CH. XXXIX.] URIC ACID 593 



conclusion is therefore drawn that in these animals, ammonia and 

 lactic acid are normally synthesised in the liver to form uric acid. 



But in mammals, this is not the history of uric acid formation ; 

 in these animals, including man, uric acid is the end-product of the 

 metabolism of nuclein, from the bases of which it arises by oxidation. 



Nuclein, the main constituent of the nuclei of cells (see p. 431), 

 yields, on decomposition, certain products called purine substances, 

 and their close relationship to uric acid is shown by their formulae : 



Purine 



Hypoxanthine (inonoxypurine) 



Purine bases,' Xanthine (dioxypurine) 

 ^ Adenme (ammo-purme) 



I 



Guanine (amino-oxypurine) 

 Uric acid (trioxypurine) 



C 5 H 4 N 4 



C 5 H 4 N 4 



C 5 H 4 N 4 0., 



C 5 H 3 N 4 .NHo 



C 5 H 3 N 4 O.NH 2 



C 5 H 4 N 4 3 



Just as the ordinary protein metabolism is both exogenous and 

 endogenous, so is it the case with nuclein metabolism. There are 

 certain kinds of food (such as liver and sweetbread) which are rich 

 in nuclei, and others, such as meat, which are rich in purine bases 

 (especially hypoxanthine). The increase in uric acid excretion after 

 partaking of such food is exogenous, and those liable to uric acid 

 disorders should avoid such articles of diet. Other forms of diet 

 lead to an increase in uric acid formation by increasing the number 

 of leucocytes in the blood, and there is a consequent increase in the 

 metabolism of their nuclei. Increase in leucocytes may, however, be 

 present independently of diet, and in the disease known as leucocy- 

 thcemia, this occurs to a marked degree; in such cases ^uric acid 

 formation increases. Although special attention has been directed 

 to the nuclei of leucocytes because these can readily be examined 

 during life, it must be remembered that the nuclein metabolism of 

 all cells may contribute to uric acid formation. Uric acid, which 

 originates by metabolism, is spoken of as endogenous. 



We must next consider the mechanism by which the tissue cells 

 form uric acid from nuclein. ,This question is not only of interest 

 in itself, but also because it illustrates a general truth concerning 

 the importance of the tissue enzymes. The enzyme of the liver 

 which turns glycogen into sugar is the oldest known example of 

 these; in more recent times, the importance of autolytic enzymes 

 (see pp. 136 and 440) of tissue erepsins (see p. 546) and arginase 

 (see p. 587) has been recognised. In uric acid formation we have 

 the very striking example of the action of a succession of enzymes. 

 These are present to an almost negligible extent in the juices of the 

 alimentary canal, and have been studied in the extracts of different 

 organs ; their distribution varies a good deal in different animals, 

 and in the different organs of the same animal ; speaking generally, 

 they are most abundant in liver and spleen. The general term 



2 ? 



