Orotic acid as a precusor of pyrimidines in the rat.

It was demonstrated by Richardson in 1936 (1) that uracil and guanine were essential for the growth of certain bacteria. Later several investigators found that purines and pyrimidines and corresponding nucleotides are of importance for the metabolism of different microorganisms. Snell and Mitchell (2) established the fact that guanine, adenine, uracil, and thymine may be limiting factors of growth for lactic acid bacteria. In 1944 Loring and Pierce (3), working with pyrimidine-deficient mutants of Neurospora, found that erotic acid (uracil-4-carboxylic acid) and uracil had about the same growth-promoting effect, but that uridine and uridylic acid were 10 to 60 times more active. Simultaneously Rogers (4) reported that the growth of certain streptococci was stimulated to an equal degree by uracil and erotic acid, and Chattaway (5) observed that erotic acid was the only pyrimidine derivative that could replace the effect of liver extract on Lactobacillus ca-sei E. These results indicated that erotic acid might be an intermediate in pyrimidine metabolism. Mitchell and Houlahan (6) proposed that oxalacetic, aminofumaric, and erotic acids may be intermediates in the synthesis of uridine and that the coupling with ribose occurred prior to the formation of the pyrimidine ring. Orotic acid was discovered in milk in 1905 by Biscaro and Belloni (7). Recently it has been found to be produced in large amounts by certain Neurospora mutants. Genetic analysis of these strains led Mitchell, Houlahan, and Nyc (8) to the conclusion that erotic acid is not a normal intermediate in the biosynthesis of pyrimidines in Neurospora but is formed as a by-product in a side reaction. The occurrence in milk might be interpreted in a similar way. In order to investigate this problem in animals, we have administered erotic acid containing N16 to rats.