646 METABOLISM 



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

 the presence of carbon dioxide. On the other hand, blood serum can 

 not reform uric acid, whereas a mixture of the bloodless liver extract 

 and blood serum produces uric acid readily under suitable conditions. 

 Boiling of the liver extract does not affect the result, but boiling of the 

 blood serum renders it incapable of exerting its joint action with the 

 bloodless liver extract. 



These experiments with dog's liver serve only as circumstantial evi- 

 dence that uric-acid synthesis occurs in mammals as well as in birds. 

 More direct proof that purine synthesis occurs in mammals is as follows: 

 (1) It was discovered long ago by Miescher that salmon, after leaving 

 the sea to ascend the rivers, have a well-developed muscular system, but 

 that in the upper reaches of the stream the muscular system becomes 

 considerably atrophied and the testes enormously developed. As the 

 fish takes no food during the migration, there must be conversion of 

 the protein of the muscles into the cellular tissue of the sexual glands, 

 and nucleic acid must be produced. (2) A hen's egg before its incuba- 

 tion contains practically no nucleic acid, whereas after development has 

 well started nucleic acid increases by leaps and bounds. Similarly the 

 eggs of insects increase in purine content very markedly as development 

 proceeds. (3) Milk contains practically no purine derivative, and yet 

 when it is fed to young growing animals, the organs lay on purine sub- 

 stances abundantly. In general, indeed, it may be said that the combined 

 purine increase is in proportion to the increase in body weight on the 

 milk diet. (4) In Osborne and Mendel's experiments already alluded 

 to, it has been shown that adequate growth depends primarily on the 

 nature of the protein building stones, and not upon the purine content 

 of the food. (5) An objection might be raised to these results on the 

 score that they do not apply to the adult mammal. Investigation of 

 the problem has hitherto been seriously impeded by the fact that 'no or- 

 dinary laboratory animals were known in which uric acid is excreted in 

 the urine. The discovery that this occurs in the Dalmatian dog has, 

 however, made it possible for S. R. Benedict* 1 to show, not only that 

 after increasing the amount of nonpurine food there was a very distinct 

 increase in the uric-acid excretion, but also that when the animal was 

 kept for a year on such foods there was excreted a total amount of uric . 

 acid at least ten times greater than could have come from the traces 

 unavoidably included in the food. 



Regarding the chemical nature of the substance from which the purine 

 is synthesized, we know at present practically nothing. No doubt some 

 of the protein building stones functionate in this capacity, pyrimidine 

 being probably the product that is first formed. Thus, pyrimidine may 



