Activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin

Alcohols and aldehydes in the metabolic pathways of ethanol and serotonin a re substrates for alcohol dehydrogenases (ADH) of class I and II. In additi on to the reversible alcohol oxidation/aldehyde reduction, these enzymes ca talyse aldehyde oxidation. Class-I gamma gamma ADH catalyses the dismutatio n of both acetaldehyde and 5-hydroxyindole-3-acetaldehyde (5-HIAL) into the ir corresponding alcohols and carboxylic acids. The turnover of acetaldehyd e dismutation is high (k(cat) = 180 min(-1)) but saturation is reached firs t at high concentrations (K-m = 30 mM) while dismutation of 5-HIAL is satur ated at lower concentrations and is thereby more efficient (K-m = 150 mu M; k(cat) = 40 min(-1)). In a system where NAD(+) is regenerated the oxidatio n of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid proceeds with con centration levels of the intermediary 5-HIAL expected for a two-step oxidat ion. Butanal and 5-HIAL oxidation is also observed for class-I ADH in the p resence of NADH. The class-II enzyme is less efficient in aldehyde oxidatio n, and the ethanol-oxidation activity of this enzyme is competitively inhib ited by acetate (K-i = 12 mM) and 5-hydroxyindole-3-acetic acid (K-i = 2 mM ). Reduction of 5-HIAL is efficiently catalysed by class-I gamma gamma ADH (k( cat) = 300 min(-1); K-m = 33 mu M) in the presence of NADH. This indicates that the increased 5-hydroxytryptophol/5-hydroxyindole-3-acetic acid ratio observed after ethanol intake may be due to the increased NADH/NAD(+) ratio on the class-I ADH.