Depletion of Erythrocyte Phosphoribosylpyrophosphate in Man

Abstract

Allopurinol, a potent inhibitor of xanthine oxidase, is widely used for the treatment of hyperuricemia. When this drug was given to nine patients with gout, the concentration of phosphoribosylpyrophosphate (PRPP) in red cells was reduced significantly (p<0.01). Studies in vivo and in vitro showed that this depletion of PRPP results from the enzymatic conversion of allopurinol to allopurinol ribonucleotide, a process that consumes PRPP. The findings that allopurinol depletes PRPP and is apparently converted to its ribonucleotide in vivo suggest that this widely used drug may have a variety of biochemical effects in addition to xanthine oxidase inhibition. The observed changes provide several likely mechanisms to account for the previously documented inhibitory effect of allopurinol on purine synthesis de novo.