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)

Abstract

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).

Keywords

Pyrimidine Purine Nucleoside Xanthine Allo 

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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

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