Orotidylate carboxylase

In reversal experiments using the human B-cell line (RPMI 8422), pyrazofurin inhibited cell growth at a concentration of 10 M. This PF effect was completely reversed with the addition of 10 M to 10 M of uridine or cytidine but not by orotic acid or orotidine. This is additional confirmation of the assumption that the site of inhibition in the biosynthesis of pyrimidine nucleotides is at the site of orotidylic carboxylase ... 

Many potent pyrimidine antagonists have also been obtained by isosteric replacement in the heterocyclic ring. Oxonic acid (Fig. 12) an analogue of orotic acid, prevents the conversion of the latter to orotidylic acid (Fig. 2). A later stage of pyrimidine biosynthesis, the decarboxylation of orotidylic acid to form uridylic acid (Fig. 2) is strongly inhibited by 6-azauracil (Fig. 12 this chemical should be correctly termed 4-azauracil). The riboside of 6-azainacil acts on the same pathways as the base, but its inhibition of the orotidylate carboxylase enzyme is some 20 times more potent... 

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See also in sourсe #XX -- [ ]

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