THE FORMATION OF UREA 439 



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 transporting 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 

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

 fraction of protein 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 ammonia is split off from the protein cleav- 

 age products and is then 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 proteins 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 pro- 

 tein metabolism is represented by ammonium carbonate carbamate and 

 that there is a considerable decrease in urea. If ammonium salts are in- 

 jected 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 protein food in the animals operated on. 



Ammonium carbamate is shown to be, in part at least, the direct ante- 

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

 form of urea is as follows: 



ONH 4 NH 2 NH 2 



/ / / 



CO H 2 O . CO H 2 O > CO 



\ \ \ 



ONH 4 ONH 4 NH 2 



Ammonium carbonate. Ammonium carbamate. Urea. 



The elimination of urea is increased very slightly by muscular activity. 

 But there is no direct relationship between the amount of work done and the 

 amount of nitrogen excreted as urea. 



There is experimental evidence to show that while the liver produces the 



