URIC ACID AND THE PURINE BODIES 673 



of the pig, in the urine of which animal it has also been found that the 

 purine bases are in excess of the uric acid. This absence of guanase 

 no doubt accounts for the fact that deposits of guanine may occur in the 

 muscles, and that these may be so large as to constitute the condition 

 known as guanine gout found in this animal. Adenase, on the other 

 hand, is absent from the organs of the rat, which again corresponds with 

 the fact that, when adenine is injected subcutaneously into these ani- 

 mals, it undergoes oxidation without the removal of its amino group. 

 In the human organism, adenase appears to be absent from all of the 

 organs, whereas guanase is present in the kidney, lung and liver, but 

 not in the pancreas or spleen. Xanthine-oxidase exists only iri the liver. 



The distribution of uricase is perhaps the most interesting. It is pres- 

 ent in most of the lower animals. On account of its presence extracts 

 of the liver, spleen, etc., in all breeds of dogs, with the exception of 

 Dalmatians, rapidly destroy uric acid; and practically no uric acid 

 when injected subcutaneously can be recovered unchanged in the urine, 

 but appears as allantoine. Uricase, however, is absent in man. This has 

 been demonstrated by finding (1) that when uric acid is injected sub- 

 cutaneously, nearly all of it reappears in the urine, and (2) that uric acid 

 is not destroyed when extracts of the organs are incubated with uric 

 acid or its precursors at body temperature. It must of course be kept 

 in mind that, although the uric acid is thus shown not to be destroyed 

 in vitro, it may nevertheless be destroyed in the living animal. 



The importance of the above described results rests in the fact that 

 from them we may hope to be able, ultimately, to state exactly in what 

 organs and tissues the intermediary metabolic processes concerned in 

 nucleic acid metabolism occur. The work at the present time is of spe- 

 cial significance, since it represents one type of evidence which we must 

 have before we can trace exactly every step in the metabolism of any 

 other biochemical substance. 



The absence of uricase from the tissues of man places him in a unique 

 position with regard to the metabolism of nucleic acid, and renders the 

 investigation of the problem particularly difficult, since investigations 

 on the usual laboratory animals are useless. Recently, however, S. R. 

 Benedict has, discovered that the Dalmatian breed of dog also known 

 as the carriage dog, and having a spotted or mottled skin has a purine 

 metabolism like that of man. 4 When fed on food containing no purine 

 substances, a dog of this breed excretes large quantities of uric acid, and 

 when the latter substance is injected subcutaneously, it is eliminated 

 quantitatively as such in the urine. We shall see later how experiments 

 on this animal have been made use of in the investigations of problems 

 of purine metabolism as applied to man. In all other animals most of the 



