Triuret: a novel product of peroxynitrite-mediated oxidation of urate

Abstract

Urate is an efficient antioxidant and has recently emerged as a competitive inhibitor of tyrosine nitration by peroxynitrite. In vivo and in vitro studies demonstrate the large extent to which urate prevents nitration and establish the biological importance of the reaction between urate and peroxynitrite. The existing lack of characterization of this reaction has led us to focus our studies upon the mechanism of urate oxidation and the products formed. An oxidation product has been previously isolated and mass spectrometry revealed a mass of 146, which spontaneously fragmented into several other ion peaks without use of MS/MS mode. Here, we propose the novel oxidation product to be triuret (H(2)NCONHCONHCONH(2)). Triuret accurately reproduced the peculiar mass spectrum. Identification of the oxidation product helps to develop the mechanism of peroxynitrite-mediated oxidation of urate and can help explain urate's potential as both an antioxidant for tyrosine nitration while paradoxically acting as a pro-oxidant for lipids and sulfhydryls.