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从用2,3,7,8-四氯二苯并对二恶英处理过的兔肝脏微粒体中分离出两种细胞色素P-450形式。

Resolution of two forms of cytochrome P-450 from liver microsomes of rabbit treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

作者信息

Johnson E F, Muller-Eberhard U

出版信息

J Biol Chem. 1977 May 10;252(9):2839-45.

PMID:404296
Abstract

Two forms of cytochrome P-450 with different substrate specificities were isolated from liver microsomes of rabbits treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A specific antibody was produced toward the major form of the cytochrome. The antibody inhibits microsomal acetanilide hydroxylation (80%). It does not cross-react with the minor fraction of the cytochrome or inhibit the hydroxylation of 3,4-benzpyrene or coumarin, the N-demethylation of aminopyrine or the O-deethylation of 7-ethoxycoumarin catalyzed by rabbit liver microsomes. The major form has an estimated Mr = 54,000 and displays an n-octylamine difference spectrum with an absorption maximum at 426 nm and a minimum at 391 nm. When reconstituted, this cytochrome catalyzes acetanilide hydroxylation at a higher rate than microsomes or the minor fraction. The n-octylamine difference spectrum of the minor fraction displays an absorption maximum at 431 nm and a minimum at 410 nm. When reconstituted, this fraction catalyzes the hydroxylation of 3,4-benzpyrene and the O-deethylation of 7-ethoxycoumarin. The two cytochromes appear to be distinct entities and function in different catalytic pathways.

摘要

从用2,3,7,8-四氯二苯并对二恶英(TCDD)处理过的兔肝脏微粒体中分离出两种具有不同底物特异性的细胞色素P-450形式。针对细胞色素的主要形式制备了一种特异性抗体。该抗体抑制微粒体乙酰苯胺羟基化(80%)。它与细胞色素的次要部分不发生交叉反应,也不抑制3,4-苯并芘或香豆素的羟基化、兔肝脏微粒体催化的氨基比林N-去甲基化或7-乙氧基香豆素的O-去乙基化。主要形式的估计分子量为54,000,呈现n-辛胺差异光谱,在426nm处有最大吸收峰,在391nm处有最小吸收峰。重组后,这种细胞色素催化乙酰苯胺羟基化的速率高于微粒体或次要部分。次要部分的n-辛胺差异光谱在431nm处有最大吸收峰,在410nm处有最小吸收峰。重组后,该部分催化3,4-苯并芘的羟基化和7-乙氧基香豆素的O-去乙基化。这两种细胞色素似乎是不同的实体,在不同的催化途径中发挥作用。

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引用本文的文献

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Administration of 3-methylcholanthrene to rats increases the specific hybridizable mRNA coding for cytochrome P-450c.给大鼠注射3-甲基胆蒽会增加编码细胞色素P-450c的特异性可杂交mRNA。
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4083-7. doi: 10.1073/pnas.78.7.4083.
2
Role of cytochrome P-450 and related enzymes in the pulmonary metabolism of xenobiotics.细胞色素P-450及相关酶在外源化学物肺代谢中的作用。
Environ Health Perspect. 1984 Apr;55:359-67. doi: 10.1289/ehp.8455359.
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Resolution and reconstitution of the forms of hepatic cytochrome P-450 from rabbits [proceedings].
兔肝细胞色素P-450形式的解析与重构[会议论文集]
Br J Pharmacol. 1979 Jul;66(3):427P.