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

Eur J Biochem. 1999 Jun;262(2):324-9. doi: 10.1046/j.1432-1327.1999.00351.x.


Alcohols and aldehydes in the metabolic pathways of ethanol and serotonin are substrates for alcohol dehydrogenases (ADH) of class I and II. In addition to the reversible alcohol oxidation/aldehyde reduction, these enzymes catalyse aldehyde oxidation. Class-I gammagamma ADH catalyses the dismutation of both acetaldehyde and 5-hydroxyindole-3-acetaldehyde (5-HIAL) into their corresponding alcohols and carboxylic acids. The turnover of acetaldehyde dismutation is high (kcat = 180 min-1) but saturation is reached first at high concentrations (Km = 30 mm) while dismutation of 5-HIAL is saturated at lower concentrations and is thereby more efficient (Km = 150 microm; kcat = 40 min-1). In a system where NAD+ is regenerated, the oxidation of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid proceeds with concentration levels of the intermediary 5-HIAL expected for a two-step oxidation. Butanal and 5-HIAL oxidation is also observed for class-I ADH in the presence of NADH. The class-II enzyme is less efficient in aldehyde oxidation, and the ethanol-oxidation activity of this enzyme is competitively inhibited by acetate (Ki = 12 mm) and 5-hydroxyindole-3-acetic acid (Ki = 2 mm). Reduction of 5-HIAL is efficiently catalysed by class-I gammagamma ADH (kcat = 400 min-1; Km = 33 microm) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / antagonists & inhibitors
  • Alcohol Dehydrogenase / metabolism*
  • Aldehydes / metabolism
  • Ethanol / metabolism*
  • Humans
  • Hydrogen / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Hydroxytryptophol / metabolism
  • Kinetics
  • NAD / metabolism
  • Oxidation-Reduction
  • Serotonin / metabolism*


  • Aldehydes
  • NAD
  • Hydroxytryptophol
  • Serotonin
  • Ethanol
  • Hydroxyindoleacetic Acid
  • Hydrogen
  • Alcohol Dehydrogenase