The Effect of Glycine on the Production and Excretion of Uric Acid.

Although most investigators ( 1 to 4) have agreed that the ingestion of protein increases the output of uric acid in man, there has been no clear elucidation of the mechanism whereby this is accomplished. Mares (5) believed that the increased uric acid in urine following high protein feeding resulted from the deterioration of nuclei of digestive cells concerned in the assimilation of the ingested protein. He offered in support of this theory the observation that atropine decreased and pilocarpine increased the output of uric acid. Taylor and Rose (1) found that, although urinary uric acid increased after an intake of high protein, the excretion of urinary creatinine did not change. Lewis, Dunn and Doisy (4) administered various amino acids to men in order to obviate as much as possible the probability of digestive gland activity necessarily involved in converting protein into its constituent amino acids. They found that all amino acids tested except sarcosine increased the output of uric acid. Since this latter amino acid was not catabolized in the body, the authors concluded that the uric acid metabolism of the body was increased by the specific dynamic action of catabolizing amino acids. Rose (6) concluded that the increase in uric acid output after high protein ingestion was due to generalized cellular stimulation occasioned by a higher caloric intake, thus implying that the increase in urinary uric acid was due to some intrinsic protein or amino acid effect. Christman and Mosier (7) gave glycine to subjects and observed an increased urinary uric acid but no change in the renal excretion of creatinine. They apparently concurred with Rose's theory concerning the general stimulating effect of protein or amino acids on cellular metabolism with consequently increased production and secondarily increased excretion of uric acid. Quick lAided by a grant from the Dazian Foundation for Medical Research. (8) also observed that glycine feeding increased uric acid excretion, particularly when combined with salicylate ingestion. However, various observations have been made which cannot be fitted in with the theory of increased production of uric acid after ingestion of protein or amino acids. Thus, although Lewis, Dunn, and Doisy (4) implied that the specific dynamic action of ingested amino acids effected an increased production of uric acid, they also found that glutamic acid (an amino acid without significant dynamic action) increased uric acid output as markedly as any amino acid tested. Furthermore these investigators in this particular study never determined the concentration of uric acid in blood after ingestion of amino acids-it was assumed apparently that such a rise occurred because of the increased urinary output observed. Later however, Gibson and Doisy (9) were unable to detect a rise in blood uric acid in man after the ingestion of amino acids. Finally, Pitts (10) showed that an excess of an amino acid (glycine) might influence the renal excretion of a blood constituent not by increasing the production of the latter but by competing with it in the renal tubular reabsorptive process. These latter observations suggested the possibility that excess amino acid ingestion might increase urinary uric acid not by initially increasing the concentration of the latter in the blood but by interfering with its renal tubular reabsorption after its glomerular filtration (11). In order to explore the validity of this last possibility as well as to determine other possible mechanisms involved in the increased excretion of uric acid after ingestion of amino acids, rats were given glycine. Studies then were made of the creatinine, hippurate and uric acid clearances together with the blood uric acid concentrations. Similar studies with the exception of the hippurate clearance were made on 2 human subjects.