Ethanol oxidation in systems containing soluble and mitochondrial fractions of rat liver. Regulation by acetaldehyde.
Systems containing soluble fraction of rat liver, with or without mitochondrial fraction, oxidised [1-14C] ethanol to acetaldehyde, 14CO2 and non-volatile 14C-products of which acetate was the principal, and possibly the only, component. Ethanol oxidation was stimulated by pyruvate which served as an electron sink thereby allowing rapid regeneration of NAD. When no mitochondria were present acetaldehyde accumulated, rapidly at first but eventually reaching a plateau. The rate of ethanol oxidation in these systems was much lower than the measured maximum activity of alcohol dehydrogenase (ADH) and it was concluded that ADH was inhibited by the accumulated acetaldehyde. Mitochondria, because of their relatively high aldehyde dehydrogenase (ALDH) activity, prevented the accumulation of acetaldehyde, or quickly removed acetaldehyde already accumulated. This action was accompanied by a sharp increase in the rate of ethanol oxidation, presumably due to the deinhibition of ADH. Cyanamide, an inhibitor of mitochondrial ALDH, blocked the stimulatory effect of mitochondria on ethanol oxidation. It was concluded that, in the reconstituted systems, acetaldehyde played a dominant role in controlling the rate of ethanol oxidation. The possible importance of acetaldehyde in governing ethanol oxidation in vivo is discussed.
D000079:Acetaldehyde / Q000032:analysis*; D000085:Acetates / Q000032:analysis; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D003484:Cyanamide / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D011773:Pyruvates; D009243:NAD; D000431:Ethanol; D003484:Cyanamide; D000429:Alcohol Oxidoreductases; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde