PRESIDENTIAL ADDRESS. 305 



it, may act as a sort of food. He arrived at this view on account of the dis- 

 appearance of creatin when fed by the mouth ; but the demonstration by 

 Meilanby and Twort^'' that creatin is broken down in the alimentary canal, 

 deprives these experiments of much di their value. 



Lefm<ann28 after subcutaneous injection in dogs, recovered only a small 

 amount of creatin in the urine, and although his conclusion that there is no 

 conversion to creatin has been criticised by Van Hoogenhuyze and Verploegh, 

 there seems to me to be an increasing amount of evidence in favour of Folin's 

 theory of the utilisation of creatin. 



Cathcart^" showed the important fact that the administration of carbo- 

 hydrates to a fasting man stops the excretion of creatin and that, where carbo- 

 hydrates cannot be used, as in diabetes, creatin appears in the urine.'" 



The explanation that the result is due to the presence of diacetic acid is, as 

 Cathcart and Orr^' showed, not tenable. 



The work of Loewi in 1902, as Liithje pointed out, showed that while the 

 amino-acid products of pancreatic digestion of proteins when eaten along with 

 carbohydrates bring about an actual retention of nitrogen, when fed with fats 

 alone they fail to do so. 



The indications, then, seem very clear that carbohydrates are essential for 

 the .synthesis or re-synthesis of the protein molecule and, if creatin is a potential 

 anabolite yielding the necessary guanidin, the presence of carbohydrates is 

 probably essential for its use in this way and in their absence it must be 

 excreted. 



This view, as far as it concerns the total nitrogen and muscle, I ventured 

 to formulate as far back as 1887, and I then attempted' to represent it 

 diagrammatically.'^ 



The adoption of this view does not invalidate the idea that the formation of 

 creatin is primarily to de-toxicate an excess of free guanidin. The same thing 

 is seen in the behaviour of lecithin, which is manifestly an anabolite, but which 

 seems to have the power of rendering the toxic cholin innocuous. 



'J'Ae Relationship of Creatin and Creatinin. 



The importance of the lengthy and voluminous discussion on the relation- 

 ship of creatinin to creatin seems to me to have acquired an exaggerated 

 importance. 



In the bird the creatin in the urine represents the ordinary overflow of the 

 creatin from muscle which is not used for reconstruction. In mammals this 

 is represented by creatinin, but when the disintegrative changes are increased 

 or the anabolic processes interfered with, then creatin appears along with 

 creatinin. 



The non-conversion, or only small conversion of creatin injected or taken 

 by the mouth, to creatinin, does not appear to be opposed to the view that the 

 latter is formed from the former. The total formation of creatinin in man is 

 only about 1 grm. p^r diem, one ninetieth of the total creatin in the body. If 

 this small conversion is all the body has daily to provide for, it is not to be 

 expected that the demand for a sudden increased conversion will be met, 

 and hence it i« only natural that unconverted creatin should escape 

 if it is administered even in small amounts. The normal occurrence of creatin 

 in the urine of young children seems to indicate that its conversion to creatinin 

 is a function somewhat late in development. 



There is some evidence that the power of conversion is different in different 

 individuals. Thus we found that after a pound of beefsteak with about 

 l-T.Ecrm. of creatin expressed as creatinin, one member of the teaching staff showed 

 a rise of 0-53 grm. of creatinin and 0-2 grm. of creatin, another a rise of 0-49 

 grm. of creatinin and 0177 of creatin, .while two others showed no rise in the 

 creatinin, one showing an increase of 0'425 grm. and the other of 0'213 grm. in 

 the creatin excreted. 



The question may be asked, why should the neutral creatin be converted 

 into the strongly basic crea,tinin ? The relative solubility of the two substances 

 is a possible explanation of this. Creatin is about one-tenth as soluble as 

 creatinin. 



