Thymidine Salvage Pathway in Normal and Leukemic Leukocytes with Effects of ATP on Enzyme Control

The enzymes of the "salvage" pathway for thymidine in normal and leukemic leukocytes separated on glass-bead-columns were studied. Levels of thymidine kinase activity in blast cells were high, but were low in granulocytes, normal and leukemic lymphocytes, and in RBC. Phosphatase and thymidine phosphorylase activity was high in granulocytes and in normal and leukemic lymphocytes, but became apparent in blast cells only in the absence of ATP. All the cells studied could phosphorylate TMP to some extent, but the amount of TTP formed depended greatly on the presence of an optimum ATP concentration. Without added ATP breakdown to thymine was at its peak, while phosphorylation of TMP was negligible. Excess ATP reduced or inhibited the activity of most of the enzymes, preventing both phosphorylation and breakdown. Concentrations of Mg equimolar with the ATP gave maximum TTP production, while inhibition by high ATP concentrations occurred despite equimolar Mg concentrations. Both TTP and thymine production ceased in the absence of Mg. Changes in ATP levels in cell loci may function in regulating thymidine metabolism.