412 METABOLISM, NUTRITION, AND DIET 



urea in the blood leaving an isolated living liver through which an artificial 

 circulation is kept up. When ammonium carbamate and other ammonium 

 salts are added to the blood, the urea increases more rapidly and to a greater 

 extent. This change occurs even when the living hepatic tissue is chopped 

 up and simply mixed with the ammonium compounds in a beaker. 



If blood from a well-fed animal be circulated through the isolated liver, 

 there is a distinct increase in the amount of urea it contains. On the other 

 hand, if the blood be from a fasting animal there is little or no increase of 

 urea. Evidently, then, the blood from a well-fed animal contains something 

 which the liver cells are capable of transforming into urea. And, finally, if 

 the liver be removed and the animal kept alive, as has been done by Pawlow, 

 there is a marked diminution in the quantity of urea in the urine. The 

 power of the liver to form urea is thus demonstrated. The question which 

 now presents itself is, what is this antecedent substance or substances ? 



It has already been indicated that urea follows closely the amount of 

 proteid taken with the food, hence we must look directly to the nitrogenous 

 fraction of proteid cleavage as the final source of urea. While the different 

 steps in the process of cleavage, probably hydrolytic (Folin), are yet very 

 obscure, still it is believed that proteids are first broken down to an ammonia 

 stage and then again built up into urea by the liver. It is now believed that 

 ammonium carbamate is at least one true antecedent of urea. 



In these experiments the liver is first shut out of the general circulation 

 by an Eck's fistula connecting the portal vein with the vena cava. This 

 operation cuts off the chief blood supply of the liver, viz., the portal blood, 

 but it leaves the small hepatic artery with its oxygen supply to the liver. 

 When animals survive this operation it is found that they can live only when 

 fed very carefully on a mixed diet from which proteids are almost entirely 

 eliminated, and that, if the food contain an excess of proteids, convulsions 

 ensue with fatal termination. Investigation of the composition of the urine 

 and of the blood, with the Eck's fistula, shows that the end product of proteid 

 metabolism is represented by ammonium carbamate and that there is a con- 

 siderable decrease in urea. If ammonium carbamate is injected into the 

 blood of normal animals in a larger quantity than the liver can dispose of, 

 death ensues, following convulsions of the same nature as those produced 

 by an excess of proteid food in the animals operated on. Ammonium car- 

 bamate is shown to be, in part at least, the direct antecedent of urea; it is also 

 shown to be a toxic substance which may cause death by accumulating in 

 excess. The reaction by which the liver changes it to the inert form of urea 

 is as follows: 



NH 2 NH 2 



/ / 



CO H 2 = CO 



\ \ 



OHH 4 NH 2 



Ammonium carbamate. Urea 



