Biological precursors of uric acid; the role of lactate, glycine, and carbon dioxide as precursors of the carbon chain and nitrogen atom 7 of uric acid.

Proteins, fats, and carbohydrates or their metabolic derivatives have been investigated in great detail as possible precursors of the carbon chain of uric acid (3-11). The usual procedure has been to test the effect of the administration of these substances on the excretion of uric acid under a variety of experimental conditions. For the most part, experiments have been performed on the fasted animal. The administration of proteins and to a lesser extent of carbohydrates has been shown to increase the excretion of uric acid. Fats, however, either had no effect or caused a decrease in uric acid output. The amino acids, alanine, glycine, asparagine, and glutamine have been shown to cause increased excretion of uric acid in man under conditions in which ammonia or urea did not (12-15). Deaminated derivatives of some of these amino acids have been tested for their effect on uric acid output. Fisher (16) has claimed that L-lactate may increase uric acid excretion in the bird. In an attempt to demonstrate an effect of organic acids in the excretion of uric acid in man, Gibson and Doisy (17) found that lactate and glycolic acid decreased excretion, whereas alanine and pyruvate greatly increased it. Experiments in viva wherein ingested substances were compared for their ability to increase uric acid excretion above the normal level of the fasted subject are open to criticism on the basis of the work of Lennox (18). Lennox has shown that the fasted subject gradually increases his stores of blood and tissue uric acid which may be released by the ingestion of certain foodstuffs, notably carbohydrates and proteins or amino acids. The increased excretion of uric acid, caused by the administration of a substance, may not then represent participation of the administered substance in the synthesis of uric acid but rather a depletion of the body stores. The use of in vitro techniques has likewise brought no definite answer