Roles of Class III ADH (ADH3), a new alcohol metabolizing enzyme, on biosensitivities for alcohol

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We have recently demonstrated that alcohol dehydrogenase 3 (ADH3) participates in systemic alcohol metabolism. In this study, we used ADH knockout mice (Adh1-/-, Adh3-/-) to investigate the role of ADH3 in sex-difference of alcohol metabolism, in the production of acetaldehyde in major organs, in alcohol sensitivity and in alcohol preference, comparing with ADH1, a key enzyme of alcohol metabolism. ADH3 showed a sex-different contribution to systemic alcohol metabolism, contributing dose-dependently in male, but at middle doses (2-3g/kg) in female. On the other hand, the sex-differences of pharmacokinetics of blood alcohol found in both Wild and Adh3-/- could be explained by the sex-differences of ADH1 activity in the liver and of alcohol distribution rate (γ). ADH1 contributes to acetaldehyde production in the liver and kidney, whereas ADH3 only in the liver. In addition, ADH3 was found to play as a protective factor for acute alcohol poisoning, and as an alcohol-preferential factor, together with ADH1.