METABOLISM OF PROTEINS 599 



there is other evidence pointing in the same direction ; for example 

 in ordinary circumstances creatin is either absent from the urine or 

 present in very small amount, except in young children. When, how- 

 ever, the decomposition of tissue-protein is abnormally increased, as in 

 starvation, in fevers, in women after delivery, while involution of the 

 uterus and the associated destruction of a considerable mass of smooth 

 muscle is taking place, creatin appears in larger quantities in the urine, 

 perhaps because it can no longer be all converted into creatinin. Now, 

 the increased excretion of creatin in starvation can be prevented by 

 giving carbo-hydrate food, which is known (p. 606) to lead to sparing 

 of tissue-protein (Mendel and Rose). That the depletion of the body 

 of carbohydrate is in some way related to the elimination of creatin 

 is further shown by the fact that creatinuria is associated with diabetes 

 and with the action of substances like phlorhizin, hydrazin, phosphorus, 

 etc., all of which cause carbo-hydrate deficiency. Something more is 

 involved, however, for under conditions of diet which produce acidosis 

 (an increase in the hydrogen-ion concentration of the blood), creatin 

 appears in the urine no matter how rich the food may be in carbo-hy- 

 drate. For example, a diet of oats and maize, which are typical acid- 

 producing foods, causes creatinuria in rabbits, which promptly disappears 

 when carrots, a base-producing food, are added (Underhill). 



The statement that the content of the urine in creatinin is increased 

 by muscular work may indicate that the muscular machine wears out* 

 faster during activity than during rest, or perhaps only that already- 

 formed creatin leaves the muscles in greater amount when the blood-flow 

 in increased; but recent observations tend to show that this statement 

 may require revision. 



As to the manner in which creatin is changed into creatinin in the 

 body, a highly suggestive fact is the presence of ferments in various 

 organs which possess this power. Ferments also exist which can 

 decompose both creatin and creatinin. The existence of such enzymes 

 is presumptive evidence that the changes which they are capable of 

 producing actually occur in the organism ; but the seat of the changes 

 if they do take place, and their metabolic significance, are unknown. 

 Creatin when given by the mouth or injected into the blood does not 

 cause any increase in the urinary creatinin, nor when administered in 

 moderate quantities does it seem to be excreted as creatin. Like urea, 

 creatinin, and amino-acids, it is taken up very rapidly by the muscles. 

 Creatinin, on the other hand, when added to the food, causes an increase 

 in the creatinin of the urine. 



Intracellular Ferments Autolysis. As to the agencies by which 

 the decomposition of the proteins is carried out in the cells, we have 

 already spoken of the oxidizing cell ferments, or oxydases (p. 272). 

 Reducing ferments, or reductases, are also known, and can be ex- 

 tracted from most organs, if not all. Like oxydases, they act in a 

 weakly alkaline medium, causing in the presence of hydrogen such 

 reductions as the formation of nitrites from nitrates. There is some 

 evidence that one and the same ferment may act as an oxydase or 

 a reductase according to the conditions. Recent researches have 

 brought to light in addition hydrolytic intracellular ferments, which 

 split up proteins very much in the same way as the proteolytic 

 ferments of the digestive juices. 



The significance of these autolytic enzymes in the normal metabo- 



