Metabolism of 2-Thiouracil in Pyrimidine Pathways Leading to Nucleotide Synthesis

The present results demonstrate that the antithyroid drug 2-thiouracil can be metabolized in animal tissues to the corresponding nucleotide by at least two pathways. In one pathway, uridine phosphorylase catalyzes the reversible conversion of thiouracil to thiouridine and further metabolism of 2-thiouridine to thio-UMP is catalyzed by uridine kinase. In the other pathway, thiouracil is converted to thiouridine by thymidine phosphorylase, then to thio-UMP by uridine kinase. Although thymidine phosphorylase can also form 2-thiodeoxyuridine, further metabolism of this compound by thymidine kinase to a deoxyribonucleotide does not appear to occur.