THE METABOLISM OF PROTEIN 657 



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

 tions 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 follows: 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 de- 

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

 as creatine. 



It should be pointed out that, since the creatine is estimated by an indirect method, 

 there are considerable chances for inaccuracy. Indeed, it has been shown that errors 

 may have been incurred in some of the recent work on account of the fact that when 

 aeetoacetic is present in the urine it prevents the creatinine from developing its 

 full reducing power on picric acid in the cold, so that when subsequently the urine is 

 heated with acid for the purpose of converting the creatine into creatinine, the 

 destruction of aeetoacetic acid allows the reducing power of the creatinine to develop 

 to full intensity. It is obvious that this would make it appear as if creatine had been 

 converted into creatinine. It is particularly in the urine of diabetic patients, in which 

 aeetoacetic acid is present that mistakes are likely to be made. 



Metabolism 



When we come to consider the metabolism of creatine and creatinine, 

 we find that there are remarkably few facts definitely known concerning 

 it. The average amount excreted daily, expressed as the number of milli- 

 grams of creatinine in twenty-four hours per kilogram body weight, 

 is known as the creatinine coefficient (Shaffer). 36 For a lean person this 

 is about 25 mg. ; for a corpulent person, about 20 mg., the difference in- 

 dicating that muscle mass, and not body weight, is the important factor 

 determining the coefficient. Further evidence that this relationship ex- 

 ists is furnished by the fact that in the muscular atrophies creatine ex- 

 cretion is distinctly below normal. It must be the mass of the muscles 

 rather than their activities that is the determining factor, for the creatine 

 excretion does not become increased by muscular exercise. 



Influence of Food, Age, and Sex. Although creatine and creatinine are 

 endogenous metabolites, it must be remembered that, under ordinary 

 dietetic conditions, a part of each is derived from these substances pres- 

 ent in the food. It is important therefore to consider the conditions 

 under which the creatine and creatinine in the food appear in the urine. 

 Regarding creatinine, it is pretty well established that practically all 

 that is taken with the food reappears as creatinine in the urine. Shaffer 



