The mechanism of orotidine 5'-monophosphate decarboxylase: catalysis by destabilization of the substrate.
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.
Feng
W Y
WY
Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, California 94132, USA.
Austin
T J
TJ
Chew
F
F
Gronert
S
S
Wu
W
W
D002384:Catalysis; D003653:Decarboxylation; D004795:Enzyme Stability; D007700:Kinetics; D013058:Mass Spectrometry; D008956:Models, Chemical; D009962:Orotate Phosphoribosyltransferase / Q000737:chemistry*; D009963:Orotic Acid / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D011522:Protons; D013379:Substrate Specificity
D011522:Protons; D009963:Orotic Acid; D009962:Orotate Phosphoribosyltransferase; D010100:Oxygen