Abstract: Orotidine 5'-phosphate decarboxylase (ODase) catalyzes the conversion of orotidylate to uridylate, the last step in the de novo biosynthesis of pyrimidine nucleotides. Model reactions are described that support a covalent catalytic mechanism for this enzyme in which, following protonation of the carboxyl group of orotidylic acid, an active-site nucleophile undergoes a Michael addition to the C-5 position. This covalent complex ...