632 URIC-ACID METABOLISM AND GOUT 



Another possible source of uric acid is through synthesis. In 

 birds, which ehminate most of their nitrogen in the form of uric acid, 

 synthesis of uric acid undoubtedly occurs. It must also be considered 

 that young mammals can synthesize the purines necessary for their 

 growth from foods which contain no purines. ^^ It would seem possi- 

 ble, therefore, for synthesis of uric acid to occur in adult mammals, 

 but as yet satisfactory experimental evidence is lacking that such 

 synthesis does occur, although an apparently reversed reaction, 

 whereby uric acid destroyed by liver tissue can be resynthesized by 

 the same tissue acting upon it in the absence of oxygen, has been de- 

 scribed by Ascoli and Izar.^^ Their work has not been repeated suc- 

 cessfully by others. I have failed in several attempts to secure re- 

 synthesis of uric acid by dog livers, and Spiers,^'' who made a more 

 extensive investigation, was unable to corroborate their findings. 



It should also be mentioned that not all of the purine bases of the 

 body is bound in the form of nucleic acid. A considerable amount is 

 present in a free condition, or at least not bound in nucleic acid, espe- 

 cially in muscle tissue. Uric acid can be formed as well from the free 

 purine bases as from purine bases liberated from nucleic acid — indeed, 

 evidence has been brought forward indicating that a large proportion 

 of the uric acid arising during metabolism (endogenous) comes from 

 the free hypoxanthine of the muscles. 



As to the place where uric acid is formed, it seems probable that in 

 different animals different organs are chiefly concerned, for it has 

 been found that the distribution of the enzymes mentioned above 

 varies greatly in the various orgaps and tissues of dijfferent species. ^^ 

 In most animals the xanthine oxidase, which forms uric acid from xan- 

 thine, is localized chiefly or solely in the liver, and this is the case in 

 man; therefore it is presumable that uric acid is formed chiefly in the 

 liver from purines by the steps described above. That there may be 

 other methods of forming uric acid is possible. 



DESTRUCTION OF URIC ACIDi* 



With most mammals but little of the total amount of purine bases 

 taken as food or set free in the tissues, appears in the urine as uric 

 acid, most of it being converted into allantoin, which seems to be ex- 

 creted with little or no loss.^'-* Thus, when dogs, pigs or rabbits are 

 fed nucleic acid, about 93 to 95 per cent, can be recovered as allantoin, 

 3 to 6 per cent, as uric acid, and 1 to 2 per cent, as i)urine bases (Schit- 

 tenhelm). It would seem that practically all the purines can be found 



" McCollum, Amer. Jour. Physiol., 1909 (25), 120. 



"See Zeit. physiol. Chem., 1910 (65), 78. 



'SBiochem. .lour., 1915 (9). 837. 



1' A compilation of this distribution is given by Wells, Jour. Biol. Chein., 1910 

 (7), 171. 



'* See discussion by Wells, Jour. Lab. Clin. Med., 1915 (1), 104. 



" Allantoin may be found in the blood of other nuimmals but not in man 

 (Hunter, Jour. Biol. Chem., 1917 (28), 369). 



