The roles of uridine-cytidine kinase and CTP synthetase in the synthesis of CTP in malignant human T-lymphocytic cells.
The pattern of incorporation of [14C]uridine showed that in MOLT-3 cells an increased proportion of CTP was synthesized via CTP synthetase, compared to proliferating normal human T lymphocytes at a physiological concentration of cytidine (< 0.5 microM). Furthermore, in the proliferating normal human T lymphocytes similar patterns of incorporation of [14C]uridine were observed in the presence of the physiological concentration of cytidine and after addition of 2 microM of cytidine. In contrast, in the MOLT-3 cells after addition of 2 microM of cytidine the proportion of CTP synthesized by conversion of UTP into CTP was substantially decreased, whereas the salvage of cytidine was proportionally increased. We conclude that the reutilization of uridine is a preferred route in the synthesis of CTP for MOLT-3 cells at physiological concentrations of uridine and cytidine, whereas in proliferating normal human T lymphocytes CTP is largely synthesized through reutilization of cytidine. This difference in salvage of pyrimidine ribonucleosides may be exploited for selective chemotherapy.
van den Berg
A A
AA
Academic Medical Center, Division of Pediatrics, Amsterdam, The Netherlands.
van Lenthe
H
H
Busch
S
S
de Korte
D
D
van Kuilenburg
A B
AB
van Gennip
A H
AH
D002250:Carbon Radioisotopes; D019731:Carbon-Nitrogen Ligases; D002460:Cell Line; D003570:Cytidine Triphosphate / Q000096:biosynthesis*; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008954:Models, Biological; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D013601:T-Lymphocytes / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism; D014541:Uridine Kinase / Q000378:metabolism*
D002250:Carbon Radioisotopes; D003570:Cytidine Triphosphate; D014541:Uridine Kinase; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase; D014529:Uridine