Ethanol-inducible liver cytochrome P-450 in the rat: relative specificity for ethanol oxidation activity in vitro.
Ethanol induces in rat liver microsomes a form of cytochrome P-450 differing in substrate specificity from cytochrome P-450 species present in controls or in rats treated with phenobarbital or 3-methylcholanthrene. Its relative capacity to oxidize ethanol remained to be determined and was studied using highly purified cytochrome P-450 preparations and comparing their activity in a reconstituted microsomal ethanol oxidizing system (MEOS). On a molar basis, reconstituted MEOS activity was found to be highest when assayed with ethanol-inducible cytochrome P-450, intermediate with cytochrome P-450 from phenobarbital-treated rats, and lowest with cytochrome P-450 from controls or 3-methylcholanthrene-treated rats. A decrease in apparent Km for ethanol was also found to be associated with higher MEOS activity of ethanol-inducible cytochrome P-450. The induction by ethanol of a catalytically distinct form of cytochrome P-450, and the comparatively high ethanol oxidizing activity of this cytochrome P-450 species, are in accordance with the MEOS hypothesis.
D000079:Acetaldehyde / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008748:Methylcholanthrene / Q000494:pharmacology; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013379:Substrate Specificity
D000431:Ethanol; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D000079:Acetaldehyde; D010634:Phenobarbital