Urate as a physiological substrate for myeloperoxidase: Implications for hyperuricemia and inflammation

Abstract

Urate and myeloperoxidase (MPO) are associated with adverse outcomes in cardiovascular disease. In this study, we assessed whether urate is a likely physiological substrate for MPO and if the products of their interaction have the potential to exacerbate inflammation. Urate was readily oxidized by MPO and hydrogen peroxide to 5-hydroxyisourate, which decayed to predominantly allantoin. The redox intermediates of MP Owere reduced by urate with rate constants of 4.6 × 105 M-1 s-1 for compound I and 1.7×104 M-1 s-1 for compound II. Urate competed with chloride for oxidation by MPO and at hyperuricemic levels is expected to be a substantive substrate for the enzyme. Oxidation of urate promoted s..