Uridine 5'-monophosphate synthesis by orotidine 5'-phosphate decarboxylase was modeled taking into account a detailed reaction pathway and formation of all possible intermediates. Contributions from zwitterion mechanism, covalent mechanism, carbene mechanism and kinetic mechanism were taken into account to develop a branched mechanism. The model equations comprising of simultaneous partial differential equations describing the temporal variation of substrate concentrations were simultaneously solved and regression was carried out to determine the optimal rate parameters. The model was successful in describing the kinetics of the reaction with enzyme derived from yeast and predicting the complete substrate consumption for enzyme derived from human domain. The model also correctly described and predicted the substrate inhibition characteristics for both the observations. The model is, therefore, expected to provide reliable kinetic description of the reaction irrespective of the enzyme source. (C) 2015 Elsevier Ltd. All rights reserved.