METABOLISM OF PROTEINS 585 



By oxidation hypoxanthin is changed into xanthin and xanthin 

 into uric acid, and the oxidation seems to be accomplished by a 

 separate oxidizing ferment, xanthin oxidase, whose action may be 

 thus represented : 



C 5 H 4 N 4 + O =C 6 H 5 N 4 2 ; C 5 H 5 N 4 O 2 + O =C 6 H 4 N 4 O 3 . 



Hypoxanthin. Xanthin. Xanthin. Uric Acid. 



Evidence .of the existence of these ferments, and of their wide dis- 

 tribution, has been obtained by making experiments on the various 

 substances mentioned with extracts of different tissues. 



The portion of the uric acid which comes from the food (mainly 

 from the purin bodies in it) is sometimes denominated the exogenous 

 portion, while that which arises from the tissues is called the endog- 

 enous portion. The latter moiety, which generally amounts to 

 about 0-6 gramme in the twenty-four hours, can be estimated by 

 restricting the diet to articles of food free from purin bodies, such as 

 bread, milk, cheese, eggs, and butter. It is stated that the endog- 

 enous uric acid remains practically constant in the same individual 

 under constant conditions, and is unaffected by changes in the diet. 



The total excretion of uric acid (and the other purin bodies) is 

 by no means identical with the sum of the uric acid taken in as 

 purin bases in the food and that produced in the body. A con- 

 siderable destruction of uric acid (and other purin bodies) goes on 

 in the body, and mainly in the liver. The quantity of endogenous 

 uric acid excreted by the kidneys bears a certain ratio to the total 

 amount which has entered the 'circulation. This ratio varies much 

 in different mammalian species. In man a full half is said to be 

 excreted and about a half destroyed, being mainly changed into urea. 

 Some of the exogenous moiety is also broken down. When uric acid 

 is heated in a sealed tube with strong hydrochloric acid, it is broken 

 up into glycin, carbon dioxide, and ammonia. There are grounds 

 for believing that a similar decomposition takes place in the body, 

 and that the products are then transformed to urea in the liver. 



The process of uricolysis, or destruction of uric acid, is usually 

 attributed to a ferment called the uricolytic ferment, and it has been 

 supposed that one of the factors in the production of gout may be 

 a diminution in the amount or activity of this ferment. In some 

 cases it is said to be entirely absent. It is doubtful, however, 

 whether in man and the anthropoid apes the oxidizing enzyme, 

 uricase or uricoxydase, which oxidizes uric acid to allantoin 

 (C 4 H 6 N 4 O 3 ), exists. In all other mammals hitherto investigated it 

 has been found in some of the tissues. In accordance with this, 

 only a trace of allantoin is present in human urine and in the urine 

 of the higher apes, while in the other mammals for example, in 

 the dog a large proportion of the purin excretion assumes this 

 form. It is probable that there is more than one way in which 

 uric acid may be decomposed in the body, and, if so, that there is 



