Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1.
Cytochrome P450IIE1 is involved in the metabolic activation of many xenobiotics involved with human toxicity. In particular, cellular concentrations of P450IIE1 are significantly induced by the most widely abused drug in our society today, alcohol. As a result, the synthesis and degradation of this form of P450 has significant health consequences. The regulation of the steady-state concentration of P450IIE1 is an extremely complex process. The enzyme is regulated by transcriptional activation, mRNA stabilization, increased mRNA translatability and decreased protein degradation. The principal mechanism which controls the induction process depends on the chemical nature of the inducer, the age, and the nutritional and hormonal status of the animal. There also appear to be significant sex differences in the expression of P450IIE1. It is entirely possible that the regulation of the enzyme concentration under any given set of conditions will involve all of the mechanisms to different extents.
Koop
D R
DR
Department of Environmental Health Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106.
Tierney
D J
DJ
D000818:Animals; D001711:Biotransformation; D006224:Cricetinae; D019392:Cytochrome P-450 CYP2E1; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D005810:Multigene Family; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000235:genetics*; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012737:Sex Factors; D014158:Transcription, Genetic
D012333:RNA, Messenger; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating