ALLOPURINOL-1-RIBOSIDE FORMATION AND HGPRT-DEFICIENCY: 170

Allopurinol-1-riboside has been thought to be synthesized in vivo rather directly by purine nucleoside phosphorylase(PNP) than indirectly via the ribotide by hypoxanthine guanine phosphoribosyl-transferase(HGPRT). Consequently the lack of allopurinol-1-riboside formation in HGPRT-deficiency has been attributed to competitive inhibition of PNP by increased hypoxanthine levels(Elion, Handb.Exp.Pharm.51). Having demonstrated elevated excretion of allopurinol-1-riboside in PNP-deficiency we studied the influence of hypoxantbine on allopurinol-1-riboside formation in healthy volunteers and a patient with partial(5% residual activity) HGPRT-deficiency. Allopurinol was given as a single dose of 5mmol, the volunteers received additionally 7,5mmol of different purines. The volunteers shoved a reciprocal relationship between allopurinol-1-riboside excretion(0,615-0,034 mmol) per 24hrs and hypoxanthine excretion(0,082-1,22mmol) during the first 5hrs following allopurinol and purine intake - the period of allopurinol-1-riboside formation. The corresponding values of our patient were 0,014mmol allopurinol-1-riboside and 0,24mmol hypoxanthine. These data indicate that the very low excretion of allopurinol-1-riboside in HGPRT-deficiency must be attributed to the enzyme defect itself as it cannot be explained by the moderate elevation of hypoxanthine formation.