Uracil Metabolism in Tadpoles during Thyroxine-induced Metamorphosis.

Previous work in this laboratory (1) has shown that an increase in carbamyl phosphate synthetase activity in the livers of thyroxine-treated tadpoles is the result of protein synthesis de 1u)vo. This induction of the synthesis of a specific enzyme protein by thyroxine was found to be inhibited by chloramphenicol and thiouracil (2). A subsequent survey (3) of several purine and pyrimidine derivatives showed that, of the compounds tested, 2-thiouracil, 2,6-dithiouracil, 2,4-dithiouracil, and 2,4-dihydroxypyrimidine were potent inhibitors of carbamyl phosphate synthetase synthesis. While thiourea was also inhibitory, its effect was different from that of the pyrimidine analogues in that it was not inhibitory during the early phases of the induction. It was postulated that the inhibition by thiouracil and certain related compounds was due to formation of a “faulty ribonucleic acid” which could no longer participate in the synthesis of carbamyl phosphate synthetase. Evidence for the incorporation of thiouracil into ribonucleic acid was presented in support of this hypothesis (3). Uracil at about the same molarity as thiouracil was able to reverse partially the thiouracil inhibition of synthesis of carbamyl phosphate synthetase. Because uracil seemed to affect the latent period before thyroxine stimulation of carbamyl phosphate synthetase formation was observed, and no direct combination or reaction of thiouracil and thyroxine could be demonstrated, it was suggested that thyroxine might affect uracil metabolism. In this paper additional studies of the influence of pyrimidines on carbamyl phosphate synthetase synthesis in tadpoles have been carried out. The results indicate that uracil, uridine, and erotic acid enhance the stimulating effect of thyroxine. The relationship between uracil metabolism and thyroxine treatment was also examined.