The mechanism of orotidine 5 '-monophosphate decarboxylase: Catalysis by destabilization of the substrate

The mechanism of orotidine 5'-monophosphate decarboxylase (OMP decarboxylas e, ODCase) was studied using the decarboxylation of orotic acid analogues a s a model system, The rate of decarboxylation of 1,3-dimethylorotic acid an d its analogues as well as the stability of their corresponding carbanion i ntermediates was determined. The results have shown that the stability of t he carbanion intermediate is not a critical factor in the rate of decarboxy lation. On the other hand, the reaction rate is largely dependent on the eq uilibrium constant for the formation of a zwitterion. Based on these result s, we have proposed a new mechanism in which ODCase catalyzes the decarboxy lation of OMP by binding the substrate in a zwitterionic form and providing a destabilizing environment for the carboxylate group of OMP.