Pyrimidine metabolism in hereditary erythrocyte pyrimidine 5' nucleotidase deficiency.

A patient with hereditary erythrocyte pyrimidine 5' nucleotidase deficiency was studied to determine the mechanism of accumulation of erythrocyte pyrimidine nucleotides. Estimates of the rate of degradation of uridine nucleotides to diffusable products imply that the high levels found in these patients could not be sustained from the degradative pathways alone. Active synthesis of uridine nucleotides was found to occur in erythrocytes from both patient and control blood samples when either uridine or orotate was used as a substrate. The circulating levels of uridine in the blood are such that sufficient nucleotides to account for the high levels seen in these patients could accumulate in the erythrocytes from biosynthetic pathways alone, quite apart from the contribution from degradation of residual ribosomal RNA. This provides scope for new therapeutic approaches; treatment with allopurinol, however, was found to result in an increase, rather than a decrease, in erythrocyte pyrimidine nucleotides.