title: The inhibition of xanthine oxidase by acetaldehyde in aqueous solution.
abstract: Xanthine oxidase (XO), catalyzes the sequential oxidation of hypoxanthine to xanthine and then to uric acid. The enzyme also catalyzes the oxidation of aldehydes to their corresponding carboxylic acids. In the present work we investigate the extent of inhibition of the xanthine oxidase-catalyzed oxidation of hypoxanthine by acetaldehyde/acetaldehyde hydrate system. At room temperature, aqueous solutions of acetaldehyde exist as equilibrated mixtures containing similar quantities of the aldehyde, CH3CHO and its hydrate CH3CH(OH)2. To determine whether acetaldehyde or its hydrate interacts with the enzyme to cause inhibition, the time course of enzymatic inhibition was observed in deoxygenated solutions of xanthine oxidase initially incubated with neat acetaldehyde and compared to that in which the enzyme was initially incubated with aqueous solutions containing both the aldehyde and its hydrate. Our results show that unhydrated acetaldehyde inhibits XO and that the inhibition of the XO-catalyzed oxidation of hypoxanthine progressively increases as the aldehyde is incubated with the enzyme. The data, taken together, suggest that enzymatic inhibition is the result of the reversible formation of covalently bound XO-acetaldehyde inhibitory compound. This investigation also demonstrates that the enzymatic oxidations of hypoxanthine and acetaldehyde take place on the same active site in XO.
authors.affiliation: Department of Chemistry, Seattle University, Washington 98122, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Aversa
authors.forename: J E
authors.initials: JE
authors.lastname: Meany
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D019271:Hypoxanthine / Q000378:metabolism; D007700:Kinetics; D012996:Solutions; D014867:Water; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D012996:Solutions; D014867:Water; D019271:Hypoxanthine; D014969:Xanthine Oxidase; D000079:Acetaldehyde