In this conception of proteid metabolism, we picture the different organs and tissues of the body as being permeated by a fluid which carries variable amounts of nutritive material, the quantity of the latter determining in a way the extent of the proteid katabolism which shall take place. As the proteid of the food passes into the blood and lymph, the fluids bathing the cells are correspondingly enriched, and as a result, proteid katabolism is accelerated in parallel degree. During hunger, on the other hand, the organized proteid of the tissue cells is gradually liquefied and passes out into the current of the circulating fluids. As before stated, the organized proteid as such is never decomposed; it must first enter into solution, and then under the influence of the living cells it undergoes disruption in the same manner as the circulating proteid. It is thus evident that the tissue cells and the circulating fluids permeating them bear an ever changing relationship to each other. Excess of circulating proteid will be attended by increased katabolism, while at the same time there may be some accumulation of proteid in the cells, and indeed some conversion into organized proteid. During fasting, hunger, or with an insufficient intake of proteid food, the current will naturally be in the opposite direction, and organized proteid will slowly, but surely, be drawn upon.

Again, we may ask in view of these facts, of what real use to the body is this large katabolism of circulating proteid? We can easily understand the need of proteid to supply the loss incidental to the breaking down of organized or true tissue proteid, but this we are led to believe is very small in amount. Is there any real need for proteid beyond this requirement? The physiological fuel value of proteid is no greater than that of carbohydrate and considerably less than half that of fat, consequently there is on the surface no apparent reason why proteid should be used for its energy value in preference to the non-nitrogenous foodstuffs. Further, as we have seen, the energy of muscle work comes mainly, at least, from the breaking down of fat and carbohydrate; proteid, in the case of the well-nourished individual, ordinarily playing no part in this important line of energy exchange. Lastly, in the katabolism of proteid there is the large proportion of nitrogenous matter to be split off and disposed of before the carbon moiety of the molecule can be rendered available. Here, we have involved not only a loss of energy, but in addition a certain amount of what appears to be useless labor thrown upon the liver, kidneys, and other organs. Is there any wonder that the thoughtful physiologist, looking at the facts and theories presented by the Voit conception of proteid katabolism, should ask wherein lies the value to the body of this high rate of metabolism of circulating proteid, a rate of metabolism which is seemingly governed primarily by the amount of proteid food ingested?

Turning next to Pflüger’s[51] views regarding proteid katabolism, we find a totally different outlook. Here, the supposition prevails that the plasma of the blood and lymph, with its contained proteid, is the food of the organs or their cells, but that before this food material can undergo katabolism it must first be absorbed by the cell and built up into the living protoplasm of the tissue. In other words, according to the views expressed by Pflüger, katabolism must be preceded by organization of the proteid. Expressed in still different language, the proteid material circulating in blood and lymph must be eaten up by the hungry cells and, by appropriate anabolic processes, made an integral part of the living protoplasm before disassimilation can occur. Further, according to Pflüger’s conception of these processes, there is a radical difference in the chemical nature of living protoplasm as compared with that of the so-called circulating proteid. The latter is looked upon as being comparatively stable, resisting oxidation in high degree, and hence not prone to undergo metabolism. Living protoplasm, on the other hand, is characterized by instability, suffering oxidation with the greatest ease, and hence readily broken down in the ordinary processes of katabolism. Assuming for the moment the correctness of this theory, we see at a glance that all disruption of proteid matter in the body must be preceded by the upbuilding of the proteid into living protoplasm. There can be no destruction of proteid until the latter has been raised to the high plane of living matter. The dead, inert circulating proteid can serve simply as food for the living cells, and cannot undergo katabolism until it has been built up into the organized structure of the tissue or organ. Even though we grant that a small proportion of proteid may suffer katabolism without previous organization, it does not materially modify the general trend of the argument that, according to Pflüger’s hypothesis, proteid katabolism is essentially a process involving the disruption of living protoplasm.

Consider what this means in the light of facts already presented. Remembering that the one factor above all others influencing the rate of proteid katabolism is the amount of proteid food taken in, and that the output of nitrogen, no matter what the previous condition of the body or the amount of proteid food ingested, runs more or less parallel with the consumption of proteid, we are forced to the conclusion, in accepting this hypothesis, that there must be superhuman activity in the building up of living protoplasm, only to be followed, however, by its immediate and more or less complete breaking down. Further, think of the daily or periodical fluctuation in the construction of bioplasm, coincident with variations in the amount of proteid food consumed, and the corresponding destruction of bioplasm as indicated by the daily output of nitrogen. Imagine, if you will, the concrete case of a man of 70 kilos body-weight eating a daily ration containing 125 grams of proteid, the nitrogen equivalent of which is practically excreted within twenty-four hours, and are we not wise in hesitating to believe that all of that proteid has been so quickly built up into living or organized tissue only to be immediately broken down and thrown out of the body? Think of the enormous activity implied in the manufacture of this bioplasm in the time allotted, and for what? Apparently, so that it can be broken down again. But such energy as is liberated in the breaking-down process might be derived far more economically by simple destruction of the proteid, as contained in the meshes of the tissue elements, without assuming a preliminary conversion into living protoplasm. Obviously, we have here a theory which does not help us in arriving at any very satisfactory conception of proteid metabolism. The facts which Pflüger and his followers bring forward in support of the theory are not very convincing, or at least not sufficiently so to carry conviction in the face of a natural disinclination to believe in the necessity of such a profound anabolic process, merely as a prelude to the speedy destruction of the finished product. Finally, we may add that if all proteid katabolized in the body must first be raised to the high level of living protoplasm before the final disruption can occur, it may be prudent to keep the daily intake of this foodstuff down to a level somewhat commensurate with the real needs of the body.

As has been stated many times in the course of this presentation, the most striking feature of proteid metabolism is the rapidity with which large quantities of proteid consumed as food are broken down, and the contained nitrogen eliminated from the body as urea. A few hours will suffice to accomplish the more or less complete destruction of food proteid; and any theory of proteid metabolism, to be at all satisfactory, must explain this peculiar phenomenon. According to recent investigations, it seems probable that some, at least, of the cleavage products of proteid formed during intestinal digestion are not built up into new proteid, but are at once eliminated mainly in the form of urea, without becoming a part of either the so-called circulating proteid, or the living protoplasm of the body. It will be recalled that under the influence of the digestive enzymes, trypsin and erepsin, proteid foodstuffs may be broken down while undergoing intestinal digestion into monamino- and diamino-acids, such as leucin, tyrosin, arginin, lysin, etc. A certain proportion of these comparatively simple substances may be directly absorbed by the portal circulation and carried to the liver, where they may undergo conversion into urea. In this way, some portion of the nitrogen of the ingested food may be quickly eliminated from the system. As has been stated in another connection, we are not sure at present how far proteid decomposition of the kind indicated takes place normally in the body. We merely know that there are present in the intestine, enzymes capable of splitting up proteid into these small fragments, and that substances of this type when made to circulate through the liver are transformed into urea. These facts, coupled with the well-known tendency of the nitrogen of proteid food to appear in the excretions a few hours after the food in question has been consumed, naturally suggests a direct breaking down of proteid along the lines indicated, with a possible retention of a carbonaceous residue (nitrogen-free) for subsequent oxidation, as a source of energy for heat or work. Obviously, all of the proteid food cannot behave in this manner, for if such were the case there would be no proteid available for making good the normal waste incidental to tissue changes. Either a certain amount of proteid escapes this profound alteration produced by the proteolytic enzymes in question, or else a certain proportion of these simple decomposition products is synthesized in the intestine, or in the tissues of the body, to form new proteid for the regeneration of cell protoplasm. However this may be, we have presented in this view a plausible explanation of the prompt appearance of food nitrogen in the excretions, and without compelling belief in a theory, such as Pflüger’s, which taxes one’s credulity to the utmost. To be sure, as a prominent writer on physiology has recently said, such a view stands opposed to our conceptions of the importance of proteid food; but it seems possible, in the light of accumulating knowledge, that our conceptions of the part played by proteid foods in the nutrition of man have not been strictly logical, or quite in accord with true physiological reasoning.

Again, in this connection, we may ask the question, why is it that the body provides such an effective method for the speedy breaking down of proteid food and the prompt elimination of the contained nitrogen? Whatever the means made use of by the organism in accomplishing this, the result is the same; the nitrogen of the ingested food is, in large measure, quickly gotten rid of. We clearly recognize the all-important position of proteid foods in the nutrition of the body, but there appears a certain inconsistency in this prompt removal of the nitrogen-containing portion of the proteid molecule. The nitrogenous part of the proteid food is, physiologically considered, the all-important part. It is the only source of nitrogen available to the system, and yet apparently the larger proportion of this nitrogenous material is not utilized in any recognizable way, but is eliminated as quickly as possible. Is it not within the limits of possibility that these methods, whatever may be the exact mechanism involved, are merely a means of getting rid of a surplus of proteid for which the body has no real need? This question I shall try to answer later on in another connection, but we may advantageously keep this possibility in mind while we are discussing these theories of proteid metabolism.

It is obvious, in the light of present knowledge, that there must be a certain amount of true tissue proteid broken down each day, independent of that larger metabolism coincident with the intake of proteid food. However much this more voluminous proteid katabolism may fluctuate, owing to variations in the intake of proteid, and whatever the significance of this latter phase of metabolism, it is self-evident that there must be a steady, constant metabolism, upon which the life of the various tissues and organs of the body depends, and by which the proteid integrity of the tissue cells is maintained. This implies a certain degree of true tissue change, in which definite amounts of proteid material are broken down and the resultant loss made good from the proteid intake. No matter what specific name be applied to this form of proteid katabolism, its existence is clearly recognized. It is obviously a form of metabolism distinct, and probably quite different, from that form, more variable in extent, which is associated with the intake of proteid food. Plainly, if there is truth in these statements, there should be some data available by means of which these two lines of proteid katabolism can be more or less sharply differentiated.

Thanks especially to the work of Folin,[52] these data are now apparently at hand, and the facts which he has accumulated with painstaking care seem destined to throw additional light upon our conception of proteid metabolism. It will be remembered that in the breaking down of proteid, the great bulk of its contained nitrogen is eliminated in the form of urea. In addition, a certain smaller amount of nitrogen is excreted in the forms of creatinin and uric acid. As we have seen, the total output of nitrogen, which measures the extent to which proteid is decomposed in the body, varies with the intake of proteid food; but it is found that the proportion of nitrogen excreted in the forms of urea and uric acid varies with the extent of the metabolism. In other words, quantitative changes in the daily proteid katabolism are accompanied by pronounced changes in the distribution of the excreted nitrogen. Let us take a single illustration from Folin’s results; the case of a healthy man who on one day—July 13—consumed a proteid-rich diet, and on the other day—July 20—was living on a diet containing only about 1 gram of nitrogen. The composition of the excretion through the kidneys on these two days is shown in the following table:

July 13.July 20.
Volume of urine1170 c.c.385 c.c.
Total nitrogen16.80 grams3.60 grams
Urea-nitrogen14.70  "  = 87.5%2.20  "  = 61.7%
Uric acid-nitrogen 0.18  "  = 1.1%0.09  "  = 2.5%
Creatinin-nitrogen 0.58  "  = 3.6%0.60  "  =17.2%

Here we see, as would be expected, that on the high proteid diet, there was a large excretion of total nitrogen and of urea; while on the low proteid diet, nitrogen and urea were correspondingly diminished. The point to attract our attention, however, is the marked difference in the percentage of urea-nitrogen in the two cases; a difference which amounts to about 26 per cent. A similar difference is to be noted in the percentage of uric acid-nitrogen. Lastly, it is to be observed that in spite of the great difference in the extent of metabolism on the two days—an excretion of 16.8 grams of nitrogen, as contrasted with 3.6 grams—the amount of creatinin-nitrogen is essentially the same. Folin finds that these peculiarities in the percentage distribution of excreted nitrogen hold good in all cases where there is this wide divergence in the amount of proteid katabolized, and, further, that there is a gradual and regular transition from the one extreme to the other. He sees in these results evidence that there are in the body two forms of proteid katabolism, essentially independent and quite different. One kind is extremely variable in quantity, while the other tends to remain constant. The variable form has its own particular kind of waste products, of which urea is the chief. The constant katabolism, on the other hand, is largely represented by creatinin and to a lesser degree by uric acid. The more the total katabolism is reduced, the more prominent become creatinin and uric acid, products of the constant katabolism; while urea, as chief representative of the variable katabolism, becomes less conspicuous. Folin suggests the term endogenous or tissue metabolism for the constant variety, while the variable form he would name exogenous or intermediate metabolism.