588 METABOLISM, NUTRITION AND DIETETICS 



amount of urea which can possibly be formed in mammalian metabolism 

 by this process cannot be large, even if most of the arginin, as is the 

 case when it is fed to an animal, is transformed into urea. 



There is no reason to suppose that urea can be directly split off from 

 the other amino-acids with which we are concerned. A comparison 

 of their constitutional formulae with that of urea (or with that of uric 

 acid) shows that a more far-reaching decomposition must take place 

 before products are obtained from which urea (or uric acid) can be 

 formed. Urea has been artificially obtained from protein by oxidation 

 with an ammoniacal solution of permanganate at body-temperature. 

 When the protein is first split into its cleavage products, and these are 

 then oxidized, a very large amount of urea is produced e.g., as much 

 as 3 grammes of urea from 10 grammes of glycin. 



While these facts suggest possible ways of formation of urea in the 

 body, we cannot assume that what happens in the test-tube must 

 happen in the tissues. The best evidence is to the effect that in the 

 body the removal of the amino-group (NH 8 ) in the form of ammonia 

 from the amino-acids is the essential step in the formation of at least 

 a great part of the urea, which is then synthesized from ammonia and 

 carbonic acid . The possibility exists that this deamini zation (or deamidi- 

 zation) of the amino-bodies is the result of hydrolysis, or of oxidation, or 

 of reduction, or of a combination of these processes. Evidence has been 

 found that in the case of some of the amino-acids the deaminization is 

 associated not with hydrolysis in which hydroxyl is substituted for 

 the NH 2 group, but with oxidation (Neubauer) . But this has not been 

 shown to hold good for all amino-acids. In either case, however, 

 whether the deaminization process is oxidative or hydrolytic the nitrogen 

 is split off as ammonia, and it is to such ammonium compounds as have 

 been already mentioned as being transformed into urea when circulated 

 through an excised liver (p. 584) that we have to look for the source of, 

 at any rate, a large portion, of the urea. Ammonia in the form of 

 carbonate or carbamate is constantly found in the blood (p. 585). The 

 excess of ammonia in the portal blood, which, however, is not admitted 

 by all observers to be very large or very constant, has been interpreted 

 as indicating that a considerable decomposition of iamino-acids with 

 liberation of the amino-groups occurs in the intestinal lumen or the 

 intestinal wall. It is not established beyond doubt that ammonia is 

 itself present in the protein molecule, or that its liberation in the 

 hydrolysis of proteins can take place except at the expense of further 

 decomposition of amino-bodies. It has been shown, however, that a 

 great part of the ammonia in the blood is produced in the decomposition 

 of protein in the digestive tube by putrefactive bacteria (Folin and 

 Denis). This is a necessary part of the reaction by which phenol and 

 indol are formed in the intestine. 



It has been generally taught that the deaminization of the surplus of 

 amino-bodies takes place chiefly in the liver, the extra nitrogen being 

 thus ' shunted ' out of the blood-stream before it has had a chance to 

 reach the tissues. It would seem more advantageous in the light of 

 our present knowledge that a large and, so to say, a miscellaneous 

 assortment of amino-bodies should be placed at the disposal of the 

 tissues to facilitate the selection of those which are indispensable. 

 We have seen that tissues such as muscle can and do take up amino- 

 acids when protein is digested in the intestine, and it is very probable 

 that they take up not merely the relatively small amount necessary to 

 replace their wear and tear, but also a portion of the surplus, which 

 after deaminization in the cells takes its place as a source of energy 

 to drive the machine. The nitrogen in the form of ammonia may pass 



