CHAPTER LXXII 

 THE METABOLISM OF PROTEIN (Cont'd) 



CREATINE AND CREATININE 



Creatine and creatinine are very largely products of endogenous metab- 

 olism; they are mainly derived from chemical processes occurring in 

 the tissues although some of the creatine and creatinine present in the 

 food may appear as creatine in the urine. 



Essential Chemical Facts 



Before we proceed to discuss the metabolism of these important substances, it will 

 be necessary to refer briefly to some points in their chemistry. The simpler of the 

 two bodies is creatine, which is methyl-guanidine-acetic acid ; creatinine is its anhydrid, 

 being formed from creatine by the removal of a molecule of water, so that the NH, 

 groups become joined together in the same way as they do in the formation of pep- 

 tides from amino acids (page 636). The relationships are illustrated in the following 

 formulas : 



CH, - N - CH - CO 



(methyl) " , , 



CH-N 



/ \ 



/ CH 2 COOH NH = C 



NH = C - H..O = \ 



\ (acetic acid) - \ 



\ \ 



(guanidine) NH 2 NH 



(creatine) (creatinine) 



It should be noted that guanidine is closely related to urea, O=C(NH a ) 2 , and that 

 when creatinine is formed from creatine a ring formation occurs, giving what may be 

 regarded as an imidazole derivative (see page 639). Creatine is also related to one 

 of the important diamino acids, arginine, since both contain guanidine radicles, NH 

 C(NH 2 ),, and to histidine and the purines (see page 669), both 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 methyl- 

 "[STTT r\TT 



amino-acetic acid (CH < U 3 ), also known as sarcosine. 



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 normal 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 



656 



