Acidity constants orotidine

Pigs given allopurinol showed an increase in urinary orotic acid and orotidine excretion from a mean of 5 to a mean of 50 mg/2 hours. Although the dose of allopurinol was constant the levels of orotic acid and orotidine fell gradually from their initial peak. When the drug was stopped levels returned rapidly to normal. These results are similar to those obtained in rat and man (I), where this effect has been attributed to inhibition of the enzyme orotidylic decarboxylase (2). 

In the case of orotic acid, nonenzymatic decarboxylation proceeds with a half-time (ti/2) of about 2.45 X 10 s near pH 7 at room temperature, as indicated by reactions in quartz tubes at elevated temperatures Orotidine 5 -phosphate decarboxylase thus appears to be an extremely proficient enzyme which enhances the reaction rate by a factor of 10 . They estimate the transition state form of the substrate has a dissociation constant that is less than 5 x 10 M. 

The first reaction is catalysed by orotate phosphoribosyltransferase (orotidine 5 -phosphate pyrophosphate phosphoribosyltransferase, EC 2.4.2.10) which is readily reversible. The equilibrium constant for the forward reaction [109] is about 0.1. The reaction is specific for orotate (the enzyme usually does not accept uracil) and some synthetic analogues of orotic acid (Chapter 6). Orotate phosphoribosyltransferase activity was found in many animal tissues [110] and there are several phosphoribosyl-transferases of broad specifity which are distinct from the enzyme involved in the orotate pathway [111-113]. 

Orotidine 5 -phosphate pyrophosphoiylase has been found in liver and yeast. The enzyme is specific for orotic acid and catalyzes the reversible reaction (16A). The equilibrium constant is approximately 0.1 but the reaction is pulled in the direction of ribotide synthesis by the irreversible decarboxylation of orotidine 5 -phosphate by orotidine 5 -phosphate decarboxylase [Eq. (16B)] (Sa, 48). 

Orotidine and its derivatives play an important role as intermediates in the metabolism of pyrimidine-nucleotides [91]. Its structure is shown in Figure 8 (top, left) it is closely related to uridine (see Figure 1), but due to the (C6)-carboxylate group it exists in solution mainly in the syn conformation [89]. The (C6)COOH group is very acidic for aqueous solution it was estimated that pATa = 0.5 0.3 [92]. Consequently, the stability constants of the orotidinate (Or ) complexes of Mg ", Cu ", and Zn " (only these metal ions have been studied [92]) are somewhat below of those measured for the corresponding M(Ac) complexes (see Table 1, column 7). There is no evidence for any significant chelate formation in aqueous solution [92]. Therefore, one may assume that all this also holds for the Cd(Or) complex, which gives as an estimate for its stability log cd(Or) = 1-0 0-3-... 

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