Ethanol metabolism in Peromyscus genetically deficient in alcohol dehydrogenase

Abstract

Ethanol metabolism was compared in two strains of the deermouse, Peromyscus maniculatus. Animals of the Adh N/ Adh N strain, which lack liver alcohol dehydrogenase (ADH) activity, eliminated ethanol at a signficantly slower rate (P < 0.0005) than those of the Adh F/ Adh Fstrain, which have normal liver ADH activity. However, a comparison of the blood ethanol elimination rate (BEER) in the two strains indicated that, at high blood ethanol concentrations, non-ADH mediated pathways may account for as much as two-thirds of normal ethanol elimination in this species. Chronic ethanol consumption induced an elevated BEER in Adh F/ Adh F mice but not in AdhN/ Adh N mice. This strain difference in response to ethanol feeding suggests that increases in BEER are mediated primarily via the ADH pathway. A microsomal ethanol-oxidizing system (MEOS), independent of ADH and catalase, was shown to exist in microsomal preparations from both strains of P. maniculatus. MEOS activity of naive Adh N/ Adh N mice was 2.3-fold higher than that of naive Adh F/ Adh H animals. Both strains had a 3-fold greater MEOS activity following chronic ethanol consumption. Contrary to similar investigations in ethanol-fed rats, the alteration in MEOS activity was not accompanied by significant changes in cytochrome P-450, NADPH-cytochrome c reductase or phospholipid. Most importantly, the elevated in vitro MEOS activity of ethanol-fed Adh N/ Adh N mice had no significant effect upon BEER. These results suggest caution in attaching physiological significance to the simultaneous, ethanol-induced increase of the in vitro MEOS and of BEER in experimental animals with normal liver ADH activities.