ALCOHOL-DEHYDROGENASE (ADH) ISOZYMES IN THE ADH(N) ADH(N) STRAIN OF PEROMYSCUS-MANICULATUS (ADH(-) DEERMOUSE) AND A POSSIBLE ROLE OF CLASS-III ADH IN ALCOHOL METABOLISM/

Although the Adh(N)/Adh(N) strain of Peromyscus maniculatus (so-called ADH(-) deermouse) has been previously considered to be deficient in A DH, we found ADH isozymes of Classes II and III but not Class I in the liver of this strain. On the other hand the Adh(F)/Adh(F) strain (so- called ADH(+) deermouse), which has liver ADH activity, had Class I an d III but not Class II ADH in the liver. In the stomach, Class III and IV ADHs were detected in both deermouse strains, as well as in the dd Y mouse, which has the normal mammalian ADH system with four classes o f ADH. These ADH isozymes were identified as electrophoretic phenotype s on the basis of their substrate specificity, pyrazole sensitivity, a nd immunoreactivity. Liver ADH activity of the ADH(-) strain was barel y detectable in a conventional ADH assay using 15 mM ethanol as substr ate; however; it increased markedly with high concentrations of ethano l (up to 3 M) or hexenol (7 mM). Furthermore, in a hydrophobic reactio n medium containing 1.0 M t-butanol, liver ADH activity of this strain at low concentrations of ethanol (<100 mM) greatly increased (about s evenfold), to more than 50% that of ADH(+) deermouse. These results we re attributable to the presence of Class III ADH and the absence of Cl ass I ADH in the liver of ADH(-) deermouse. It was also found that eve n the ADH(+) strain has low liver ADH activity (< 40% that of the ddY mouse) with 25 mM ethanol as substrate, probably due to law activity i n Class I ADH. Consequently, liver ADH activity of this strain was low er than its stomach ADH activity, in contrast with the ddY mouse, whos e ADH activity was much higher in the liver than in the stomach, as we ll as other mammals. Thus, the ADH systems in both ADH(-) and ADH(+) d eermouse were different not only from each other but also from that in the ddY mouse; the ADH(-) strain was deficient in only Class I ADH, a nd the ADH(+) strain was deficient in Class II ADH and down-regulated in Class I ADH activity. Therefore, Class III ADH, which was found in both strains and activated allosterically, may participate in alcohol metabolism in deermouse, especially ill the ADH(-) strain.