THE FORMATION OF UREA 661 



the tissues into simpler compounds, which are ultimately con- 

 verted into and leave the body chiefly as urea. At the same time 

 it has been supposed that an unknown proportion of the total 

 urea- nitrogen may have had a different history, and that it is 

 derived from the breaking down of proteids not in the tissue 

 but in the alimentary canal. Folin has recently put forward a 

 wholly different view of proteid metabolism, and divides the 

 nitrogenous katabolism into endogenous and exogenous. The 

 endogenous or tissue metabolism is represented in the urine by 

 kreatinin, uric acid, neutral sulphur, and possibly a very small 

 proportion of the total urea. The bulk of the urea and the 

 inorganic sulphate represent the exogenous katabolism, that is, 

 the proteid which is broken down during digestion and absorption 

 and never built up again into proteid or bioplasm. According 

 to this view urea is not the chief end product of nitrogenous 

 tissue metabolism, as in views of Voit and Pfliiger, but is the 

 form in which the nitrogen of the food which is in excess of the 

 tissue needs is passed out of the body after having been broken 

 down in the alimentary canal. According to all of the three 

 views urea possibly has a double origin, the tissues, and the 

 alimentary canal apart from the tissues. 



It is impossible to follow in detail the breaking down of 

 proteid in the alimentary canal of a living animal, and our 

 knowledge is derived chiefly from the action outside the body 

 of digestive ferments and other hydrolytic agents. It is even 

 more difficult to follow in the living animal the steps in the 

 disintegration of tissue proteid which might lead to the formation 

 of urea. The views which have been held as to what substances 

 are the immediate precursors of urea, and by what process urea 

 is formed from them, have been founded both on chemical 

 and experimental evidence. Proteids have been oxidised by 

 various agents and hydrolysed by digestive ferments, acids, or 

 alkalies ; many of the simpler nitrogenous products so obtained 

 have been chemically converted into urea ; the same products 

 have been placed in the alimentary canal, or injected into animals, 

 or circulated through their organs, and the formation of urea 

 investigated. The subject has been rendered more difficult partly 

 because of our ignorance of the actual constitution and mode of 

 cleavage of the complex proteid molecule, and partly because 

 both the end and intermediate products formed by the action of 



