142 METABOLISM 



other hand, contains a relatively large amount, and the evi- 

 dence is very strong that it is the organ in which urea is mainly 

 but not exclusively found. 



1. When an excised liver is perfused with ammonium carbo- 

 nate or other salts of ammonium, these substances may be 

 converted into urea, which is not the case when they are passed 

 through muscle or kidney. 



2. The blood during periods of digestion contains sub- 

 stances which, when perfused through a liver, may be changed 

 to urea. This is not the case when the blood is taken from 

 a fasting animal. Furthermore, the blood of the portal vein 

 during digestion contains several times as much ammonia 

 as does arterial blood. The excess disappears in the liver. 

 It suggests that the intestine furnishes materials which the 

 liver converts into urea. 



3. The establishment of an Eck fistula in dogs, whereby 

 the portal blood is transferred directly into the inferior vena 

 cava, leads to a marked diminution of the quantity of urea 

 excreted, but to an increase of the ammonium salts in the urine. 

 If, at the same time, much protein is fed, characteristic con- 

 vulsions are produced such as appear when ammonium salts 

 are directly injected into the circulation. 



4. In acute yellow atrophy or fatty degeneration of the 

 liver the amino-acids and the ammonia formed in the intestines 

 during digestion pass unchanged through the liver and are 

 excreted by the kidney. Urea almost disappears from the 

 urine, and leucin, tyrosin, etc., and ammonia compounds appear 

 or are increased in quantity. 



That the liver is not the only source of urea is shown by 

 the fact that urea continues to be formed when the liver is 

 removed. Some urea is formed in the tissues generally. The 

 essential process in the manufacture of urea is still a matter 

 of investigation. In the laboratory it may be formed from 

 protein either by hydrolysis or oxidation. Of the hydrolytic 

 products of protein, one is arginin (C 6 H 14 N 4 O 2 ), which by further 

 cleavage forms urea and ornithin. A special ferment, arginase, 

 found in the liver produces this cleavage. Other ferments, 

 de-amidizing ferments, break up ornithin by removing the 

 amide groups leading to its conversion to ammonia and urea. 

 It is important to bear in mind that the hydrolytic cleavage 



