Role of alcohol P-450-oxygenase (APO) in microsomal ethanol oxidation

Abstract

The form of liver microsomal cytochrome P-450 induced by chronic administration of ethanol to rabbits, designated as P-450 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-450 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-450 in the oxidation of alcohols. That P-450 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-450 antibodies. We conclude that P-450 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.