PROTEIN METABOLISM 803 



On giving a large protein meal to a dog, the urea in the urine rapidly 

 rises, and at the end of four or five hours 50 per cent, of the total nitrogen 

 taken in with the food has appeared in the urine as urea (Fig. 364). If we 

 take into account that the digestion of a meat meal in this animal may go 

 on for eight hours, we are justified in the statement that by far the greater 

 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. 



The formation of urea from the ammo-acids is accomplished in a very 

 simple fashion. If amino-acids be treated with the pulp of various organs, 

 there is a production of ammonia, which is not observed when no amino-acids 

 are added to the pulp. Thus leucine, glycine, tyrosine and cystine give 

 rise to ammonia, while none of this substance is produced from phenylalanine. 

 This production of ammonia is due to the presence of deaminising ferments 

 in the cells of the various tissues. According to van Slyke the liver plays 

 the chief part in the break-down of amino-acids, though there is no reason 

 to deny the possession of similar powers to the other tissues, e. g. the muscles 

 of the animal body. As a result of this deaminisation ammonia is set free 

 in the body, and this ammonia is rapidly converted into urea. Whether 

 the ammonia enters the circulation as ammonium carbonate or as ammonium 

 carbamate is uncertain, but in either form it will be quickly changed into 

 urea. This conversion involves a process of dehydration. The ammonium 

 carbonate loses 2 molecules of water and the ammonium carbamate 1 mole- 

 cule, as follows : 



/ONH 4 



CO/ 2H 2 O=CO 



\OHN 4 



X ONH 4 



C0( H 2 = C0< 



X NH 2 



Although there is normally a small amount of ammonia in the urine, it is 

 not increased by injection or administration of ammonium carbonate or 

 carbamate. Either of these two substances administered to man or to an 

 animal gives rise simply to a corresponding increase in the urea of the urine. 

 A large body of evidence points to the liver as being the chief seat of 

 conversion of ammonia salts into urea. Thus Schroder has shown that the 

 liver, even after removal from the body, has the power to transform 

 ammonium carbonate into urea. Defibrinated blood mixed with ammonium 

 carbonate was passed for one hour through a surviving liver. It was then 

 found that the ammonium carbonate had disappeared and that its place 

 was taken by urea, which could be extracted in a crystallised form. 



