Metabolism of alcohol at high concentrations: role and biochemical nature of the hepatic microsomal ethanol oxidizing system.

Abstract

At intermediate and higher alcohol concentrations, ethanol metabolism proceeds via alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS), whereas catalase plays no significant role. Following prolonged ethanol consumption, an enhancement of both MEOS activity as well as the rates of ethanol metabolism occurs; the latter persisted despite inhibition of ADH by pyrazole and catalase by sodium axide, suggesting the involvement of MEOS in the adaptive increase. MEOS exhibits characteristics similar to those of other microsomal drug metabolizing enzymes and can be differentiated and isolated from both ADH and catalase activities. Reconstitution of MEOS activity was achieved with partially purified cytochrome P-450 and NADPH-cytochrome c reductase in the presence of synthetic phospholipid.