544 WASTE^PRODUCTS 



and since the discovery by Kossel and Dakin of the existence of an 

 enzyme, Arginase in aqueous extracts of the liver, spleen, thymus and 

 intestinal mucosa which directly splits arginine with the production of 

 urea, and Ornithine : 



/NH 2 



HN = C< + H 2 



X NH.CH 2 .CH 2 .CH 2 .CH(NH 2 ) .COOH 

 Arginine. 



-/NHj 



CO + CH 2 .(NH 2 )CH2.CH2.CH(NH 2 ).COOH 



Urea. Ornithine. 



there can be no doubt that a proportion of the urea output originates 

 in this manner. It can only be a small proportion, however, since 

 urea forms over eighty per cent, of the total nitrogen output and only 

 a very small percentage of the nitrogen intake is in the form of arginine 

 radicals. 



The origin of the greater part of the urea output is undoubtedly to 

 be traced to Ammonia formed by deaminization from the various amino- 

 acids. We have seen that the decrease of urea output which accom- 

 panies interference with the liver-functions also results in a correspond- 

 ing increase of the ammonia output in the urine, and this fact in itself 

 would point to ammonia as a precursor of urea. It can, however, be 

 directly shown that when ammonia in the form of Ammonium Carbonate 

 is supplied to the liver, it is transformed therein into urea. Thus 

 Nencki and Pawlow have shown that the percentage of ammonia con- 

 tained in the blood from the portal vein is considerably higher than it 

 is in the blood from the hepatic vein, showing that the ammonia is 

 retained by the liver as the portal blood passes through it. Further- 

 more, when ammonium carbonate is administered to animals it appears 

 in the urine as urea, and, finally, von Schroeder perfused the isolated 

 liver of the dog with ammonium carbonate and obtained, not only the 

 retention of ammonia observed by Nencki and Pawlow, but also an 

 actual replacement of the perfused ammonium carbonate in part by 

 urea. Ammonium Formate was similarly transformed. The conversion 

 of ammonium salts into urea by the tissues of the liver has therefore 

 been confirmed in a variety of ways. 



Urea is the diamide of carbonic acid and may be derived from 

 carbonic acid by the successive introduction of amino-groups, an inter- 

 mediate stage of the process being the formation of Carbamic Acid: 



/O.NH 4 /NH 2 



c=o - c=o > c=o 



\).NH 4 \NH 2 



H 2 O H 2 O 



Ammonium carbonate. Ammonium carbamate. Urea. 



