426 R. M. S. SMELLIE 



Still lower forms of animal life degrade the urea to ammonia and carbon 

 dioxide by means of the enzyme urease, thus reducing the nucleic acid 

 purine to the simplest of units. A large number of enzymes is concerned 

 in this process of degradation and their distribution has been summarized 

 by Florkin/^^ Baldwin,"^ and Laskowski/" and also in Chapter 15 of this 

 volume. 



In birds and reptiles, the chief end-product of all nitrogen metabolism 

 is uric acid. This probably represents an attempt to spare the water which 

 would be required in the excretion of other more soluble nitrogenous end- 

 products. The synthesis of uric acid and tissue purines in pigeons has been 

 studied by Barnes and Schoenheimer^''* using ammonium citrate labeled 

 with N^^. They found considerable incorporation of the isotope into the 

 tissue purines as well as into the excreted uric acid, and conclude from 

 their calculations that the synthesis of uric acid from ammonia in the 

 pigeon (the major pathway for the excretion of nitrogen) passes through 

 the purines of at least some of the tissue nucleic acids. The catabolism of 

 purines by several microorganisms has been reviewed by Brown.^^ 



h. The Metabolism of Uric Acid 



The metabolism of uric acid has recently been reviewed by Bishop and 

 Talbott.^'^^ In man and in certain higher primates in contrast to most other 

 mammals, uric acid appears to be the main end-product of purine metabo- 

 lism; only small quantities of allantoin, possibly of dietary origin, appear 

 in the urine. This anomaly in purine metabolism is due to the absence of 

 uricase from the tissues of these species. Geren et al}^° have studied the 

 fate of N^^-labeled uric acid administered orally and intravenously to 

 normal men and have found that orally administered uric acid is largely 

 degraded to urea, whereas the bulk of the intravenous uric acid is excreted 

 unchanged. Other workers'^^ have found that, after intravenous injection 

 of N^^-labeled uric acid, only 68 to 77% of the administered isotope was 

 recovered in the uric acid of the urine. Alternative metabolic pathways 

 would therefore appear to exist. Recently, Wyngaarden and Stetten^^^ 

 have carried out similar studies from which they conclude that about 18 % 

 of the administered uric acid is degraded to urea and ammonia and some 6 % 

 appears in the feces. Repetition of this experiment in a subject in whom 



"' M. Laskowski, in "The Enzymes," (Sumner and Myrback, eds.), Vol. 1, Part 2, 



p. 946. Academic Press, New York, 1951. 

 178 F. W. Barnes, Jr., and R. Schoenheimer, /. Biol. Chem. 151, 123 (1943). 

 "9 C. Bishop and J. H. Talbott, Pharmacol. Revs. 5, 231 (1953). 

 18" W. D. Geren, A. Bendich, 0. Bodansky, and G. B. Brown, J. Biol. Chem. 183, 



21 (1950). 

 '" J. Buzard, C. Bishop, and J. H. Talbott, /. Biol. Chem. 196, 179 (1952). 

 182 J. B. Wyngaarden and DeW. Stetten, Jr., J. Biol. Chem. 203, 9 (1953). 



