Orotic acid, a precursor of pyrimidines in the rat.

In recent years erotic acid (uracil-4-carboxylic acid) has been found to be essential for the growth of some microorganisms;l some pyrimidine-requiring Neurospora mutants were found to grow equally well with uracil and erotic acid2 and some mutants have been found to produce erotic acid.3 It has been suggested that erotic acid is a by-product in the biosynthesis of pyrimidines in Neurospora.s In order to investigate the metabolism of erotic acid in the rat we have synthesized erotic acid* containing 6.06 atom per cent excess N15. This acid was injected into rats, 12.5 mg. per 100 gm. of body weight, twice daily for 3 days. From the pooled livers the polynucleotides were prepared and the ribosides isolated. The cytidine and uridine were found to contain respectively 0.872 and 1.133 atom per cent excess N15; i.e., a dilution of only 5.4and 6.9-fold. The purine ribosides, adenine and guanine from DNA and the proteins contained only insignificant amounts of N15. Plentl and Schoenheimer5 have found that neither uracil nor thymine administered to rats was utilized for the synthesis of polynucleotides. Our results prove that the injected erotic acid was utilized in the biosynthesis of both uracil and cytosine. A detailed report will appear later.