504 A MANUAL OF PHYSIOLOGY 



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. It is now known that the greater part of 

 the urea, at any rate, does not come from tissue-protein, either by 

 hydrolysis or by oxidation, but that much of it arises by the synthesis 

 of decomposition products of the food -proteins simpler than itself 

 viz., such ammonium compounds as have been already mentioned as 

 being transformed into urea when circulated through an excised 

 liver (p. 501). Ammonia in the form of carbonate or carbamate is 

 constantly found in the blood, and the portal blood contains normally 

 three to five times as much ammonia as arterial blood. Unquestion- 

 ably, then, a portion of the urea, and probably a large portion, 

 is formed from such ammonia compounds, and if we still ask where 

 these compounds arise, and what their immediate precursors are, 

 the only reply which can be given is that ammonia is known to be 

 one of the products of the digestion of proteins, and that there is 

 some evidence that in certain ways the amide (NH 2 ) groups can be 

 split off from amino-acids and then utilized as ammonia for the 

 formation of urea. The decomposition products of the food-pro- 

 teins absorbed from the intestine are thus clearly indicated as a 

 source of urea namely, of that large fraction which represents the 

 surplus nitrogen eliminated without entering into the metabolism 

 of the cells. It is of importance to remark that such hydrolytic 

 cleavages as are associated with the splitting of protein into amino- 

 acids, etc., only slightly reduce the available energy of the com- 

 pounds. If, as is most probable, the liberation of the nitrogen from 

 the amino-acids is also accomplished by hydrolytic cleavage, the 

 residue, relatively rich in carbon, will still be available for yielding 

 to the body by its oxidation an amount of energy not much less than 

 could be obtained from the original protein. 



The combination of ammonia with carbon dioxide and the con- 

 version of the carbonate into urea does not require any oxidation. 

 But if, as there is every reason to believe, a part of the carbonaceous 

 residue is converted into carbo-hydrate, a certain amount of oxida- 

 tion must occur in the transformation. It would be an error to 

 suppose that all the ammonia or other forerunners of urea come 

 from the intestine, or, indeed, that all the urea is manufactured in 

 the liver. Urea does not entirely cease to be produced when the liver 

 is removed. Some of the urea may be formed ' on the spot,' so 

 to speak, in the endogenous metabolism of all the tissues, and 

 perhaps by a different process from the hepatic urea and from 

 different intermediate substances. 



Such compounds as guanin, sarkin or hypoxanthin, xanthin, uric 

 acid, and kreatin, used to be cited as among the possible intermediate 

 substances. But while there is now complete evidence that the 

 first three bodies can be and are converted into uric acid, there is no 

 reason to believe that they are stages on the way to urea. Uric acid 

 is, indeed, very closely related to urea, and can be made to yield it 

 by oxidation outside the body. Not only so, but it is, in part at 

 least, excreted as urea when given to a mammal by the mouth, 

 and it replaces urea as the great end-product of nitrogenous meta- 

 bolism almost wholly in the urine of birds and reptiles, and partially 



