URIC ACID AND THE PURINE BODIES 649 



tion) to the kidneys. These problems have recently been very consider- 

 ably simplified by the elaboration of an accurate method for the estima- 

 tion of the uric-acid content of blood. 



By observing changes in the amount of uric acid in the blood rather 

 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 637), 

 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, lactam and lactim, the monosodium salts of which are of un- 

 equal-stability. The less stable a-salt is much more soluble in blood 

 serum than the stable /?-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 a-salts into /J-salts. The structural formulas of the two isomers 

 are as follows: 



H.N - C : O N - C.OH 



! I II II 



O : C C - NH HO.C C - NH 



j || \0 I ! \.OH 



H.N-C-NH N = C-N 



[lactam modification forming [lactim modification forming 



unstable a-urates] stable j3-urates] 



(relatively soluble) (relatively insoluble) 



