PROTEIN METABOLISM 759 



portion of the protein nitrogen taken with the food is excreted almost 

 directly after absorption as urea in the urine. Urea is therefore to be re- 

 garded in the first place as an index to the amount of protein absorbed. We 

 have seen that the end-products of protein digestion in the intestine are 

 the amino-acids ; and that these are the immediate precursors of the urea 

 is shown by the fact that the administration of these bodies is followed very 

 rapidly by the appearance of the whole of their nitrogen in the urine as 

 urea. Many attempts have been made to explain the method by which urea 

 may be derived from the amino-acids. 



F. Hofmeister succeeded in preparing urea by oxidising amino-acids 

 with potassium permanganate in the presence of ammonia and ammonium 

 sulphate. He assumes that urea is formed by an oxidation synthesis. 

 The first step would be the formation, by oxidation of protein or amino-acids, 

 of the group CONH 2 , and this at the moment of formation would combine 

 with the NH 2 left over in the oxidation of the ammonia to form urea, 



According to Drechsel and Nencki, the immediate precursor of the urea 

 is probably ammonium carbamate, which loses a molecule of water, thus : 



w n nr >^ 2 

 NH 2 H2 ! <NH 2 



Schroder, on the other hand, suggested that the urea was formed from 

 ammonium carbonate by the loss of two molecules of water. 



In all these views it is assumed that before urea can make its appearance 

 in the urine there must be a complete destruction of the amino-acid. If 

 we compare the structure of any amino-acid with that of urea we see that the 

 proportion of carbon to nitrogen is very much greater in the former than in 

 the latter, and that even after splitting off from two molecules of amino-acid 

 the necessary elements to form urea, CON 2 H 4 , almost the whole of the 

 molecule will be left in an unoxidised condition. A complete oxidation 

 of the amino-acid would result in the production of ammonia, carbon dioxide, 

 and water, so that if oxidation were the method adopted for the production of 

 urea the immediate precursor of this substance would be a combination 

 of ammonia and carbonic acid, either ammonium carbonate as suggested 

 by Schroder, or carbamate as thought by Dreschel. We have distinct evi- 

 dence that ammonia in one of these two forms is an important precursor of 

 urea. If ammonium carbonate or carbamate be administered to man or 

 to an animal the whole of it is turned out in the urine as urea. Although 

 there is normally a small amount of ammonia in the urine, it is not in- 

 creased by injections of ammonium carbonate. Schroder has shown that 

 the liver, even after removal from the body, has the power of transforming 

 ammonium carbonate into urea. Defibrinated blood mixed with ammonium 

 carbonate was passed through a surviving liver. After a little time it was 



