title: Alcohol dehydrogenase polymorphism in Drosophila: enzyme kinetics of product inhibition.
abstract: Because natural populations of Drosophila melanogaster are polymorphic for different allozymes of alcohol dehydrogenase (ADH) and because D. melanogaster is more tolerant to the toxic effects of ethanol than its sibling species D. simulans, information regarding the sensitivities of the different forms of ADH to the products of ethanol degradation are of ecological importance. ADH-F, ADH-S, ADH-71k of D. melanogaster and the ADH of D. simulans were inhibited by NADH, but the inhibition was relieved by NAD+. The order of sensitivity to NADH was ADH-F less than ADH-71k, ADH-S less than ADH-simulans with ADH-F being about four times less sensitive than the D. melanogaster enzymes and 12 times less sensitive than the D. simulans enzyme. Acetaldehyde inhibited the ethanol-to-acetaldehyde activity of the ADHs, but at low acetaldehyde concentrations ethanol and NAD+ reduced the inhibition. ADH-71k and ADH-F were more subject to the inhibitory action of acetaldehyde than ADH-S and ADH-simulans, with ADH-71k being seven times more sensitive than ADH-S. The pattern of product inhibition of ADH-71k suggests a rapid equilibrium random mechanism for ethanol oxidation. Thus, although the ADH variants only differ by a few amino acids, these differences exert a far larger impact on their intrinsic properties than previously thought. How differences in product inhibition may be of significance in the evolution of the ADHs is discussed.
authors.affiliation: Department of Population and Evolutionary Biology, University of Utrecht, The Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: Heinstra
authors.forename: W
authors.initials: W
authors.lastname: Scharloo
authors.forename: G E
authors.initials: GE
authors.lastname: Thorig
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics*; D000818:Animals; D004330:Drosophila / Q000201:enzymology / Q000235:genetics*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D007700:Kinetics; D009243:NAD / Q000378:metabolism; D011110:Polymorphism, Genetic; D013045:Species Specificity
chemical_list: D009243:NAD; D000426:Alcohol Dehydrogenase