DESTRUCTION OF URIC ACID 033 



in these three forms combined, the proportions varying in (hfTerent 

 species. In man alone, except for the chimpanzee-'" and oraiiK-utan, 

 does a considerable proportion escape as uric acid, a fact in complete 

 harmony with repeated observation that the tissues of man hav(! no 

 power whatever to destroy uric acid in vitro; the earlier reports of 

 positive uricolysis undoubtedly being erroneous. Even the monkey 

 has active uricolytic enzymes in its hver, and therefore e.xcrotos its 

 purines chiefly as allantoin. With mammals as a whole, therefore, 

 uric acid is destroyed to the extent of being converted into allantoin,-' 

 the close relationship of which to uric acid is shown by the structural 

 formula : 



NH -CH-NH 



0=C C=0 



NH2 CO -NH 



(allantoin) 



With most mammals the oxidation of uric acid takes place chiefly in 

 the liver, but in some of the herbivora the kidneys are more active, as 

 far as experiments in vitro can show. 



Whether man can defetroy uric acid at all has been a matter of dis- 

 pute. It has been shown by Wiechowski and others that uric acid 

 injected subcutaneously is excreted almost quantitatively and un- 

 changed in the urine. To be sure, human urine does contain a very 

 little allantoin, 7 to 14 mg. per day, but this amount is too small to be 

 of much significance, for it is possibly all derived from the food, as 

 the human organism cannot destroy allantoin. 2- On the other hand, 

 it has been found repeatedly that nucleic acid or purines given by 

 mouth are by no means quantitatively excreted in the urine, even 

 when uric acid, allantoin and purine bases are added together. Ap- 

 parently a considerable proportion of the purine nitrogen fed, about 

 half in most experiments, is excreted as urea.-^ As allantoin seems 

 not to be at all disintegrated in the human body it would seem prob- 

 able that if purines are destroyed, as these experiments indicate, they 

 pass through some other route than allantoin, and possibly that part 

 of the purines which is destroyed does not pass through the stage of 

 uric acid. Experiments show that outside the body uric acid can be 

 destroj^ed by other routes than through allantoin; thus, it can be dis- 

 integrated into glycine, ammonia and CO2; or by another method of 

 destruction it yields first alloxan (C4H0N2O4), then parabanic acid 

 (C3H2N2O3) which in turn yields oxalic acid and urea. There is no 



20 Wiechowski, Prager med. Woch., 1912 (37), 275; Wells and Caldwell, Jour. 

 Biol. Chem., 1914 (18), 157. 



21 See Hunter and Givens, Jour. Biol. Chem.. 1914 (18), 403. 



22 See Ackroyd, Biochem. Jour., 1911 (5), 217, 400, 442. 



" See Taylor, Jour. Biol. Chem., 1913 (14), 419; Givens and Hunter, ibid., 1915 

 (23), 299. About one-tenth as much uric acid is excreted in the sweat as in the 

 urine, sweat containing 0.1 mg. per c.c. (Adler, Deut. Arch. kUn. Med., 1916 

 (119), 548). 



