682 



METABOLISM 



than in the urine, the excretory factor is partly controlled, and it can 

 be completely so if urine and blood are both investigated. Thanks to 

 the work of Folin, it is now possible to determine with an extreme de- 

 gree of accuracy the uric acid in as little as 10 c.c. of blood. The impor- 

 tance of this achievement will be appreciated when we state that prior 

 to Folin 's work no method existed by which uric acid could be approx- 

 imately measured even when large quantities of blood were available. 

 Much of the work that has been done by the use of this new method 

 has so far applied to the amount of uric acid in the blood of man in 

 various diseases. We shall refer to these results immediately, but 

 meanwhile it is important to call attention to some very suggestive 

 observations concerning the condition of uric acid in the blood. For 

 many years there have been investigators who have thought that uric 

 acid can not be simply dissolved in the blood plasma, like sugar or some 

 inorganic salt. It is believed by many that at least a portion of the uric 

 acid circulates in combination with nucleic (thymic) acid (see page 669), 

 which would account for the fact that some purines are catabolized in 

 the body when they are given in a combined state, as thymic acid, but 

 are excreted unchanged when ingested in a free state. When given freely, 

 certain purines adenine, for example may moreover cause inflamma- 

 tion and calculus formation in the kidneys of dogs, a result not obtained 

 when thymic acid is fed. 



Other observers have concluded that uric acid exists as two isomeric varieties, lac- 

 tam and lactim, the monosodium salts of which are of unequal stability. The 

 less stable a-salt is much more soluble in the blood serum than the stable 

 (3-salt. It is the a-salt that becomes increased in the blood in gout, the deposition 

 of urates in the tissues, which is the most characteristic symptom of this disease, 

 being caused by conversion of the o-salts into /3-salts. The structural formulas of the 

 two isomers are as follows: 



H.N-C : O 



I ! 



O : C C - NH 



I !! 



CO 



H.N - C - NH 



[lactam modification forming 

 unstable a-urates] 

 (relatively soluble) 



N-C.OH 



HO.C C-NH 



I I \ 



C.OH 



I I / 



N = C-N 



[lactim modification forming 

 stable /3-urates] 

 (relatively insoluble) 



The most recent work of S. R. Benedict has shown that uric acid ex- 

 ists, chiefly in combination in the blood of most mammals but not in 

 that of the bird. It was found, for example, that fresh ox-blood exam- 

 ined by the Folin method contains only 0.0005 gm. free uric acid per 100 

 gm. of blood; after boiling the protein-free blood filtrate with hydro- 

 chloric acid, however, the uric acid increased by about ten times. This 



