Xenobiotic-inducible Transcription of Cytochrome P450 Genes

Numerous foreign chemicals (xenobiotics) confront us daily; such compounds often are lipophilic and may accumulate to toxic levels unless they are metabolized to water-soluble products that can be readily excreted. A cytochrome P450 enzyme(s) often catalyzes the initial step in such detoxification p...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-08, Vol.270 (31), p.18175-18178
Main Authors: Denison, Michael S., Whitlock, James P.
Format: Article
Language:English
Subjects:
Cytochrome P-450 Enzyme System - genetics
Enzyme Induction
Hydrocarbons - pharmacology
Microbodies - drug effects
Phenobarbital - pharmacology
Steroids - pharmacology
Transcription, Genetic
Xenobiotics - pharmacology
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Summary:Numerous foreign chemicals (xenobiotics) confront us daily; such compounds often are lipophilic and may accumulate to toxic levels unless they are metabolized to water-soluble products that can be readily excreted. A cytochrome P450 enzyme(s) often catalyzes the initial step in such detoxification pathways. Multiple forms of cytochrome P450 exist; these enzymes are notable for their broad and overlapping substrate specificities. Although P450s usually mediate detoxification reactions, under some circumstances they activate their substrates to carcinogenic, mutagenic, and/or cytotoxic products. They also contribute to the oxidative metabolism of endogenous hormones, fatty acids, and cytokines. Some cytochrome P450 genes are expressed constitutively, while others (particularly those involved in xenobiotic metabolism) are inducible. In many cases, inducers are also substrates for the induced enzymes; therefore, P450 activities remain elevated only as needed. Enzyme induction usually enhances detoxification; thus, under most conditions, induction is a protective mechanism. Induction most often occurs at the level of transcription. The inducible cytochrome P450 enzymes represent interesting experimental systems for analyzing the mechanisms by which small molecules enhance the transcription of specific genes. Such knowledge can provide insights into gene regulation that are of relatively broad interest. Here, we briefly summarize the mechanisms by which xenobiotics induce cytochrome P450 gene transcription.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.31.18175