FORMATION OF URIC ACID 507 



but it is readily formed from any of the purin bases, and the 

 steps by which it is formed are believed to be as follows : 



Nucleoproteids when acted upon by trypsin have the proteid 

 group digested away, leaving the nucleic-acid radical unaffected. 

 Probably in intracellular metabolism the proteolytic enzymes 

 of the cell have a similar action upon the nucleoproteids, set- 

 ting free the nucleic acids, which are then attacked by a specific 

 enzyme (or enzymes) called by Iwanoff " nudease." This 

 enzyme liberates from the nucleic acid the purin bases, of which 

 adenin and guanin are the most abundant. 1 These two sub- 

 stances are in turn acted upon by other specific intracellular 

 enzymes, which, through hydrolysis and liberation of ammonia 

 (deamidization), convert them into xanthin and hypoxanthin, as 

 shown by the following equation : 



C 5 H 5 N 6 + H 2 > C 5 H 4 N 4 2 + NH, 



(guanin) (guanase) (xanthin) 



C 5 H 5 N 6 + H 2 -> C 5 H 4 N 4 + NH 3 



(adenin) (adenase) (hypoxanthin) 



The final step, the conversion of the xanthin and hypoxanthin 

 into uric acid, is accomplished through oxidation by the action 

 of an oxidizing enzyme. First, the hypoxanthin is converted 

 into xanthin : 



C 6 H 4 N 4 + O - > C 5 H 4 N 4 2 



(hypoxanthin) (oxidase) (xanthin) 



and the xanthin is then oxidized into uric acid, thus : 



C 5 H 4 N 4 2 + O - - > C 5 H 4 N 4 3 



(xanthin) (oxidase) (uric acid) 



Not only are these reactions accomplished in the body during 

 metabolism, but it has been found possible to obtain enzyme- 

 containing extracts from the tissues, which will bring about 

 these various reactions when allowed to act upon pure adenin, 

 guanin, etc., outside the body. Each reaction seems to depend 

 upon a specific enzyme. 



Another possible source of uric acid is through synthesis. In 

 birds, which eliminate most of their nitrogen in the form of 

 uric acid, synthesis of uric acid undoubtedly occurs. It would 

 seem possible, therefore, for synthesis of uric acid to occur in 

 mammals, but as yet satisfactory experimental evidence is lack- 

 ing that such synthesis does occur. The greater part, and per- 

 haps all, of the uric acid is formed in mammals through oxida- 

 tion of performed purin groups. 



1 See review by Jones and Austrian, Zeit. pbysiol. Chem., 1906 (48), 110; 

 also full summary by Bloch, Biochemisches Centralblatt, 1906 (5), 521. 



