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微粒体乙醇氧化系统:细胞色素P450,CYP2E1的转录和转录后调控

Microsomal ethanol oxidizing system: transcriptional and posttranscriptional regulation of cytochrome P450, CYP2E1.

作者信息

Gonzalez F J, Ueno T, Umeno M, Song B J, Veech R L, Gelboin H V

机构信息

Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

出版信息

Alcohol Alcohol Suppl. 1991;1:97-101.

PMID:1845601
Abstract

CYP2E1 is solely responsible for microsomal P450-mediated ethanol oxidation activity. This enzyme is also involved in a pathway leading to gluconeogenesis from ketone bodies and in metabolic activation of numerous foreign compounds to intermediates that can be toxic to cells. Metabolic activation of certain procarcinogens by CYP2E1 may also lead to cell transformation. Regulation of CYP2E1 is especially intriguing. The CYP2E1 gene is transcriptionally activated in rat liver from a dormant state within a few hours after birth. This activation is due in part to the participation of a transcription factor designated hepatocyte nuclear factor 1 or HNF-1. In adult animals, constitutive expression of the enzyme is controlled to some degree by growth hormone. CYP2E1 is also regulated by many of its substrates through a substrate-induced stabilization of the enzyme. Under extreme conditions of fasting and uncontrolled diabetes CYP2E1 mRNA is stabilized.

摘要

细胞色素P450 2E1(CYP2E1)单独负责微粒体P450介导的乙醇氧化活性。该酶还参与了一条从酮体生成糖异生的途径,以及许多外来化合物代谢活化为对细胞有毒的中间体的过程。CYP2E1对某些前致癌物的代谢活化也可能导致细胞转化。CYP2E1的调控尤其引人关注。CYP2E1基因在大鼠肝脏中出生后数小时内从休眠状态被转录激活。这种激活部分归因于一种名为肝细胞核因子1(HNF-1)的转录因子的参与。在成年动物中,该酶的组成型表达在一定程度上受生长激素控制。CYP2E1也受到其许多底物的调控,通过底物诱导的酶稳定性。在禁食和未控制的糖尿病等极端条件下,CYP2E1 mRNA会稳定下来。

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