The chemistry of xanthine oxidase. 10. The inhibition of the bovine enzyme by purine 6-aldehyde

Abstract

The powerful inhibitory action in vitro of purine 6-aldehyde on the aerobic oxidation of xanthine by bovine milk xanthine oxidase has been studied under various conditions. The onset of inhibition is slow, the rate being dependent on the concentration of the reactants, the presence or absence of the substrate and also the pH. Inhibition is maximal at pH 7.0 under the conditions used. The order of the reaction with respect to the purine aldehyde is fractional. The observations are consistent with the inhibitor being reversibly and strongly bound at the same site as the substrate and with a group at the active site having pK in the region 5.5-6.0. The unusual kinetics are tentatively ascribed to multipoint attachment of the inhibitor to the enzyme or to a change in the overall mechanism of xanthine oxidation.