PROTEIN METABOLISM 867 



It may be formed from this latter substance by boiling for three hours 

 with strong hydrochloric acid. Creatine has long been known as the 

 most abundant nitrogenous extractive in the body. It exists in 

 relatively large quantities in muscle, and in meat extracts, such as 

 Liebig's, it occurs to the extent of 10 or 12 per cent. It has been 

 calculated that the body of a man at any time contains about 90 grin, 

 of this substance. On boiling creatine with baryta water it undergoes 

 hydrolysis with the formation of urea and sarcosine or methyl glycine. 



CH 3 CH 3 



NH. NH 2X 



)C.N.CH 2 COOH + H.,0 = >CO + HN.GH 2 COOH 



NH/ NH/ 



Creatine Urea Methyl glycine 



Owing to the ease with which this formation of urea from creatine 

 may be brought about outside the body, it was natural that this 

 substance should be regarded as an important precursor of the urea 

 in the urine. The view was held till recently, however, on the ground 

 of experiments by Voit, that creatine administered in the food appeared 

 in its entirety as creatinine in the urine, so that if creatine were 

 liberated from the muscles in their normal processes of metabolism 

 it would pass to the kidneys and be excreted as creatinine without 

 undergoing further decomposition. On this account too the creatinine 

 in the urine was regarded as derived almost exclusively from the 

 creatine taken in with the food. The analyses given in Folin's tables 

 show that in one respect at any rate this view was incorrect. Creati- 

 nine is excreted in considerable quantities even when the man is on 

 a creatine-free diet, or even when his food is almost free from protein. 

 It has been found moreover by Folin that creatine administered by 

 the mouth may be entirely oxidised in the body. This is especially 

 the case if the animal or man is on an insufficient protein diet. In 

 most cases a certain proportion escapes decomposition and causes an 

 increase in the quantity of creatinine. Under abnormal circum- 

 stances, e.(j. during illness, when the physiological activities of the 

 body are lowered, a portion of the creatine may be found in the urine 

 in an unchanged condition. We might expect to find therefore that 

 if the creatine of the muscles as the result of their disintegration be 

 discharged into the blood, a portion of it would undergo complete 

 oxidation with the formation of urea, while the other part in a healthy 

 individual would appear in the urea as creatinine, and a small propor- 

 tion under conditions of diminished vitality might pass unchanged. 

 If creatinine is to be regarded in any way as the index of tissue meta- 

 bolism its amount ought to vary with the extent of this metabolism. 

 Thus it should be increased when there is an exaggeration of the 



