Open AccessActivities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin
Author(s) -
Svensson Stefan,
Some Margareta,
Lundsjö Anders,
Helander Anders,
Cronholm Tomas,
Höög JanOlov
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00351.x
Subject(s) - acetaldehyde , chemistry , aldehyde , aldehyde dehydrogenase , alcohol dehydrogenase , ethanol , acetic acid , alcohol , nad+ kinase , alcohol oxidation , enzyme , stereochemistry , organic chemistry , biochemistry , catalysis
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 γγ 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 ( k cat = 180 min −1 ) but saturation is reached first at high concentrations ( K m = 30 m m ) while dismutation of 5‐HIAL is saturated at lower concentrations and is thereby more efficient ( K m = 150 µ m ; k cat = 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 ( K i = 12 m m ) and 5‐hydroxyindole‐3‐acetic acid ( K i = 2 m m ). Reduction of 5‐HIAL is efficiently catalysed by class‐I γγ ADH ( k cat = 400 min −1 ; K m = 33 µ 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.