Studies in pyrimidine metabolism

Abstract

By partial hydrolysis of yeast nucleic acid, preparations containing pyrimidines as the only nitrogenous constituents were prepared and administered to rabbits. Uracil nucleoside when administered per os, subcutaneously or intraperitoneally caused an increased excretion of urea often much more than enough to account for the nitrogen administered. The undetermined nitrogen (the difference between the total nitrogen and the urea nitrogen) was always increased. A part of the increase in the undetermined nitrogen was due to the excretion of free uracil which was isolated in pure crystalline form. As much as 20 per cent. of the uracil fed as the nucleoside was recovered free in the urine. When a mixture of cytosine and uracil nucleosides was administered to rabbits, there was an increased excretion of urea and usually no increase in the undetermined nitrogen. Uracil was isolated from the urine of one animal and was barely detected by a color reaction in another. No increase of creatine, creatinine, or purines was detected after feeding either preparation. Not even a color reaction for pyrimidines was obtained by using the same procedures on the urine obtained after feeding yeast nucleic acid. Mendel and Myers were unable to find a trace of pyrimidine in the urine after feeding yeast nucleic acid but found that uracil, when fed, was excreted unchanged. Taken together, the data show that increasing quantities of uracil appear in the urine as simpler complexes containing the uracil group are fed. The conclusion may therefore be drawn (at least in respect to uracil), that, in the metabolism of yeast nucleic acid before the pyrimidine is liberated and even before the nucleoside is formed, the pyrimidine is altered in such a way that it may be further broken down and its nitrogen converted into urea.