OMP decarboxylase: Phosphodianion binding energy is used to stabilize a vinyl carbanion intermediate

Orotidine 5′-monophosphate decarboxylase (OMPDC) catalyzes the exchange for deuterium from solvent D₂O of the C-6 proton of 1-(β-d-erythrofuranosyl)-5-fluorouracil (FEU), a phosphodianion truncated product analog. The deuterium exchange reaction of FEU is accelerated 1.8 × 10⁴-fold by 1 M phosphite dianion (HPO₃ ^2-). This corresponds to a 5.8 kcal/mol stabilization of the vinyl carbanion-like transition state, which is similar to the 7.8 kcal/mol stabilization of the transition state for OMPDC-catalyzed decarboxylation of a truncated substrate analog by bound HPO₃^2-. These results show that the intrinsic binding energy of phosphite dianion is used in the stabilization of the vinyl carbanion-like transition state common to the decarboxylation and deuterium exchange reactions.