title: Human class II (pi) alcohol dehydrogenase has a redox-specific function in norepinephrine metabolism.
abstract: Studies of the function of human alcohol dehydrogenase (ADH) have revealed substrates that are virtually unique for class II ADH (pi ADH). It catalyzes the formation of the intermediary glycols of norepinephrine metabolism, 3,4-dihydroxyphenylglycol and 4-hydroxy-3-methoxyphenylglycol, from the corresponding aldehydes 3,4-dihydroxymandelaldehyde and 4-hydroxy-3-methoxymandelaldehyde with Km values of 55 and 120 microM and kcat/Km ratios of 14,000 and 17,000 mM-1 X min-1; these are from 60- to 210-fold higher than those obtained with class I ADH isozymes. The catalytic preference of class II ADH also extends to benzaldehydes. The kcat/Km values for the reduction of benzaldehyde, 3,4-dihydroxybenzaldehyde and 4-hydroxy-3-methoxybenzaldehyde by pi ADH are from 9- to 29-fold higher than those for a class I isozyme, beta 1 gamma 2 ADH. Furthermore, the norepinephrine aldehydes are potent inhibitors of alcohol (ethanol) oxidation by pi ADH. The high catalytic activity of pi ADH-catalyzed reduction of the aldehydes in combination with a possible regulatory function of the aldehydes in the oxidative direction leads to essentially "unidirectional" catalysis by pi ADH. These features and the presence of pi ADH in human liver imply a physiological role for pi ADH in the degradation of circulating epinephrine and norepinephrine.
authors.forename: G
authors.initials: G
authors.lastname: Mårdh
authors.forename: A L
authors.initials: AL
authors.lastname: Dingley
authors.forename: D S
authors.initials: DS
authors.lastname: Auld
authors.forename: B L
authors.initials: BL
authors.lastname: Vallee
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D001547:Benzaldehydes / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010084:Oxidation-Reduction; D013379:Substrate Specificity
chemical_list: D000447:Aldehydes; D001547:Benzaldehydes; D008734:Methoxyhydroxyphenylglycol; D000426:Alcohol Dehydrogenase; C032175:benzaldehyde; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine