Human alcohol dehydrogenases and serotonin metabolism.
Human liver alcohol dehydrogenases (ADH) may participate in serotonin (5-hydroxytryptamine) metabolism. Class I and II isozymes catalyze the oxidation of 5-hydroxytryptophol (5-HTOL) with kcat/Km values ranging from 10 to 100 mM-1 min-1 compared to 4-66 mM-1 min-1 for that of ethanol at pH 7.40, 25 degrees C. The product, 5-hydroxyindoleacetaldehyde, was purified as its semicarbazone and identified by mass spectrometry. Ethanol competitively inhibits 5-HTOL oxidation by beta 1 gamma 2 ADH with a Ki of 440 microM, a value similar to the Km of ethanol, 210 microM. The inhibition constants for 1,10-phenanthroline and 4-methylpyrazole are 20 microM and 80 nM respectively, essentially identical to those obtained with ethanol as substrate, 22 microM and 70 nM, respectively. The competition between ethanol and 5-HTOL for ADH can explain observations of ethanol induced changes in serotonin metabolism in vivo.
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism; D000077604:Fomepizole; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006917:Hydroxytryptophol / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008433:Mathematics; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
D007527:Isoenzymes; D010618:Phenanthrolines; D011720:Pyrazoles; D006917:Hydroxytryptophol; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; C025205:1,10-phenanthroline