Ethanol-inducible cytochrome P4502E1: regulation, enzymology and molecular biology.

Alcohol and alcoholism (Oxford, Oxfordshire). Supplement Pub Date : 1994-01-01

M Ingelman-Sundberg, M J Ronis, K O Lindros, E Eliasson, A Zhukov

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Abstract

Cytochrome P450 2E1 (CYP2E1) is constitutively expressed in liver and many other tissues. CYP2E1 is effectively induced in the liver by a diverse set of chemicals having various structures. The enzyme constitutes the only P450 form that is strongly induced by ethanol. CYP2E1 metabolizes a wide array of chemicals with different structures, in particular small and hydrophobic compounds, including potential carcinogens. In addition, CYP2E1 has a unique capacity to reduce dioxygen to reactive oxy radicals that might initiate membranous lipid peroxidation, yielding products, mainly aldehydes, which activate immune cells for cytokine production and Ito cells for collagen formation. CYP2E1 mediated formation of reactive lipid peroxidation products and alpha-hydroxyethyl radicals gives rise to protein adduct formation, some of which can cause autoimmune reactions. The regulation of CYP2E1 is unusually complicated and is exerted at several different cellular levels. CYP2E1 has received much attention, mainly because of its putative importance in the activation of chemicals to cytotoxic or carcinogenic products and its potential role in ethanol-induced hepatotoxicity.

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乙醇诱导细胞色素P4502E1:调控、酶学和分子生物学。

细胞色素P450 2E1 (CYP2E1)在肝脏和许多其他组织中组成性表达。CYP2E1在肝脏中被多种具有不同结构的化学物质有效诱导。这种酶是唯一一种能被乙醇强烈诱导的P450形式。CYP2E1代谢一系列具有不同结构的化学物质，特别是小分子和疏水性化合物，包括潜在的致癌物质。此外，CYP2E1具有将双氧还原为活性氧自由基的独特能力，这可能引发膜质脂质过氧化，产生产物，主要是醛，激活免疫细胞产生细胞因子和Ito细胞形成胶原。CYP2E1介导的反应性脂质过氧化产物和α -羟乙基自由基的形成引起蛋白质加合物的形成，其中一些可引起自身免疫反应。CYP2E1的调控异常复杂，并在几个不同的细胞水平上发挥作用。CYP2E1受到了广泛的关注，主要是因为它在化学物质活化成细胞毒性或致癌物中的重要性，以及它在乙醇诱导的肝毒性中的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Alcohol and alcoholism (Oxford, Oxfordshire). Supplement

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