CH. XXXVII.] FORMATION OF UREA 557 



in support of the theory that urea is formed in the liver. The 

 principal are the following : 



1. After removal of the liver in such animals as frogs, urea 

 formation almost ceases, and ammonia is found in the urine instead. 



2. In mammals, the extirpation of the liver is such a severe 

 operation that the animals do not live. But the liver of mammals 

 can be very largely thrown out of gear by connecting the portal vein 

 directly to the inferior vena caVa (Eck's fistula). This experiment 

 has been done successfully in dogs ; the amount of urea in the urine 

 is lessened, and its place is taken by ammonia. 



3. When degenerative changes occur in the liver, as in cirrhosis 

 of that organ, the urea formed is much lessened, and its place is 

 taken by ammonia. In acute yellow atrophy urea is almost absent in 

 the urine, and, again, there is considerable increase in the ammonia. 

 In this disease leucine and tyrosine are also found in the urine; 

 undue stress should not be laid upon this latter fact, for the leucine 

 and tyrosine doubtless originate in the intestine, and, escaping 

 further decomposition in the degenerated liver, pass as such into 

 the urine. 



We have to consider next the intermediate stages between proteid 

 and urea. A few years ago Drechsel succeeded in artificially pro- 

 ducing urea from casein. More recent work has shown that this is 

 true for other proteids also. If a proteid is decomposed by hydro- 

 chloric acid, a little stannous chloride being added to prevent 

 oxidation, a number of products are obtained, such as ammonium 

 salts, leucine, tyrosine, aspartic, and glutaminic acids. This was 

 known before, so the chief interest centres round two new sub- 

 stances, precipitable by phosphotungstic acid. One of these is 

 called lysine (C G H U N 2 2 , di-amino-caproic acid) ; the other was first 

 called lysatinine. Hedin then showed that lysatinine is a mixture 

 of lysine with another base called arginine (OgH^^O.,) ; it is from 

 the arginine that the urea comes in the experiment to be next 

 described. Arguing from some resemblances between this substance 

 and creatine, Drechsel expected to be able to obtain urea from it, 

 and his expectation was confirmed by experiment. He took a silver 

 compound of the base, boiled it with barium carbonate, and after 

 twenty-five minutes' boiling obtained urea. (See note on p. 573.) 



It is, however, extremely doubtful whether the chemical decom- 

 positions produced in laboratory experiments on proteids are com- 

 parable to those occurring in the body. Many physiologists consider 

 that the amino-acids are intermediate stages in the metabolic 

 processes that lead to the formation of urea from proteids. We have 

 already alluded to this question in relation to the creatine of muscle, 

 and we are confronted with the difficulty that injection of creatine 

 into the blood leads to an increase not of urea, but of creatinino 



