The Molecular Basis for the Effects of Allopurinol on Pyrimidine Metabolism

  • James A. Fyfe
  • Donald J. Nelson
  • George H. Hitchings
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 41 B)


Investigations undertaken early in the course of clinical studies of allopurinol established the predominance of oxipurinol (alloxanthine) among its metabolites. However, one patient to whom 14C-allopurinol had been given excreted a significant amount of a presumptive allopurinol ribonucleoside [1]. Somewhat later this ribonucleoside was synthesized chemically, and enzymatically by purine nucleoside phosphorylase, and was identified as 1-ribosylallopurinol (Fig. 1, I)[2]. With oxipurinol as substrate the corresponding 1-ribosyloxipurinol (Fig. 1, II) was obtained, and by using uridine phosphorylase a third ribonucleoside, oxipurinol-7-ribonucleoside was prepared. Meanwhile a third metabolite had been isolated from the urine of treated patients, and the availability of reference substances made it possible to identify this as 7-ribosyl-oxipurinol (Fig. 1, III).


Purine Nucleoside Phosphorylase Pyrimidine Metabolism Uridine Phosphorylase Dose Allopurinol Nucleic Acid Fraction 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G.B. Elion, A. Kovensky, G.H. Hitchings, E. Metz & R.W. Rundles (1966) Biochem. Pharmacol., 15: 863.PubMedCrossRefGoogle Scholar
  2. 2.
    T.A. Krenitsky, G.B. Elion, R.A. Strelitz & G.H. Hitchings (1967) J. Biol. Chem., 242: 2675.PubMedGoogle Scholar
  3. 3.
    W.N. Kelley & J.B. Wyngaarden (1970) J. Clin. Invest., 49: 602.PubMedCrossRefGoogle Scholar
  4. 4.
    R.M. Fox, D. Royse-Smith & W.J. O’Sullivan (1970) Science, 168: 861.PubMedCrossRefGoogle Scholar
  5. 5.
    W.N. Kelley & T.D. Beardmore (1970) Science, 169: 388.PubMedCrossRefGoogle Scholar
  6. 6.
    R.M. Fox, M.H. Wood & W.J. O’Sullivan (1971) J. Clin. Invest., 50: 1050.PubMedCrossRefGoogle Scholar
  7. 7.
    T.D. Beardmore & W.N. Kelley (1971) J. Lab. clin. Med., 78: 696.PubMedGoogle Scholar
  8. 8.
    W.N. Kelley, T.D. Beardmore, I.H. Fox & J.C. Meade (1971) Biochem. Pharmacol., 20: 1471PubMedCrossRefGoogle Scholar
  9. 9.
    J.A. Fyfe, R.L. Miller & T.A. Krenitsky (1973) J. Biol. Chem., in press.Google Scholar
  10. 10.
    D.J. Nelson, unpublished.Google Scholar
  11. 11.
    D.J. Nelson, C.J.L. Bugge, H.C. Krasny & G.B. Elion (1973) Biochem. Pharmacol., in press.Google Scholar
  12. 12.
    D.J. Nelson, C.J.L. Bugge, H.C. Krasny & G.B. Elion (1973) Fed. Proc., 32: 511.Google Scholar
  13. 13.
    N.L.R. Bucher & M.N. Swaffield (1966) B.B.A., 129: 445.Google Scholar
  14. 14.
    G.B. Elion, Ts’ai-Fan Yü, A.B. Gutman & G.H. Hitchings (1968) Am. J. Med., 45: 69.PubMedCrossRefGoogle Scholar
  15. 15.
    T.D. Beardmore, J.S. Cashman & W.N. Kelley (1972) J. Clin. Invest., 51: 1823.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1974

Authors and Affiliations

  • James A. Fyfe
    • 1
  • Donald J. Nelson
    • 1
  • George H. Hitchings
    • 1
  1. 1.Wellcome Research LaboratoriesResearch Triangle ParkUSA

Personalised recommendations