Theories Of Protein Metabolism

Before the formulation of the theory which I shall presently indicate, and which is generally accepted as correct, three important hypotheses had existed.

(1) Liebig's

This scientist maintained that protein is the sole source of muscular work, the carbohydrates and fats being the sources of heat, and that the economy must obtain all protein in a preformed condition, as being unable to synthesise it from simple crystalline products. This view was shattered by the experiment of Fick and Wislicenus, who in the ascent of the Faulhorn in 1865 subsisted solely on non-nitrogenous food, and found that the nitrogen excreted indicated a metabolism of protein quite insufficient to have produced anything like the energy represented by the work done in their climb.

(2) Pfliiger's

He held that all the nitrogen excreted as urea had been during the previous twenty-four hours an integral part of the living tissues, and that it had been derived from the food previously absorbed. In other words, all the protein katabolised had been first formed into bioplasm, and was then by a process of oxidation converted into urea even during overfeeding with meat.

(3) Voivs

This consists in the statement that the protein of the absorbed food passes to the living tissues, and is there katabolised without first becoming an integral portion of the latter. Thus the living tissue which consists of "organised" protein is bathed or suspended in a solution of "circulating protein," and the chemical decompositions that constitute protein katabolism take place only in solution.

It is hardly conceivable on the one hand how the extremely large quantities of food protein which are known to be kata-bolised in the twenty-four hours could have been built up into the tissues and as rapidly burned away, or, on the other, just how the proteins in the blood could definitely reach all the tissues of the body and come into contact with them without becoming an integral portion of their substance.

The whole subject has been recently most carefully reviewed by Folin, who points out that no fundamental theory concerning protein metabolism can be accepted unless it can be made to harmonise with the laws governing the composition of the urine. Now, "normal urine," as understood by the text-books, is that urine excreted after feeding on the diet usually known as the Voit standard diet. The whole misconception as to metabolism and certain dietetic theories reared thereupon are due to the tacit acceptance of Voit's standard of 118 grams of protein, which most authors and scientists have copied without taking the trouble to verify. They have even persisted in doing this after it was demonstrated that nitrogenous equilibrium was possible on one-third of the protein of the above standard. Folin, therefore, made a study of human urines obtained from diets as different as possible from the so-called standards of diet - some being vegetarian, some purely carbohydrate, etc.

In this study he elicited the fact that the composition of urine representing 15 grams of nitrogen, i.e., 95 grams of protein, differs very widely from the composition of urine representing 3 or 4 grams of nitrogen, i.e., 25 grams of protein, and that there is a gradual and regular transition from one to the other. To explain such variations he thinks that we must assume that there are two forms of protein katabolism essentially independent, and quite different - the one variable in quantity, the other constant. The former chiefly yields urea and inorganic sulphates, no creatinin, and probably no neutral sulphur. The latter or constant katabolism is largely represented by creatinin and neutral sulphur, and to a less extent by uric acid and ethereal sulphates.

The fact that creatinin elimination is not diminished when practically no protein is administered with the food, and that the elimination of some of the other constituents is only slightly reduced under such conditions, explains why a certain amount of protein must be furnished with the food if nitrogen equilibrium is to be maintained. The metabolic processes resulting in the end-products which tend to be constant in quantity appear to be indispensable for the continuation of life, and this he calls tissue or endogenous metabolism. The other or variable protein metabolism he calls exogenous or intermediate.

The key to endogenous metabolism is the elimination and physiological significance of creatinin: and in addition to the researches of Folin much work has been done on this subject by Mendel and his pupils. The facts elicited may thus be summarised. Plants contain no creatin or creatinin, but these substances are found in the tissues, especially the muscles, of all vertebrate animals. Hence there must be endogenous and exogenous creatinin elimination. Creatinin is excreted in the urine during starvation in patients on a vegetarian diet, and is always a constant quantity, different for different individuals, but quite independent of the total amount of nitrogen eliminated. It varies with the weight of the individual, and muscular persons excrete a greater proportion than those inclined to adiposity, proving that bulk of muscle is a factor in the amount excreted. The most abundant extractive of muscle is creatin, which is closely allied to creatinin, the latter being formed by dehydration of the former. It is assumed, therefore, that in normal metabolism creatin is continually produced and converted into creatinin, and that this is rapidly eliminated. Besides creatin probably urea and water in small quantities are formed in the muscles, and if it were known just how much urea - if any - was formed from the same katabolic processes that form creatin, then endogenous metabol sm could be more definitely estimated.