致癌物（Thorgeirsson等人，1973年）和碳氢化合物（Orrenius & Ernster，1974年）以及各种
Revised Manuscript Received September 24, 1987 abstract: A new cytochrome P-450 isozyme, P-450c. m/f> has been purified from untreated rat liver microsomes. The purified preparation was electrophoretically homogeneous and contained 12-15 nmol of P450/mg of protein and had a minimum molecular weight of 48 500. The NH2-terminal amino acid sequence of P-450c. m/f was different from that of otherP-450’s. Immunoblot analysis of microsomes demonstrated that P-450c. M/F was present in the liver of untreated male as well as female rats. Treatment of rats with phenobarbital, 3-methylcholanthrene, or/3-naphthoflavone did not induce P-450C. M/F. Cytochrome P-450C. M//F exhibited little activities of 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylation or hydroxylation of arylhydrocarbon, testosterone, androstenedione, and progesterone. In contrast, it was highly active in N-demethylation of ethylmorphine and benzphetamine and in 2-and 16a-hydroxylation of estrogens, particularly that of estradiol. These studies establish that cytochrome P-450C. M/F is constitutively present in both male and female rats and suggest that it may be involved in the oxidative metabolism of estradiol, particularly in the formation of estriol, the uterotropic metabolite of estradiol.(Cytochrome P-450 is a collective term for a group of mi-crosomal hemeproteins that serve as the terminal oxidases in the mixed-function oxidase system (Cooper et al., 1965). This multicomponent system plays a vital role in the oxidation of a variety of foreign chemicals such as drugs (Conney, 1967; Lu et al., 1970), carcinogens (Thorgeirsson et al., 1973), and hydrocarbons (Orrenius & Ernster, 1974) as well as diverse