chi-ADH is the sole alcohol dehydrogenase isozyme of mammalian brains: implications and inferences.
Class III (chi) is the only alcohol dehydrogenase (ADH) in human, equine, bovine, simian, canine, and rodent brain and is the first to be identified, purified, and characterized from the brain of humans or other vertebrates. Like the corresponding isozymes from human placenta and liver, the chi-ADH isozymes purified from mammalian brain are neither inhibited by nor do they bind to immobilized pyrazole, and they oxidize ethanol only very poorly (Km greater than 2.5 M). Indeed, it would be incorrect to classify them as "ethanol dehydrogenases." They contain 4 g.atom of zinc/mol, bind 2 moles of NAD, and readily oxidize long-chain aliphatic and aromatic primary alcohols. These findings appear to exclude the possibilities that ADH protects the brain of these vertebrates against ethanol or its metabolic products and that the brain can generate energy for cerebral function from ADH-monitored ethanol metabolism. Thus chi-ADH must serve a totally different but as yet unknown role. The failure to detect any ethanol dehydrogenase activity in brain creates an intellectual dilemma only if it is assumed that such an enzyme has evolved and developed as a protective mechanism for ethanol detoxification in that organ, as has been assumed. Tissue and substrate specificities of ADH isozymes are likely to give new insight regarding their physiological roles.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001921:Brain / Q000201:enzymology*; D000431:Ethanol / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D013379:Substrate Specificity
D000596:Amino Acids; D007527:Isoenzymes; D000431:Ethanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase