title: Mechanism of action of Drosophila melanogaster alcohol dehydrogenase.
abstract: Reported kinetic pH dependence data for alcohol dehydrogenase from Drosophila melanogaster are analyzed with regard to differences in rate behaviour between this non-metallo enzyme and the zinc-containing liver alcohol dehydrogenase present in vertebrates. For the Drosophila enzyme a mechanism of action is proposed according to which catalytic proton release to solution during alcohol oxidation occurs at the binary-complex level as an obligatory step preceding substrate binding. Such proton release involves an ionizing group with a pKa of about 7.6 in the enzyme.NAD+ complex, tentatively identified as a tyrosyl residue. The ionized form of this group is proposed to participate in the binding of alcohol substrates and to act as a nucleophilic catalyst of the subsequent step of hydride ion transfer from the bound alcohol to NAD+. Herein lie fundamental mechanistic differences between the metallo and non-metallo short chain alcohol dehydrogenases.
authors.affiliation: Biochemical Institute, University of Oslo, Norway.
authors.forename: J S
authors.initials: JS
authors.lastname: McKinley-McKee
authors.forename: J O
authors.initials: JO
authors.lastname: Winberg
authors.forename: G
authors.initials: G
authors.lastname: Pettersson
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D014714:Vertebrates / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D000429:Alcohol Oxidoreductases; C073796:ADH protein, Drosophila; D000426:Alcohol Dehydrogenase; D015032:Zinc