THE METABOLISM OF NUCLEIN 445 



its maximum during the early hours of the morning, and subsides 

 to a minimum towards evening. It is apparently unaffected by the 

 periods of digestive and metabolic activity following each meal, 

 but more uric acid is excreted after a rich than after a poor, 

 nitrogenous, purin-free meal. The amount of uric acid is therefore 

 in some way associated with the degree of nitrogenous metabolism 

 of the body. The excess of uric acid may be ascribed in part, at 

 least to the increased functional activity of the body cells. Thus, 

 severe muscular exercise is followed after several hours by a rise in 

 the amount of endogenous uric acid excreted. Also, in diseases where 

 a large amount of cell disintegration is taking place (e.g. , leukaemias, 

 fevers), the output of endogenous uric acid is increased. It is not 

 affected by the giving of diuretics. While endogenous uric acid 

 undoubtedly arises from the destruction of the cell nucleins, the 

 question remains as to whether any can come from other sources. 

 It is known that there is a large hypoxanthin content in muscle, and 

 it may possibly be that some uric acid, especially the increase after 

 muscular exercise, comes from this source. The amount of endogenous 

 uric acid is more than can come from nuclear destruction hi the 

 body. 



It has been demonstrated on birds that perfusion of the liver 

 with ammonia and lactic acid leads to a formation of uric acid. There 

 is no evidence that any such synthesis of uric acid takes place in the 

 mammal. In birds, such a synthesis is homologous to the formation 

 of urea in the liver of a mammal, and therefore it is not to be expected 

 in the latter. It must be concluded that the exact source of all the 

 endogenous purin is not known. The exogenous origin of uric acid 

 is proved by the fact that it is greatly increased in the urine by the 

 giving of foods containing nuclein or purin, especially foods rich in 

 nucleo -protein, such as sweetbreads, and those containing much hypo- 

 xanthin, such as meat extracts. All the purins administered in the 

 food are not, however, excreted in the urine as uric acid; some are 

 excreted as purins. The amount of uric acid formed in the organism 

 varies with the kind of purin fed and the species of the animal which 

 eats it. For example, in man, only one-half of the hypoxanthin 

 administered as such appears as uric acid in the urine, and but one- 

 fourth of the purin in nuclein when that is fed. In the dog, compared 

 with man, about ten times as much purin disappears in its passage 

 through the organism ; in the rabbit, about three times. 



There is doubt as to whether the methyl purins (caffeine, theo- 

 bromine) lead to a formation of uric acid in the organism, or whether 

 they are secreted as purins in the urine. 



One of the symptoms of gout is a permanent increase in the amount 

 of uric acid in the blood a " uricsemia." Various reasons have been 

 ascribed as the cause of this. At one time it was believed to be due 

 to defective excretion of uric acid by the kidney. Research does not 

 lend much support to this view, although it is quite possible that the 

 kidney changes which occur late in the disease may to some extent 

 affect the elimination of uric acid by the organ. 



