Studies on the Physiology of Pyrimidines. The Intermediary Metabolism of Uracil.

In an earlier paper 1 experiments were reported which showed that uracil and thymine, when fed in small amounts to dogs, are metabolized to urea. It was also shown that thymine glycol which is obtained on oxidation of thymine in vitro 2 is probably an intermediate step in the oxidation of this pyrimidine in the animal body. These results led the writer to investigate the fate of isobarbituric and isodialuric acids which are oxidation products of uracil in vitro 3 as possible intermediate metabolic products of uracil.

Steudel 4 reported feeding experiments with these two substances. He found that they were apparently completely oxidized.

Isobarbituric acid and isodialuric acid were fed to dogs maintained on a nitrogen equilibrium. In every case when isodialuric acid was administered, there was an increase in the urea output, suggesting that this substance was metabolized. In the case of isobarbituric acid, the increase in the urea output after feeding the substance was not as pronounced as after administering isodialuric acid. This may have been due to a lesser absorption of isobarbituric acid on account of its being less soluble.

These experiments seem to indicate that in the metabolism of uracil we are dealing with an oxidation resembling that in. vitro as follows : Uracil → Isobarbituric acid → Isodialuric acid → urea + 3 C-atom compound.

In the course of these experiments we have observed a peculiar effect of these substances on the sulfur metabolism of the dogs. We found a distinct decrease in the output of inorganic sulfur on the day after feeding these pyrimidines. In some cases this decrease amounted to one-half of the amount ordinarily excreted. The writer is investigating this point further.