Synthesis of Purine Nucleotides in Human and Leukemic Cells. Interaction of 6-Mercaptopurine and Allopurinol

  • W. Wilmanns
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 41A)


In proliferating cells purine nucleotides — necessary for DNA- and RNA-synthesis — can be formed by incorporation of small precursors (de novo pathway) and by utilisation of free purin bases (salvage pathway). The most important reactions of both metabolic pathways are demonstrated in figure 1. The first reaction of the de-novo pathway — the formation of phosphoribosylamine from glutamine and phosphoribosylpyrophosphate (PRPP) by the enzyme PRPPamidotransferase — is the target of a negative feed back control mechanism by the endproducts IMP,GMP and AMP (1).


Xanthine Oxidase Acute Leukemia Purine Nucleotide Purine Synthesis Purine Ring 
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  1. 1.
    CASKEY, C. T., D. M. ASHTON, and J.B. WYNGAARDEN. (1964) The enzymology of feedback inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides. J.Biol.Chem. 239: 2570PubMedGoogle Scholar
  2. 2.
    DAVIDSON, J. D., and T. S. WINTER: Purine nucleotide Pyrophosphorylase in 6-Me rcaptopurine-sensitive and resistant human leucemias. Cancer Res. 24: 261 (1964)PubMedGoogle Scholar
  3. 3.
    ELION, G. B., S. GALLAHAN, R. W. RUNDLES and G. H. HITCHINGS: Relationship between metabolic fates and antitumor activities of thiopurines. Canc. Res. 23 S. 1207–1217 (1963)Google Scholar
  4. 4.
    GOTS, J. S., and J. GOLDSTEIN: Specific action of adenine as a feed back inhibitor of purine biosynthesis. Science 130, 622 (1959)PubMedCrossRefGoogle Scholar
  5. 5.
    GOTS, J. S., and E. G. GOLLUP: Purine analogs as feedback inhibitors.Proc.Soc. exp.Biol. (N.Y.)101: 641, (1959)Google Scholar
  6. 6.
    HENDERSON, J.F.: Feedback inhibition of purine biosynthesis in ascites tumor cells by purine analogues. Biochem. Pharmacol. 12, 551 (1963)PubMedCrossRefGoogle Scholar
  7. 7.
    LE PAGE, G. A. and M. JONES: Purinethiols as feedback inhibitors of purine synthesis in ascites tumor cells. Cancer Res. 21, 642 (1961)Google Scholar
  8. 8.
    LUKENS, L. N., and K. A. HERRLINGTON: Enzymatic formation of 6-Mercaptopurine ribotide.Biochim.biophys. Acta (Amst.)24: 432 (1957)Google Scholar
  9. 9.
    MC COLLISTER, R. J., W. R. GILBERT jr., D. M. ASHTON, and J. B. WYNGAARDEN: Pseudofeedback inhibition of purine synthesis by 6-Mercaptopurine ribonucleotide and other purine analogues. J.biol.Chem. 239: 1560 (1964)Google Scholar
  10. 10.
    MC COLLISTER, R. J. and J. B. WYNGAARDEN: Pseudofeedback of purine synthesis by 6-Mercaptopurine and other purine 41, 1383 (1962)Google Scholar
  11. 11.
    UNGER, K. W., and R. SILBER: Studies on the formate activating enzyme:Kinetics of 6-Mercaptopurine inhibition and stabilisation of the enzyme.Biochim.biophys.Acta (Amst.) 89, 167 (1964).Google Scholar
  12. 12.
    WILMANNS, W.: Formiat-Aktivierung und de novo-Synthese von Purin-Nucleotiden in Leukämiezellen und ihre therapeutische Beeinflussung durch 6-Mercaptopurin. Zschr. ges.exp. Med. 147, 154 (1968)Google Scholar

Copyright information

© Plenum Press, New York 1974

Authors and Affiliations

  • W. Wilmanns
    • 1
  1. 1.Department of Internal Medicine IIUniversity ClinicTuebingenGermany

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