On the oxidation of aldehydes by alcohol dehydrogenase of Drosophila melanogaster: Evidence for the gem-diol as the reacting substrate

Medium- and short-chain dehydrogenase/reductase gene and protein families

“…This results in transfer of the pro-S hydrogen in ethanol to the coenzyme. However, in the further oxidation of aldehydes to acids, the alkyl chain of the aldehyde binds to the R 2 part of the active site [32], a finding that supported the suggestion [43] that the gem-diol form of aldehydes binds to the binary enzyme-NAD + complex in the oxidation of an aldehyde to the corresponding carboxylic acid. The crystal structure data also indicate that one of the hydroxyl groups in the gem-diol are at hydrogen bonding distance to the hydroxyl group in the side chain of the active site Ser138 and Tyr51, while the other hydroxyl group points into the R 1 b cavity close to the C7-amide group of the nicotinamide moiety of the coenzyme.…”

Drosophila Alcohol Dehydrogenase: Acetate–Enzyme Interactions and Novel Insights into the Effects of Electrostatics on Catalysis

“…In any case, the formed acetaldehyde in its carbonyl form must be hydrated to its gem-diol form to be oxidized. 33 If the gem-diol is formed in the active site prior to its rearrangement in the active site, it would be expected that the presence of semicarbazide should not trap the aldehyde and prevent it from oxidation. To determine whether this was the case or not, we first studied the oxidation of ethanol to acetaldehyde by 1 H NMR.…”

“…Kinetic studies were consistent with an ordered reaction mechanism for both the interconversion of ethanol and acetaldehyde as well as for the oxidation of acetaldehyde to acetate. 28,29,[31][32][33] In these reactions, the oxidized and reduced coenzymes, NAD C and NADH, respectively, bind to the free enzyme E, and the ethanol and acetaldehyde bind to the binary enzyme-coenzyme complexes. It has also been suggested that the gem-diol form of acetaldehyde binds to the binary enzyme-NAD C complex in the oxidation of acetaldehyde to acetate, 33 and that this oxidation step is an irreversible reaction.…”

“…28,29,[31][32][33] In these reactions, the oxidized and reduced coenzymes, NAD C and NADH, respectively, bind to the free enzyme E, and the ethanol and acetaldehyde bind to the binary enzyme-coenzyme complexes. It has also been suggested that the gem-diol form of acetaldehyde binds to the binary enzyme-NAD C complex in the oxidation of acetaldehyde to acetate, 33 and that this oxidation step is an irreversible reaction. 28,29 However, nothing is known about the stereochemistry of the aldehyde oxidation reaction, i.e.…”

Evolutionary genetics of the Drosophila alcohol dehydrogenase gene-enzyme system

“…The probable in situ distribution of alcohol elimination in larvae is about 60% in the fat body and 30% in the alimentary tract (Heinstra et al, 1989;Fibia, Enjuanes & Gonzfilez, 1989;Anderson, Brown & McDonald, 1991). It appears that the ADH enzyme is involved in the in vivo conversion of acetaldehyde into acetate in larvae, whereas the aldehyde dehydrogenase (ALDH, EC 1.2.1.3) enzyme is mainly responsible for this conversion in adults (Heinstra et al, 1983(Heinstra et al, , 1989Eisses et al, 1985;Geer, Langevin & McKechnie, 1985;Geer, Miller & Heinstra, 1991;Moxon et al, 1985;Garcin et al, 1983Garcin et al, , 1985Eisses, 1989;Anderson & Barnett, 1991;Leal & Barbancho, 1992Miller, Heinstra & Geer, 1992). The biotransformation of the highly toxic compound acetaldehyde has been extensively studied and debated (e.g., David et al, 1978;Deltombe-Lietaert et al, 1979;Gelfand & McDonald, 1980;David, 1988).…”