Activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin.
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.
Svensson
S
S
Department of Medical Biochemistry, Karolinska Institutet, Stockholm, Sweden.
Some
M
M
Lundsjö
A
A
Helander
A
A
Cronholm
T
T
Höög
J O
JO
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006917:Hydroxytryptophol / Q000378:metabolism; D007700:Kinetics; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D012701:Serotonin / Q000378:metabolism*
D000447:Aldehydes; D009243:NAD; D006917:Hydroxytryptophol; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D006859:Hydrogen; D000426:Alcohol Dehydrogenase