272 PRINCIPLES OF GENEkM. PHYSIOLOGY 



but point out the importance of the ratio of carbon to nitrogi-n and of caloric.-, 

 to nitrogen, as indicating normal or perverted protein metabolism. In twelve out 

 of eighteen, the values were normal, in six they were high. In these six, tlinv 

 was practically no lactic acid and no reducing power to indicate disturbance 

 of carbohydrate oxidation, so that the result must be considered to be due to 

 abnormal protein metabolism. Such substances as creatinine, uric acid, amino- 

 acids would account for the increase of the carbon to nitrogen ratio above the 

 normal, where it is given chiefly by urea and ammonia. 



There is general agreement that the source of the energy in muscular work is 

 the oxidation of carbohydrate, which will be discussed in the next section of this 

 chapter. At the same time, it is extraordinary that there should be so little evidence 

 of increased wear and tear of the nitrogen-containing machinery of the cell. 



What explanation can be suggested for this fact? To begin with, although 

 excessive work may be looked upon as pathological, the fact that uric acid is 

 increased in such a condition suggests that there is always an increase of the 

 endogenous protein breakdown due to wear and tear, since the result of excessive 

 work is probably to be regarded merely as an exaggeration of a particular phase 

 of the chemical reactions involved in the whole process of contraction and restitu- 

 tion. Moreover, analysis of muscle itself after work has shown that the purine 

 content is increased (Burian, 1905, M'Leod, 1899), while Brown and Cathcart 

 (1909) and Pekelharing and Van Hoogenhuyze (1910) found an increase of creatine. 



Hermann (1867, p. 100 of the first part) distinguished between two processes 

 in muscle, the one the contraction process, by which energy is given out, associated 

 with the production of carbon dioxide, lactic acid and a nitrogenous compound, 

 called provisionally " myosin " ; the other process is associated with a using up of 

 the tissue itself, giving rise to carbon dioxide and creatine. The restitution of 

 the energy-affording material of high chemical potential is effected by the aid 

 of oxygen, and makes use of the nitrogenous product of the breaking-down process 

 " myosin " and probably also of the lactic acid. The restitution of the tissue 

 structure itself requires the supply of some nitrogenous material from without 

 Hermann says " protein," we should now prefer to say amino-acids or purines. 

 Oxygen is of course required. The resemblance of this view to that associated with 

 the names of Fletcher and Hopkins, which they have established by a large 

 number of experiments, and shown that the contraction itself is a double pr< > 

 is great, as we shall see later ; the point to be noticed here is the difference 

 between the nitrogenous metabolism in the two kinds of change; the normal 

 contraction results in the separation of a substance which is used up again with 

 the aid of energy derived from an oxidation process of some kind, whereas the wear 

 and tear of the machine itself gives off such nitrogenous compounds as creatine or 

 uric acid, etc., which are excreted and must be replaced by new material. 



The name "ntogen" for the complex substance of high energy content was first used l>v 

 Hermann, and will be found on p. 79 of the third part of the book above referred to. The 

 statement is made there that it was suggested in the second edition of the same author's 

 " Grundriss der Physiologic des Menschen," Berlin, 1867. 



In starvation, the heart while continually at work, does not lose weight ; so that 

 it must be able to utilise nitrogen derived from the other tissues. In Cathcart's 

 experiments (1909), already mentioned, the appearance of creatine in starvation 

 was made use of to investigate the problem of resynthesis. It was assumed that 

 its escape was due to the absence from the tissues of some material which normally 

 caused its retention. It was found to disappear if carbohydrate food was given, 

 but not if either protein or fat without carbohydrate was given. The appearance of 

 creatine is, according to this worker, to be regarded merely as an index of failure 

 of resynthesis, which process only takes place in the presence of carbohydrate. 



We saw above (page 269) how important the function of carbohydrate is 

 in the synthesis of protein, so that the hypothesis in its application to muscle 

 is in accordance with other known facts. 



As to the nature of the chemical changes concerned in this synthesis of protein under the 

 influence of carbohydrate we have, at present, little more than suggestions. We know that 

 simple aldehydes form compounds with ammonia, and it seems more than likely that amino- 





