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Increases in Purine Excretion and Rate of Synthesis by Drugs Inhibiting IMP Dehydrogenase or Adenylosuccinate Synthetase Activities

  • R. C. Willis
  • J. E. Seegmiller
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 122B)

Abstract

Hershfield reported an assay system devoid of hypoxanthine for evaluating the rate of purine synthesis de novo based on rates of [14C]-formate incorporation into intracellular purine components of lymphoblasts and into purines excreted into the culture medium. Using this system normal and in vitro selected, biochemically-characterized HPRT* deficient lines were found to have similar rates of total purine synthesis; however, these cell lines differed markedly in the excretion of newly-formed purine into the medium (1,2).

Keywords

Mycophenolic Acid Purine Nucleoside Purine Nucleoside Phosphorylase Purine Synthesis Inosine Monophosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    M.S. Hershfield and J.E. Seegmiller, Regulation of de novo purine synthesis in human lymphoblasts. J. Biol. Chem. 252: 6002 (1977).PubMedGoogle Scholar
  2. 2.
    R.C. Willis, D.A. Carson, and J.E. Seegmiller, Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line. Proc.Natl.Acad.Sci.USA 75: 3042 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    L.H. Siegenbeek van Heukelom, J.W.N. Akkerman, G.E.J. Staal, C.H.M.M. DeBruyn, J.W. Stoop, B.J.M. Zegers, P.K. deBreu and S.K. Wadson, A patient with purine nucleoside Phosphorylase deficiency: enzymological and metabolic aspects. Clin. Chim. Acta. 74: 271 (1977).CrossRefGoogle Scholar
  4. 4.
    M.A. Becker, K.O. Raivio, and J.E. Seegmiller, Synthesis of phosphoribosylpyrophosphate in mammalian cells in.: “Advances in Enzymology”, A. Mesiter, ed., John Wiley & Sons, Inc. (1979).Google Scholar
  5. 5.
    A.J. Nelson, L.M. Rose, and L.L. Bennett, Jr., Mechanism of action of 2-amino-1,3,4-thiadiazole (NSC 4728). Cancer Res. 37: 182 (1977).PubMedGoogle Scholar
  6. 6.
    R.C. Willis and J.E. Seegmiller, Defining serum requirements of culture media for use in studies of physiological effects of various genetic diseases. in: “Monographs in Human Genetics”, O. Sperling, A. deVries and P. Tiqva, ed., S. Karger, Basel (1978)Google Scholar
  7. 7.
    W.N. Kelley, E.W. Holmes, and M.B. Van Der Weyden, Current concepts on the regulation of purine biosynthesis de novo in man. Arth. & Rheum. 18: 673 (1975).CrossRefGoogle Scholar
  8. 8.
    J.C. Graff and P.G.W. Plagemann, Alanosine toxicity in Novikoff rat hepatoma cells due to inhibition of the conversion of inosine monophosphate to adenosine monophosphate. Cancer Res. 36: 1428 (1976).PubMedGoogle Scholar
  9. 9.
    J.K. Lowe, L. Brox, and J.F. Henderson, Consequences of inhibition of guanine nucleotide synthesis by mycophenolic acid and virazole. Cancer Res. 37: 736 (1977).PubMedGoogle Scholar
  10. 10.
    B. Ullman, S.M. Clift, A. Cohen, L.J. Gudas, B.B. Levinson, M.A. Wormsted and D.W. Martin, Jr., Abnormal regulation of de novo purine synthesis and purine salvage in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase. J. Cell. Physiol. 99: 139 (1979).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • R. C. Willis
    • 1
  • J. E. Seegmiller
    • 1
  1. 1.University of California San DiegoLa JollaUSA

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