Pyrimidine Orotidylic pyrophosphorylase

As early as 1949, it was demonstrated that injected or " C-labeled orotic acid was readily incorporated into DNA and RNA of mammalian tissue, indicating that orotic acid is a precursor of nucleic acid pyrimidine. The next step in pyrimidine biosynthesis is the formation of the first nucleotide in the sequence. It involves the reaction between ribosyl pyrophosphate and orotic acid to yield 5 -orotidylic acid the reaction is catalyzed by orotidylic pyrophosphorylase. Thus, the first steps of pyrimidine biosynthesis differ from the early steps of purine biosynthesis in at least two ways. Orotic acid, instead of being synthesized atom by atom as is the case for the purine ring, is made from the condensation of rather large molecules, namely, carbamyl phosphate and aspartic acid. Furthermore, all the steps of purine biosynthesis occur at the level of the nucleotide, but the the pyrimidine ring is closed at the level of the base. 

The formation of the first nucleotide in the pyrimidine sequence, orotidylic acid (orotidine 5 -phosphate), was accomplished by the reaction of 5-phosphoribosyl-l-pyrophosphate (PRPP) with orotic acid 83) (Fig. 22). Other pyrimidines and carbamylaspartic acid did not react with PRPP in the presence of the enzyme, which has been named orotidine 5 -phosphate pyrophosphorylase. Several purine analogs, e.g., 6-uracilsulfonic acid, 6-uracil methyl sulfone, which inhibited the growth of several organisms (S78, 379), probably inhibited the formation of orotidylic acid. 

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