On the biosynthesis of uric acid from glycine-N 15 in primary and secondary polycythemia

Abstract

1. 1. The rate and magnitude of glycine-N 15 incorporation into urinary uric acid was studied in two cases of polycythemia vera and two cases of polycythemia secondary to congenital heart anomaly. 2. 2. It was demonstrated, by the magnitude of cumulative isotope labeling of urinary uric acid, that the occurrence of hyperuricemia and/or hyperuricosuria in some cases of polycythemia is attributable to overproduction of uric acid, as has long been suspected. 3. 3. The rate curves of glycine-N 15 incorporation into uric acid in polycythemia vera revealed slow, progressive enrichment of isotope, with peak abundance at the end of the second week after glycine-N 15 ingestion. The predominant route of uric acid biosynthesis in polycythemia vera therefore does not involve rapid, “shunt” metabolic pathways. The time relationships, however, are consistent with conversion of glycine into the purine components of intracellular nucleic acids, and subsequent biotransformation into uric acid. Evidence was obtained of diversion of excessive quantities of glycine into these metabolic channels, presumably to meet the excessive requirements of augmented hemopoietic activity. 4. 4. The rate curves of glycine-N 15 incorporation into urinary uric acid in secondary polycythemia were found to differ significantly from those in polycythemia vera, at least in the late phases examined. These differences may be related to the excessive production of cells of the myeloid series associated with the late phases of the myeloproliferative disorders. 5. 5. The sharp contrast between the rapid peak of glycine-N 15 incorporation into uric acid in primary gout and the slow peak in secondary gout indicates that, despite the similarities in clinical manifestations and therapeutic responses, the predominant pathways of uric acid biosynthesis in primary and secondary gout are different, and hence they have a different pathogenesis. 6. 6. It is not possible, from the rate and cumulative curves of glycine-N 15 incorporation into uric acid, to determine whether or not clinically overt gout has developed or will develop. This apparent paradox, which applies to latent and manifest primary and secondary gout, is discussed. 7. 7. The urinary excretion of purine bases other than uric acid was studied in primary and secondary polycythemia. Excessive excretion of 8-hydroxy-7-methylguanine, a newly discovered purine demonstrated by glycine-N 15 incorporation to be an endogenous metabolite, was found in polycythemia vera.