Regulation of phosphoribosylpyrophosphate synthetase by endogenous purine and pyrimidine compounds and synthetic analogs in normal and leukemic white blood cells.
Phosphoribosylpyrophosphate (PRPP) is essential for the formation of both purine and pyrimidine nucleotides as well as for the active nucleotide form of some chemotherapeutic agents. The formation of PRPP is catalyzed by by enzyme PRPP synthetase, and many different compounds are known to affect the activity of this enzyme. This report examines the effects of endogenous purine and pyrimidine nucleotides, nucleosides, and several analogs of these compounds on the activity of PRPP synthetase from different types of normal and leukemic white blood cells (i.e. normal lymphocytes, normal granulocytes, phytohemagglutinin-stimulated lymphocytes, and acute and chronic leukemic cells). Our results show that the effect varied with each individual compound, and the magnitude of the effect was dependent on the source of the enzyme. Since it appears possible to differentially affect PRPP synthetase activity from the different types of leukemic cells, this enzyme may be a potential target site in the chemotherapy of leukemia.
D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000201:enzymology*; D007962:Leukocytes / Q000201:enzymology*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011687:Purines / Q000502:physiology*; D011743:Pyrimidines / Q000502:physiology*; D012268:Ribose-Phosphate Pyrophosphokinase / Q000037:antagonists & inhibitors*
D011687:Purines; D011743:Pyrimidines; D010770:Phosphotransferases; D012268:Ribose-Phosphate Pyrophosphokinase