626 METABOLISM 



A similar replacement of some of the creatinine by creatine appears 

 when carbohydrate is entirely withheld from the diet, or in diabetic 

 animals, either in the disease diabetes mellitus in man or in the experi- 

 mental condition induced in animals by giving phlorhizin. Unfortu- 

 nately, in a considerable part of the work that has been done on this 

 phase of the subject a method of estimation was employed which did not 

 take sufficiently into account the influence of acetoacetic acid on the 

 creatine estimation; but even after allowing for this possible source of 

 error, there can be no doubt that creatine appears in the urine when 

 carbohydrates are improperly metabolized. If carbohydrates are given 

 to a starving animal, for example, the creatine is replaced in its urine by 

 creatinine, although this will not occur when either protein or fat is fed. 

 The general conclusion which may be drawn from these observations is 

 that carbohydrates in some way are required for the proper conversion 

 of creatine into creatinine in the animal body (Cathcart) 37 . 



Origin of Creatine and Creatinine 



Notwithstanding the amount of excellent work that has recently been 

 done on the metabolism of creatine and creatinine, w,e know very little 

 indeed regarding the origin of these bodies in the animal organism. It 

 would be profitless to discuss this problem to any great extent, but a 

 few of the most important facts so far established may be of interest and 

 of value. The first step in attacking such a problem is to compare the 

 amounts present in the various organs and tissues, in the blood, and in 

 the excreta. Of the approximately 12D grams of creatine and creatinine 

 in the body of an average adult, a very large proportion is in the muscles, 

 the voluntary muscles containing the largest percentage, 'the heart con- 

 taining a medium percentage, and the involuntary (intestinal) muscles 

 containing relatively a small amount (Myers and Fine) 38 . Next to the 

 skeletal muscles, and containing more than the involuntary mus- 

 cles, come the testis and brain. The liver, pancreas, thyroid, kidneys, 

 spleen, etc., contain traces, the smallest amount of all being found in the 

 blood. 



In all these places by far the greatest proportion of the total creatine- 

 creatinine exists as creatine, which is exactly the reverse of the condi- 

 tion obtaining in the urine of adults, where practically all is excreted as 

 creatinine. The close chemical relationship between creatine and creat- 

 inine, considered along with the above facts regarding their quantitative 

 distribution in the body, indicates that the creatinine of the urine is de- 

 rived from the creatine of the tissues. The question is, How does the 

 creatine come to be converted into creatinine? Such a transformation is 



