ON UREA AND ON NITROGENOUS METABOLISM. 463 



olism slightly diverging from that leading to urea ; indeed, it is probable 

 that the divergence occurs toward the end of the series of changes, for urea 

 given by the mouth to birds appears in the urine as uric acid, and, con- 

 versely, uric acid given to mammals appears in the urine as area. We 

 have no evidence to prove that the cause of the divergence lies in an insuf- 

 ficient supply of oxygen to the organism at large; on the contrary, uric acid 

 occurs in the rapidly breathing birds as well as in the more torpid reptiles. 

 Nor can the fact that in the frog, again, urea replaces uric acid be explained 

 by reference to that animal having so large a cutaneous in addition to its 

 pulmonary respiration. The final causes of the divergence are to be 

 sought rather in the fact that urea is the form adapted to a fluid, and 

 uric acid to a more solid excrement. Nor is there in man or the mam- 

 mal any satisfactory physiological or clinical evidence that an increase of 

 uric acid is the result of deficient oxidation. The absolute amount of uric 

 acid discharged by man and its proportion to the urea passed at the same 

 time varies a good deal. There is no positive evidence that the quantity 

 excreted is necessarily increased by nitrogenous diet, unless some disorder 

 supervenes ; indeed, it is asserted that both absolutely and relatively to the 

 urea the quantity excreted is greater upon a mixed diet than upon a highly 

 proteid one. Alkalies in the food seem undoubtedly to diminish it, and 

 alcohol, at least in excess, to increase it. 



So far from considering uric acid as a less oxidized antecedent of urea, 

 we ought, perhaps, rather to regard its appearance as a result of a synthesis 

 in which urea or some allied body takes part. As we have said, uric acid 

 may be formed synthetically by heating together urea and glycin ; and it 

 has more recently been similarly prepared from various allied bodies. As 

 to where or how such a synthesis is effected in the living body, we know 

 little or nothing for certain, and can only make conjectures. The constant 

 presence of uric acid in the spleen, however, and the frequently noted con- 

 nection between a rise and fall of uric acid in the urine and variations in 

 the volume and therefore presumably in the activity of the spleen, suggest 

 that the change may be brought about in that organ ; but it must be remem- 

 bered that in birds and reptiles the formation of uric acid seems to be 

 effected in the same organs as that of urea and in an analogous manner ; and 

 the arguments which we have used concerning the formation of urea in the 

 liver of mammals, maybe applied to the formation of uric acid in the livers 

 of birds and reptiles. It is more probable, therefore, that in the mammal 

 the turn to uric acid rather than urea is given in the liver, the spleen, how- 

 ever, possibly playing its part also in the matter. 



405. Of the meaning of the appearance in the tissues of such bodies 

 as xanthin, hypoxanthin, guanin, and the like, and of the exact nature of 

 the metabolism which gives rise to them or which they themselves undergo, 

 we know little or nothing. The presence of these several bodies may be 

 taken as illustrating the complex and varied nature of proteid metabolism 

 to which we referred above. Urea is the chief end-product of proteid 

 metabolism, but that end is probably reached in several ways ; so that prob- 

 ably a very large number of nitrogenous chemical substances make a mo- 

 mentary appearance in the body. Some of these fail to become urea, and 

 either without or after further change make their appearance in the urine. 

 But we do not know whether their appearance is accidental, the result of 

 imperfect chemical machinery, or whether they, though small in quantity, 

 serve some special ends in the economy. Perhaps sometimes or with some 

 of them it is the one case, at other times or with others it is the other case. 



When proteid material undergoes outside the body, either by the action 

 of trypsin or as the result of decomposition or under the influence of chem- 



