Role of alcohol P-450-oxygenase (APO) in microsomal ethanol oxidation.
The form of liver microsomal cytochrome P-450 induced by chronic administration of ethanol to rabbits, designated as P-450ALC or P-450 isozyme 3a, has been purified to homogeneity as judged by several criteria, including NH2- and COOH-terminal amino acid sequence determination. The reconstituted alcohol-P-450 oxygenase (APO) system containing P-450ALC and NADPH-cytochrome P-450 reductase catalyzes the oxidation of a variety of primary and secondary alcohols to aldehydes and ketones, including methanol, ethanol, n-propanol, n-butanol, 2-butanol, n-pentanol, and cyclohexanol. Other purified P-450 cytochromes, including isozymes 2, 3b, 3c, 4, and 6, are much less active than P-450ALC in the oxidation of alcohols. That P-450ALC functions in ethanol oxidation in liver microsomal membranes as well as in the reconstituted system was shown by immunochemical experiments involving inhibition by sheep anti-P-450ALC antibodies. We conclude that P-450ALC is the predominant ethanol-oxidizing cytochrome present after induction by chronic alcohol administration and that the other P-450 cytochromes have low but significant activity in both control and ethanol-induced animals.
D000438:Alcohols / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000502:physiology*; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism*; D007527:Isoenzymes / Q000032:analysis; D008099:Liver / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits
D000438:Alcohols; D007527:Isoenzymes; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System