Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism.
Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria.
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000378:metabolism*; D000438:Alcohols; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D000438:Alcohols; D011720:Pyrazoles; D009243:NAD; D000431:Ethanol; D009249:NADP; D000429:Alcohol Oxidoreductases; D002374:Catalase; D000079:Acetaldehyde; D000640:Amitrole