Fate of Oxypurines

In view of the obvious relationship between high uric acid levels and gout there has been a great deal of interest in hyperuricemia, and relatively little consideration has been given to a possible significance of hypouricemia. Studies have revealed, however, that in addition to the greatly discussed hyperuricemias there exist a certain small but real number of individuals whose uric acid levels run from a third to a sixth of the normal value (E7, F6). 

The serum uric acid pool and the amount of uric acid excreted are dependent upon many physiological factors. One of the more obvious of these is kidney function. About 60 years ago, Leathes (L5) noted that during work there was a decrease in urinary uric acid excretion coupled with an apparent increase in excretion of other purine bases. He felt that 

Decrease in label of urinary uric acid with time. The pool size can be calculated from the y intercept and the daUy turnover (fc) calculated from the equation k = l/t In A/(.A-X), in which A and X are isotope excess at ta and t, respectively. [From (G2).] 

There have been reports in the literature of hypouricemia coincident with specific inborn metabolic errors, but many of these cases are attributable to defects in the kidney leading to failure of renal tubular reabsorption. It was mentioned above that the excretion of uric acid by the Dalmatian coach hound can be attributed to such a mechanism (Fll). Similarly, the hypouricemia found in the Fanconi syndrome (L4) and Wilson s disease (B12) can be attributed to kidney malfunction. These are not true examples of underproduction of oxypurines, including uric acid, since the daily output of uric acid is normal. The large number of healthy people who have extremely low serum urate values, however, may indicate that there are individuals who underproduce oxypurines but suffer no ill effects because of this. The one well-documented inborn error that results in underproduction of uric acid is xanthinuria. It has been reported in relatively few cases, probably because individuals with this metabolic abnormality who suffer no ill effects would not come to the attention of a physician. 

Administration of labeled xanthine resulted in the production of a small amount of labeled uric acid, but this could be explained in terms of the action of intestinal bacteria. Several labeled purines were administered to these patients, and the fate of the labeled compounds was consistent with the possible mechanisms of purine metabolism developed through studies of laboratory animals and microorganisms (see Section 2). Thus there was greater utilization of hypoxanthine, xanthine, and guanine than has been seen in individuals who possessed xanthine oxidase (W13), as determined by the delayed release of labeled purines in urine (A7). 

---