Abstract
Urate oxidase (uricase) from Candida utilis, an essential thiol enzyme, was examined for its sensitivity to myeloperoxidase, an oxidant present in neutrophils. Upon exposure to a system composed of myeloperoxidase, hydrogen peroxide and chloride at neutral or moderately alkaline pH, the uricase exhibited comparable activity to the untreated enzyme; but upon exposure at moderately acidic pH, it exhibited less than 8.0±3.0 (mean ± SE, n= 5) % of the activity of the untreated enzyme. Thus the myeloperoxidase-H2O2-chloride system significantly inactivated uricase only at moderately acidic pH. This inactivation was prevented by the presence of N-acetylmethionine, a methionine analogue and a thioether compound, or glutathione, a thiol compound analogous to amino acid, indicating that it was due to the oxidation and damage of the methionine residue and/or the thiol group in uricase by the myeloperoxidase system, accompanying the loss of catalytic activity of the uricase.
