578 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 ammo-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 2 ) in the form of ammonia 

 from the ammo-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 deamination (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. In any case it 

 is to such ammonium compounds as have been already mentioned as 

 being transformed into urea when circulated through an excised liver 

 (p. 574) that we have to look for the source of a portion, and probably 

 a large portion, of the urea. Ammonia in the form of carbonate or 

 carbamate is constantly found in the blood (p. 575). 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 amino-acids with libera- 

 tion 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 deamidization 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 deamidization in the cells takes its place as a source of energy 

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

 back into the blood, and may thus be carried to the liver for conversion 

 into urea. It is not necessary, however, to suppose that all of the 

 nitrogen must perforce make this journey before being changed into 

 urea. There is evidence that all the tissues share to some extent with 

 the liver the power of forming urea just as they share with the liver the 



