Common mechanism for the adaptive increase in hepatic ethanol and acetaldehyde metabolism due to chronic pretreatment with ethanol.
Perfused livers from ethanol pretreated rats utilized ethanol and acetaldehyde at higher rates than appropriate controls. This adaptive increase in hepatic ethanol and acetaldehyde uptake was associated with a marked (greater than 60%) increase in hepatic oxygen uptake. Ethanol uptake in both ethanol-treated and control livers was similarly sensitive to inhibition by 4-methylpyrazole, rotenone, and antimycin A. The adaptive increase in ethanol uptake was apparently specifically abolished by ouabain, an inhibitor of the sodium-plus potassium-activated ATPase. The data are consistent with the hypothesis that chronic treatment with ethanol increases ATPase activity. The ADP produced from these initiating events enters the mitochondrial space and stimulates electron transport and oxygen uptake. As a consequence of these events, a greater rate of NADH reoxidation occurs, resulting in a greater rate of production of NAD+ which stimulates ethanol oxidation via alcohol dehydrogenase and acetaldehyde oxidation via aldehyde dehydrogenase(s).
D000079:Acetaldehyde / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D011720:Pyrazoles; D000431:Ethanol; D010042:Ouabain; D000079:Acetaldehyde