FORMATION OF URIC ACID 



631 



We now have hypoxanthino and xantliino, wliich, in the presence of 

 oxygen, arc oxidized to form uric acid, thus: 



CsH.N^O + O ► C4H,N«02 



hypoxanthino bypoxanthinc-oxidoso xanthine 



CsH.N.O. + O ►C5H4N4O, 



xanthine xanthine-oxidase uric acid 



Further oxidation of the uric acid causes its conversion into the 

 much more soluble allantoin, thus: 



C5H4N4O3 + O + HoO 



uric acid 



- CJIeX.Oj + CO, 

 allantoin 



It is thus evident that the steps of the disintegration of nucleic acid 

 are numerous, but that each separate process is a simple one; and also, 

 that it has been possible to follow out and distinguish the several steps 

 and to establish the fact that each step depends on a distinct and specific 

 enzyme. Not every tissue possesses all the enzymes of purine destruc- 

 tion, and in different species, of animals the distribution of the enzymes 

 is different. For example, the enzyme xanthine-oxidase, which oxi- 

 dizes xanthine into uric acid, is found in man only in the liver, and also 

 in other animals it is of limited distribution, being found usually only 

 in the liver or in the liver and kidney, but in the dog it seems to be 

 present in several tissues. The deaminizing enzymes, adenase and 

 guanase, are much more widely distributed, but by no means univer- 

 sally. Adenase, for example, is not present in the tissues of the rat, 

 and not in the tissues of adult human beings. ^^ Guanase is absent 

 from the spleen and liver of the pig and from human spleen, although 

 present in most other tissues. Uricase, the enzyme wliich destroys 

 uric acid, also has peculiarities of distribution, being seldom found 

 in any other tissue than the liver or kidney, and being absent entirely 

 from the tissues of man, and from the birds and reptiles so far exam- 

 ined. The significance of this distribution of uricase will be discussed 

 at greater length a little later. 



The following graphic expression of the series of steps leading to 

 the formation of uric acid has been presented by Aniberg and Jones ;^^ 



OH 

 O^P-O.CjHjOj. CjHN.'OH 



0=P-O.CsH,Oj CjH,N,(NHj') 

 OH 



i^ ^-^-^ i^Phospho-n^lcase Pho 



5"°"'"* guonoslne 



C,HN/0*^ .C;H,0, 



odenint 

 C,H,N»CHJHi)C,H,0, C,H,N,(NHO 



/OH 

 C,HN-OH 



acid / Xontlllnt y *: 



- ^ ox\<ia3* AanTh 



C.H,N,<0[] 



lypousnrhintf 

 C,H,N^OH 



'- There have been some reports indicating the presence of adenase in fetal 

 human tissues (Long, Jour. Biol. Chem., 1913 (15), 449). 

 " Zeit. physiol. Chem., 1911 (73), 407. 



