THE METABOLISM OF PROTEIN 623 



formation occurs, giving what may be regarded as an imidazole deriva- 

 tive (see page 604). Creatine is also related to one of the important 

 diamino acids, arginine, since both contain guanidine radicles, 



NH 2 



/ 

 (NH=C ), and to histidine and the purines (see page 634), both 



NH 2 



of which contain the imidazole ring. The close relationship which 

 creatine bears to urea is illustrated by the fact that urea is formed 

 when creatine is subjected to the action of boiling barium hydrate. When 

 it is oxidized by means of potassium permanganate, urea is also formed, 

 the remainder of the molecule, more or less intact, being split off as 



NH;-CH 3 



rnethyl-amino-acetic acid (CH 2 ), also known as sarcosine. 



COOH 



The conversion of creatine to creatinine goes on slowly in aqueous 

 solutions, but is much accelerated by heating with acid. Heated in an 

 autoclave at a temperature of 117 C. for thirty minutes, with half nor- 

 mal hydrochloric acid, the creatine goes over almost quantitatively into 

 creatinine. It will be noted that the creatinine ring is partly oxidized. 

 This renders it unstable, so that creatinine in the presence of alkalies 

 has the power of reducing metallic oxides. Like glucose it can reduce 

 alkaline solutions of copper, silver and mercuric salts; it also reduces 

 picric acid in weakly alkaline solution to picramic acid, which, being red, 

 furnishes us with a solution the strength of which can be estimated 

 colorimetrically. 



Quantitative Estimation. Although the presence of creatinine in the 

 urine has been known for many years, there being from 1 to 2 grams of 

 it in the twenty-four-hour urine, little progress was made in the study 

 of its metabolism because of the absence of a reliable method for its 

 estimation. The elaboration by Folin of a colorimetric quantitative 

 method for creatinine, depending on the reduction of picric acid, has 

 furnished the starting point for the modern work which has been done. 

 To estimate the creatine by this method, it is usual to proceed as fol- 

 lows: The creatinine content is first of all determined, another portion 

 of urine being then heated with acid in the autoclave until all of its 

 creatine has been converted into creatinine. A second determination of 

 creatinine is then made, and the difference between the two is calculated 

 as creatine. 



