Contribution of Aldehyde Oxidase, Xanthine Oxidase, and Aldehyde Dehydrogenase on the Oxidation of Aromatic Aldehydes

• Published in: Chemical research in toxicology Vol. 17; no. 10; pp. 1368 - 1376
• Main Authors: Panoutsopoulos, Georgios I, Kouretas, Demetrios, Beedham, Christine
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-10-2004
• Subjects: Aldehyde Dehydrogenase - metabolism; Aldehyde Oxidase - metabolism; Aldehydes - metabolism; Amines - metabolism; Animals; Benzaldehydes - pharmacology; Cattle; Dopamine - metabolism; Enzyme Inhibitors - pharmacology; Guinea Pigs; Hydrocarbons, Aromatic - metabolism; Liver - drug effects; Liver - enzymology; Norepinephrine - metabolism; Oxidation-Reduction; Phenylacetates - metabolism; Time Factors; Xanthine Oxidase - metabolism
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx030059u

Aliphatic aldehydes have a high affinity toward aldehyde dehydrogenase activity but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. In addition, the oxidation of xenobiotic-derived aromatic aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase, and xanthine oxidase activities in the oxidation of substituted benzaldehydes in separate preparations. The incubation of vanillin, isovanillin, and protocatechuic aldehyde with either guinea pig liver aldehyde oxidase, bovine milk xanthine oxidase, or guinea pig liver aldehyde dehydrogenase demonstrated that the three aldehyde oxidizing enzymes had a complementary substrate specificity. Incubations were also performed with specific inhibitors of each enzyme (isovanillin for aldehyde oxidase, allopurinol for xanthine oxidase, and disulfiram for aldehyde dehydrogenase) to determine the relative contribution of each enzyme in the oxidation of these aldehydes. Under these conditions, vanillin was rapidly oxidized by aldehyde oxidase, isovanillin was predominantly metabolized by aldehyde dehydrogenase activity, and protocatechuic aldehyde was slowly oxidized, possibly by all three enzymes. Thus, aldehyde oxidase activity may be a significant factor in the oxidation of aromatic aldehydes generated from amines and alkyl benzenes during drug metabolism. In addition, this enzyme may also have a role in the catabolism of biogenic amines such as dopamine and noradrenaline where 3-methoxyphenylacetic acids are major metabolites.