866 PHYSIOLOGY 



There is one other method in which urea may be formed by a rapid 

 alteration of the proteins taken in with the food. Nearly all the 

 ordinary proteins contain arginine as an integral part of their 

 molecule. This substance can be regarded as formed by a coupling 

 of guanidine with amino-valerianic acid and as analogous to the most 

 prominent extractive of muscle, namely, creatine, which is methyl 

 guanidine acetic acid. On beating either of these substances with 

 baryta water it undergoes hydrolysis and is decomposed with the 

 formation of urea and, in the case of arginine, a-S-diamino-valerianic 

 acid ; in the case of creatine, methyl amino-acetic acid or sarcosine. It 

 has been shown by Dakin and Kossel that the same change may be 

 effected under the agency of a ferment, arginase, which is contained 

 in extracts of the intestinal wall or of the liver. We have every reason 

 to believe therefore that a certain small proportion of the urea which 

 appears in the urine after the ingestion of protein is due to this hydro- 

 lytic splitting of the arginine contained in the protein molecule. The 

 other moiety of the arginine, namely, the diamino-valerianic acid, 

 probably undergoes the same changes as the other amino-acids, such 

 proportion of it as is not required for the building up of the tissues of 

 the body being deaminised and giving rise to urea and some CHO group 

 in the manner already discussed. 



THE ENDOGENOUS OR TISSUE METABOLISM OF PROTEINS 



On comparing the output of the various nitrogenous excreta 

 given in Folin's tables quoted above (p. 855), we see that on a low 

 protein diet, when the exogenous or energy metabolism of this food- 

 stuff is reduced to a minimum, the only substance which does not 

 undergo simultaneous diminution is the creatinine. Whereas on 

 an ordinary diet free from meat it only accounts for about 

 3 per cent, of the total nitrogen output, on the low diet it contains as 

 much as 17 per cent. The conclusion at once suggests itself that 

 creatinine, more than all the other constituents of the urine, must be 

 regarded as an index of the tissue metabolism of protein. Let us see 

 what facts can be adduced in favour of this view. 



Creatinine has the formula : 



NH = C.N(CH 3 ).CH 2 



NH - - CO 



and may be regarded as derived by a process of dehydration from 

 creatine (methyl guanidine acetic acid). 



NH = C.N(CH 8 ).CH 2 COOH 

 NH, 



