The Molecular Basis for the Effects of Allopurinol on Pyrimidine Metabolism
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 . Somewhat later this ribonucleoside was synthesized chemically, and enzymatically by purine nucleoside phosphorylase, and was identified as 1-ribosylallopurinol (Fig. 1, I). 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).
KeywordsPurine Nucleoside Phosphorylase Pyrimidine Metabolism Uridine Phosphorylase Dose Allopurinol Nucleic Acid Fraction
Unable to display preview. Download preview PDF.
- 9.J.A. Fyfe, R.L. Miller & T.A. Krenitsky (1973) J. Biol. Chem., in press.Google Scholar
- 10.D.J. Nelson, unpublished.Google Scholar
- 11.D.J. Nelson, C.J.L. Bugge, H.C. Krasny & G.B. Elion (1973) Biochem. Pharmacol., in press.Google Scholar
- 12.D.J. Nelson, C.J.L. Bugge, H.C. Krasny & G.B. Elion (1973) Fed. Proc., 32: 511.Google Scholar
- 13.N.L.R. Bucher & M.N. Swaffield (1966) B.B.A., 129: 445.Google Scholar