678 METABOLISM 



In the early days of research in the uric-acid problem, not inconsid- 

 erable mistakes were made on account of failure to recognize the essen- 

 tial difference in the metabolism of uric acid in birds and mammals, 

 and the tendency for some time after the exact state of affairs was 

 discovered was to consider that in mammals none of this synthetic proc- 

 ess occurs. The latter view, however, is surely incorrect, for a cer- 

 tain amount not only of uric acid itself but of the lower purine bodies 

 can be produced by synthesis in the mammalian body. Thus, Ascoli and 

 Izar 47 discovered that uric acid could be made either to disappear or 

 to be formed when a minced preparation of liver was incubated, the ex- 

 act result depending upon whether the incubation was conducted in the 

 presence of oxygen or of carbon dioxide. With oxygen uric acid disap- 

 peared, whereas with carbon dioxide uric acid accumulated, indicating 

 that in the presence of this gas the destroyed uric acid became reformed 

 from the disintegration products of the oxygenation process. As similar 

 results were obtained from the livers of birds, it is clear that no essential 

 difference exists between the purine metabolic processes occurring in 

 the livers of birds and of mammals. The difference is a quantitative not 

 a qualitative one. 



Eegarding the chemical nature of the product into which uric acid is 

 broken down and from which it may be resynthetized, it has been pos- 

 sible so far to identify but one substance namely, dialuric acid. This 

 is a perplexing result, for from all other investigations it would appear 

 that in mammals, with the exception of man and the anthropoid apes, 

 uricase splits uric acid into allantoine (see page 673), which substance, 

 however, when added to liver extract does not cause any uric acid to be 

 formed; nor do any of the other known decomposition products of uric 

 acid have such a result. The chemical reaction involved in the produc- 

 tion of uric acid from dialuric acid and urea is indicated as follows: 



NH C = 



/ \ 





O = C C I H.OH H ! NH 



\ 4 = 



NH c; = o H i NH 



(dialuric acid ) ( urea ) 



The synthesis of uric acid is brought about by the combined action 

 of a thermolabile enzyme in the blood and a thermostable body in the 

 tissues. An aqueous extract of blood-free liver of the dog can destroy 

 uric acid only in the presence of oxygen; it can not reform it even in 



