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The alcohol-inducible form of cytochrome P450 (CYP2E1): Role in toxicology and regulation of expression

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Abstract

Cytochrome P450 (CYP) 2E1 catalyzes the metabolism of a wide variety of therapeutic agents, procarcinogens, and low molecular weight solvents. CYP2E1-catalyzed metabolism may cause toxicity or DNA damage through the production of toxic metabolites, oxygen radicals, and lipid peroxidation. CYP2E1 also plays a role in the metabolism of endogenous compounds including fatty acids and ketone bodies. The regulation of CYP2E1 expression is complex, and involves transcriptional, post-transcriptional, translational, and post-translational mechanisms. CYP2E1 is transcriptionally activated in the first few hours after birth. Xenobiotic inducers elevate CYP2E1 protein levels through both increased translational efficiency and stabilization of the protein from degradation, which appears to occur primarily through ubiquitination and proteasomal degradation. CYP2E1 mRNA and protein levels are altered in response to pathophysiologic conditions by hormones including insulin, glucagon, growth hormone, and leptin, and growth factors including epidermal growth factor and hepatocyte growth factor, providing evidence that CYP2E1 expression is under tight homeostatic control.

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  1. Institute of Chemical Toxicology, Wayne State University, 2727 Second Avenue, Room 4000, 48201, Detroit, MI, USA

    Raymond F. Novak & Kimberley J. Woodcroft

  2. EHS Center in Molecular and Cellular Toxicology with Human Applications, Wayne State University, 48201, Detroit, Michigan, USA

    Raymond F. Novak & Kimberley J. Woodcroft

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Novak, R.F., Woodcroft, K.J. The alcohol-inducible form of cytochrome P450 (CYP2E1): Role in toxicology and regulation of expression. Arch Pharm Res 23, 267–282 (2000). https://doi.org/10.1007/BF02975435

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