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



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



Biochemistry 39(7): 1778-1783



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

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Accession: 011524743

Download citation: RISBibTeXText

PMID: 10677227

DOI: 10.1021/bi992553w


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