776 PHYSIOLOGY OF DIGESTION AND SECRETION. 



of the body. It is known, for instance, that the percentage of 

 ammonia compounds in the tissues is greater than in the blood. 

 Since the cells of many of the protein tissues of the body contain 

 intracellular enzymes capable of causing hydrolytic cleavage of the 

 protein molecule it is probable that some ammonia may be thus 

 formed in various parts of the body; and so far as it is produced 

 it will be converted to urea by the action of the liver and possibly 

 by a similar action in other tissues. 



2. Urea arises from the monamino-acids by a process of deami- 

 dization, whereby the NH 2 group is converted to ammonia and 

 then probably to urea. It is known, for example, that when a 

 monamino-acid such as glycocoll or leucin is given to an animal the 

 nitrogen of the compound is promptly eliminated as urea. Since, 

 as stated above, these monamino-acids form the chief constituent 

 of the end-products formed in the digestion of proteins, it is very 

 probable that in passing through the liver their nitrogen is removed 

 by a process of deamidization and eliminated as urea. The organic 

 acid radicle that remains may suffer oxidation and thereby furnish 

 heat energy to the body, or it may possibly be stored after synthesis 

 as carbohydrate (glycogen) or as fat. Doubtless also in the met- 

 abolism of the proteins of the tissues, as in the digestion of the 

 food proteins, monamino-acids are likewise formed and suffer a 

 similar fate, -so far as the nitrogen is concerned. 



3. Urea arises from the diamino bodies (arginin), formed in the 

 cleavage of the protein molecule, by conversion of the contained 

 guanidin radicle. Kossel and Dakin * have demonstrated the 

 existence of a ferment, arginase, which is capable of splitting 

 arginin into urea and ornithin. The reaction may be represented 

 by the following equation: 



NHC<^ 2 (CH 2 ) 3 CHNH 2 COOH + H 2 O - CO<*Jg 2 + NH 2 (CH 2 ) 3 CHNH 2 COOH 



Arginin (guanidin diamino-valerianic acid. Urea. Diamino-valerianic acid. 



Unlike cases 1 and 2 the urea in this instance is formed directly 

 from the guanidin residue contained in the arginin. Since this 

 latter substance constitutes one of the split-products of the protein 

 during digestion and probably also one of the split-products in 

 the metabolism of the proteins of the tissues, there is reason to 

 believe that part of the urea actually formed in the body arises 

 by this method. 



4. Urea arises from a further metabolism of uric acid. As is 

 stated below in describing the history of the origin of uric acid 

 there is positive evidence that not all of the uric acid produced 

 in the body is excreted as such. A portion is further acted upon 

 by a uricolytic enzyme and converted to urea. The portion so 



* 'Zeitschrift f. Physiol. Chemie," 1904, xlii., 181. 



