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Purine Metabolism in Intact Cells from a Purine Nucleoside Phosphorylase Deficient Child

  • A. Cohen
  • J. Barankiewicz
  • A. Issekutz
  • E. W. Gelfand
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

Deficiencies of two subsequent enzymes in the purine degradation pathway, Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNP), result in immunodeficiency in children (1–3). PNP deficient patients accumulate large amounts of all four PNP substrates, inosine, deoxyinosine, guanosine and deoxyguanosine in their plasma and urine (4,5). Moreover, the total urinary purine excretion by PNP deficient patients is several fold higher than the equivalent uric acid excretion by normal children (4,5). This observation indicates that the purine salvage pathway in humans is remarkably active and that PNP does not serve merely as a degrading enzyme, but it may also play a role in the reutilization of purines. The tissue(s) responsible for reutilization of purine has not been identified. It has been suggested that purine reutilization represents a means by which purines are transported from the liver a tissue with active purine de novo biosynthesis, to be reutilized by peripheral tissue(s). Alternatively, it may be that purine reutilization is mainly an intracellular process since most tissues have both purine de novo and purine salvage pathways.

Keywords

Adenosine Deaminase Purine Metabolism Purine Nucleoside Phosphorylase Total Incorporation Subsequent Enzyme 
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.
    Giblett, E.R., Anderson, J.E., Cohen, F., Pollara, B., and Meurvissen, H.J. (1972). Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet 2:1067.PubMedCrossRefGoogle Scholar
  2. 2.
    Giblett, E.R., Ammann, A.J., Wara, D.W., Sandman, R., and Diamond, L.K. (1975). Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet 1:1010.PubMedCrossRefGoogle Scholar
  3. 3.
    Gelfand, E.W., Dosch, H.-M., Biggar, W.D. and Fox, I.H. (1978). Partial purine nucleoside Phosphorylase deficiency: Studies of lymphocyte function. J. Clin. Invest. 61:1071.PubMedCrossRefGoogle Scholar
  4. 4.
    Cohen, A., Doyle, D., Martin, D.W., Jr., and Ammann, A.J. (1976). Abnormal purine metabolism and purine overproduction in a patient deficient in purine nucleoside Phosphorylase. N. Engl. J. Med. 295:1449.PubMedCrossRefGoogle Scholar
  5. 5.
    Siegenbeek Van Heukelam, L.H., Akerman, J.W.W., Staal, G.J., De-Bruyn, C.H.M., Stoop, J.W., Zegers, B.J.M., Debree, P.K. and Wadman, S.K. (1977). A patient with purine nucleoside Phosphorylase deficiency: enzymological and metabolic aspects. Clin. Chim. Acta. 74:271.CrossRefGoogle Scholar
  6. 6.
    Cohen, A., Lee, J.W.W., Dosch, H.M., and Gelfand, E.W. (1980). The expression of deoxyguanosine toxicity in T lymphocytes at different stages of maturation. J. Immunol. 125:1578.PubMedGoogle Scholar
  7. 7.
    Carson, D.A., Kaye, J., and Seegmiller, J.E. (1977). Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside Phosphorylase deficiency: Possible role of nucleoside kinase(s), P.N.A.S. 74:5677.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • A. Cohen
    • 1
  • J. Barankiewicz
    • 1
  • A. Issekutz
    • 2
  • E. W. Gelfand
    • 1
  1. 1.Division of Immunology, Research InstituteThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Department of PediatricsDalhousie UniversityHalifaxCanada

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