Orotidine 5’-phosphate decarboxylase ODCase

Orotidine 5 -phosphate decarboxylase (ODCase, E. C. 4.1.1.23) catalyzes the decarboxylation of orotidine 5 -phosphate (OMP) to form uridine 5 -phos-phate in the sixth and final step of pyrimidine biosynthesis (Fig. 1) [1]. The discovery of ODCase in 1954 followed the identification, three years earlier, of orotic acid as the metabolic precursor of nucleic acids [2, 3]. ODCase is a distinct, monofunctional polypeptide in bacteria and fungi, whereas in mammals it combines with orotate phosphoribosyltransferase (OPRTase) to form the bifunctional enzyme UMP synthase. Human deficiencies in either OPRTase or ODCase activity result in an autosomal recessive disorder called hereditary orotic aciduria [4]. The disease is characterized by depleted levels of pyrimidine nucleotides in the blood and by the appearance of crystalline... 

Decarboxylation reactions are common in Nature and they are involved in many pathways, including decarboxylation of keto acids, amino acid conversions, and carbohydrate synthesis. Many decarboxylases use cofactors such as metal ions, pyridoxal 5 -phosphate, biotin, and flavin, but a small subset, for example, orotidine 5 -phosphate decarboxylase (ODCase) and methyhnalonyl CoA decarboxylase do not utilize any cofactor. ODCase catalyzes the decarboxylation of orotic acid (shown in Figure 8), and it generates one of the largest rate enhancements known to be produced by any enzyme (rate of the reaction is enhanced by a factor of Several... 

Enzymes catalyze many reactions far better than man-made catalysts. The goal of theoretical studies of enzyme mechanisms is to understand how they achieve their amazing catalytic power. In this respect, orotidine 5 -mono-phosphate decarboxylase (ODCase) is one of the most fascinating enzymes. It increases the rate of decarboxylation of its substrate orotidine 5 -mono-phosphate (OMP) (see Fig. 1) by 17 orders of magnitude. This rate acceleration is unmatched by other known enzymes [1]. Analyzing the mechanism of ODCase can therefore be an important step in understanding enzyme catalysis on a more general level. 

The mechanism of the enzymatic decarboxylation of orotidine 5 -mono-phosphate (OMP) to uridine 5 -monophosphate (UMP) (see Fig. 1) is an intriguing problem for which many solutions have been offered. Even before 1995 when Wolfenden and Radzicka declared OMP decarboxylase (ODCase) to be the most proficient enzyme [1], several different mechanisms had been proposed. Since that time, other mechanisms have been advocated. Curiously, the appearance of crystal structures for various wild-type and mutant ODCases has led not to a definitive picture of catalysis, but to even more conjecture and controversy concerning the mechanism. 

PRTase - phosphoribosyl transferase ODCase - OMP decarboxylase OMP - orotidine 5 -phosphate... 

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