Thymidine and thymine incorporation into deoxyribonucleic acid: inhibition and repression by uridine of thymidine phosphorylase of Escherichia coli.
Thymidine is poorly incorporated into deoxyribonucleic acid (DNA) of Escherichia coli. Its incorporation is greatly increased by uridine, which acts in two ways. Primarily, uridine competitively inhibits thymidine phosphorylase (E.C.2.4.4), and thereby prevents the degradation of thymidine to thymine which is not incorporated into normally growing E. coli. Uridine also inhibits induction of the enzyme by thymidine. It prevents the actual inducer, probably a deoxyribose phosphate, from being formed rather than competing for a site on the repressor. The inhibition of thymidine phosphorylase by uridine also accounts for inhibition by uracil compounds of thymine incorporation into thymine-requiring mutants. Deoxyadenosine also increases the incorporation of thymidine, by competitively inhibiting thymidine phosphorylase. Deoxyadenosine induces the enzyme, in contrast to uridine. But this is offset by a transfer of deoxyribose from deoxyadenosine to thymine. Thus, deoxyadenosine permits incorporation of thymine into DNA, even in cells induced for thymidine phosphorylase. This incorporation of thymine in the presence of deoxyadenosine did not occur in a thymidine phosphorylase-negative mutant; thus, the utilization of thymine seems to proceed by way of thymidine phosphorylase, followed by thymidine kinase. These results are consistent with the data of others in suggesting that wild-type E. coli cells fail to utilize thymine because they lack a pool of deoxyribose phosphates, the latter being necessary for conversion of thymine to thymidine by thymidine phosphorylase.
D004269:DNA, Bacterial / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D008025:Ligases / Q000378:metabolism; D009705:Nucleosides / Q000494:pharmacology; D010428:Pentosephosphates / Q000096:biosynthesis; D010429:Pentoses / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism* / Q000494:pharmacology; D013937:Thymidine Kinase / Q000378:metabolism; D013941:Thymine / Q000378:metabolism*; D014316:Tritium; D014498:Uracil / Q000494:pharmacology; D014529:Uridine / Q000494:pharmacology*
D004269:DNA, Bacterial; D009705:Nucleosides; D010428:Pentosephosphates; D010429:Pentoses; D014316:Tritium; D014498:Uracil; D005964:Glucosyltransferases; D013937:Thymidine Kinase; D008025:Ligases; D013941:Thymine; D013936:Thymidine; D014529:Uridine