A Chemical Mechanistic Path Leads the Way to Cellular Argpyrimidine.

ABSTRACT: Argpyrimidine (APY) is a methylglyoxal-derived advanced glycation end-product (AGE) that has been associated with multiple diseases. As APY forms without an enzyme, it remains exceptionally difficult to pinpoint where APY is likely to be found, both on individual proteins and in cells. In this study, we used a peptide model system and mass spectrometry analysis to investigate the chemical mechanism through which APY arises from methylglyoxal (MGO), a biologically relevant glycating agent. Consistent with other proposed APY formation mechanisms, our results identify AGE species with a mass change of [M + 144], presumably including tetrahydropyrimidine (THP), as a direct precursor to APY. However, our results rule out previously proposed reductone or oxidative decarboxylation mechanisms. Ins

SUBMITTER: Tin Pham VT 

PROVIDER: S-EPMC12550834 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature