A dual function of alcohol dehydrogenase in Drosophila

Abstract

Alcohol dehydrogenase (ADH) of Drosophila not only catalyzes the oxidation of ethanol to acetaldehyde, but additionally catalyzes the conversion of this highly toxic product into acetate. This mechanism is demonstrated by using three different methods. After electrophoresis the oxidation of acetaldehyde is shown in an NAD-dependent reaction revealing bands coinciding with the bands likewise produced by a conventional ADH staining procedure. In spectrophotometric measurements acetaldehyde is oxidized in an NADdependent reaction. This activity is effectively inhibited by pyrazole, a specific inhibitor of ADH. By means of gas chromatographic analysis a quick generation of acetate from ethanol could be demonstrated. Our conclusion is further supported by experimental results obtained with either purified ADH F enzyme or genotypes with or without ADH, aldehyde-oxidase, pyridoxal-oxidase and xanthine-dehydrogenase activity. These results are discussed in relation to ethanol tolerance in the living organism in particular with respect to differences found between ADH in Drosophila melanogaster and D. simulans, and in relation to the possible implications for the selective forces acting on ADH-polymorphism.

Kinetics and thermodynamics of ethanol oxidation catalyzed by genetic variants of the alcohol dehydrogenase from Drosophila melanogaster and D. simulans

“…The thermodynamic parameters as derived from the kinetic constants are given in Table III (Table III). [12,14,22,30,[33][34][35]. Preliminary studies indicated that during initial periods of ethanol oxidation, the ratio of product formation of acetaldehyde/acetate is about 8:1 [35].…”

“…does not breed in such habitats [18]. ADH plays the major role in the in vivo elimination of ethanol [12,22,23,30,33]. Therefore, ADH is thought to be a fundamental factor in the difference in habitats between the two species.…”

Ethanol and Isopropanol detoxification associated with the Adh locus of Drosophila melanogaster

“…In any case, ethanol is transformed into acetaldehyde which is further converted into acetate and thus used as metabolic energy through the Krebs cycle (Clarke, 1975;David et a!., 1976;David, 1977;DeltombeLietaert et a!., 1979). ADH isozymes seem to have a dual function catalysing both ethanol and acetaldehyde oxidations in D. melanogaster (Heinstra et al, 1983). Ethanol and other primary alcohols can be clearly used as food by D. melanogaster, increasing the life span of flies deprived of other food resources (van Herrewege and David, 1974;Deltombe-Lietaert et a!., 1979;Andeson et aL, 1981;Dorado and Barbancho, 1984), and even when the flies are exposed only to ethanol vapour (van Herrewege and David, 1978).…”

Participation of Drosophila melanogaster alcohol dehydrogenase (ADH) in the detoxification of 1-pentene-3-ol and 1-pentene-3-one

“…ADH enzymes catalyze the oxidation of primary and secondary alcohols into aldehydes and ketones, respectively. However, while aldehydes are further metabolized by means of an aldehyde dehydrogenase (David et al, 1984) and/or the ADH itself (Heinstra et at., 1983(Heinstra et at., , 1986bEisses et al, 1985;Moxom et a!., 1985), ketones seem to be metabolic dead ends (David et a!., 1981;Heinstra eta!., 1986a). In fact, primary alcohols can be used by Drosophila as food, while secondary ones cannot (van Herrewege et a!., 1980;Sánchez-Cañete et a!., 1986).…”