If Liebig’s theory is correct, that the proteids of the body are decomposed only as the result or the accompaniment of muscle work, and the proteids of the food are used up only as they take the place of the organized proteid so metabolized, it follows that with a like degree of muscular activity a given body will always decompose the same amount of proteid. If excess of proteid food is taken, the surplus will be stored in the tissues, or, in other words, the excretion of nitrogen will not be influenced by the amount of proteid consumed in the food. This was the line of argument made use of by various physiologists[18] who were disposed to criticise Liebig’s view, and quite naturally the question was soon made the subject of many experiments. It will suffice here merely to say that many concordant results were obtained, showing that an abundance of proteid food leads to an increase in the excretion of nitrogen, muscle activity remaining at a constant level. Hence, as Voit states, some other ground than muscle work must be sought as the true cause of proteid katabolism. Consequently, we find this hypothesis of Liebig replaced by the theory of “luxus consumption,” in which it is maintained that while whatever proteid is used up by the work of the muscle must be made good from the proteid of the food, any excess of proteid absorbed from the intestinal canal is to be considered as “luxus,” and like the non-nitrogenous foods may be burned up in the blood, by the oxygen therein, without being previously organized. Hence, we see suggested two causes for the decomposition of proteid in the body, viz., the work of the muscle and the oxygen of the blood. Further, as stated by C Voit,[19] the nitrogen excretion of the hungry or fasting animal affords, according to these views, a measure of the extent to which tissue proteid must be broken down in the maintenance of life, and of the amount of proteid food necessary to be consumed in order to make good the loss; viz., the minimum proteid requirement. Again, since any excess of proteid food beyond this minimal requirement, according to the theory, is destined to be burned up in the blood, or elsewhere, to furnish heat the same as non-nitrogenous foods, it follows that the excess of proteid food can be replaced by non-nitrogenous aliment.
Oxidation, however, is the keynote in any explanation of the processes of metabolism, whether nitrogenous or non-nitrogenous matter is involved. Both alike undergo oxidation, but it is not simple oxidation or combustion that we have to deal with. In the time of Lavoisier, as already stated, it was thought that oxygen alone was the cause of the decomposition going on in the body, but simply increasing the intake of air or oxygen, as in quickened breathing or deeper inspiration, does not increase correspondingly the rate of oxidation. In other words, it is not a direct combination of oxygen with the carbon and hydrogen of the foodstuffs, or tissue elements, that takes place in the body, but rather a gradual, progressive decomposition of complex organic compounds into simpler products; made possible, however, by the agency of the oxygen carried from the lungs by the circulating blood. It was demonstrated years ago that animals breathing pure oxygen do not consume any more of the gas than when breathing ordinary air, and likewise no more carbon dioxide is produced in the one case than in the other. Fifty years ago, Liebig and other physiologists showed that frogs’ muscle placed in an atmosphere free of oxygen could be made to contract or do work for some considerable time, and with liberation of heat. This fact implies a breaking down of muscle substance into simpler bodies, but there is here no free oxygen to act as the inciting cause; indeed, what actually occurs is a cleavage or splitting up of substances in the muscle tissue, but at the expense of oxygen in some form of combination in the muscle. This oxygen must have been taken from the blood at some previous time and stored in the tissue for future use. Again, as C Voit has expressed it, if oxygen were really the immediate cause of the decompositions taking place in the organism, we should expect combustion to occur in harmony with the well-known relationship of the three classes of organic foodstuffs to oxygen. In other words, fats would undergo combustion most readily, carbohydrates next, and lastly the nitrogenous or albuminous compounds. In reality, however, proteid matter is decomposed in largest quantity; a generous addition of proteid food is always accompanied by an increased consumption of oxygen. Yet oxygen is not the inciting cause of the proteid decomposition, as is seen from the fact that in muscle work, where the intake of oxygen is greatly increased, there is no noticeable change in the amount of proteid material broken down. Plainly, in the body we have to deal not with a direct oxidation of the complex compounds of the tissues or of the food, but rather with a gradual cleavage of these higher compounds into simpler substances, these latter undergoing progressively a still further breaking down with intake of oxygen. To repeat, oxygen is not the cause of the decompositions within the body, but the extent of the breaking down of the tissue or food material is the determining factor in the amount of oxygen taken on and used up. The products of decomposition contain more oxygen than the original substances undergoing the breaking down process, which means that oxygen is taken from the blood and used in the physiological combustion that is going on. It is not, however, strictly a combustion process; it is more complicated and more gradual than ordinary combustion, involving first of all a series of what may be termed oxidative cleavages, in which large molecules are gradually, step by step, broken down into simpler molecules, and these latter then oxidized to still simpler forms. Hence, we find the oxidative changes preceded by a variety of alterations in which oxygen may take no part whatever; such as hydrolytic cleavage, where the elements of water are taken on as a necessary step in the cleavage process; dissociation of a simple sort, as when a large molecule breaks up directly into smaller molecules, etc.
These statements by no means detract from the importance of oxygen in the katabolic processes of the body, but it is physiological oxidation that we have to do with, and not simple combustion. Oxygen is not the direct cause of the transformations taking place in the body. As one looks over the history of progress in our knowledge of nutrition from the time of Lavoisier to the present, it is easy to note the gradual change of view regarding oxidation in the living organism. Step by step, it has been demonstrated that there are many factors involved in this breaking down of complex substances; that while oxygen is an ever present requirement, there are other equally important factors to be taken into account. The contrast between the older views and those now current is clearly shown by the difference in attitude regarding the place in the body where oxidation occurs. Thus, in the earlier days, when the view was gradually gaining ground that nutritional changes were mainly the result of oxidation, and that the oxygen drawn into the lungs in inspiration was a primary factor, then, as we have seen, the lungs were considered as the laboratory where the transformation takes place. This view, however, was soon exploded, and next we find the blood, the lymph, and other fluids, but especially the blood, looked on as the locality where oxidation occurs. This was indeed quite a natural view to hold, since the blood is the carrier of oxygen, but we now know, in harmony with the fact that the breaking down of complex food material is a complicated process, involving various kinds of chemical change, that these katabolic processes are not located in any one place, but occur all over the body wherever there are active tissues. As has been previously stated, the human body is a “nation” of cells, all of which are more or less active, and it is in these miniature laboratories mainly that oxidation and all the other nutritional changes coincident to life take place. Muscle tissue and nerve tissue, the large secreting glands, such as the liver, stomach, and pancreas, all are the seat of oxidative and other changes which we class under the broad term of nutritional. To these cells, therefore, we must look for an explanation of the causes of oxidation, and the other transformations of a kindred nature that take place in the body.
In our brief survey of digestion, and of the methods there followed for the proper utilization of the organic foodstuffs, it was seen that the unorganized ferments or enzymes are the active agents in accomplishing the breaking down of proteids, and the less profound alteration of fats and carbohydrates. Is it not possible that the tissues of the body are likewise supplied with enzymes of various types, and that upon these powerful agents rests the responsibility for the different kinds of decomposition, oxidation and other changes, that take place in the body? Some years ago much interest was aroused by the observation that certain glands in the body, if simply warmed at body temperature with water, in the presence of some germicidal agent sufficient to prevent putrefactive changes, underwent what is now termed autodigestion, i. e., a process of self-digestion, with formation of various products, notably such as would naturally result from the breaking down of proteid material by ordinary proteolytic enzymes. This would seem to imply the presence in the glands of a proteid-splitting enzyme, the products formed being proteoses, peptones, amino-acids, etc., just such products as result from the action of trypsin. To-day, we know that practically all tissues and organs can, under suitable conditions, undergo autolysis, and in many instances the enzymes themselves can be separated from the tissues by appropriate treatment. Liver, muscle, lymph glands, spleen, kidneys, lungs, thymus, etc., all contain what are very appropriately called intracellular enzymes. These enzymes are of various kinds. Especially conspicuous are the hydrolytic, proteid-splitting enzymes, which behave in a manner quite similar to, if not identical with, that of the digestive enzymes of the gastro-intestinal tract, i. e., pepsin, trypsin, and erepsin. Further, there are other hydrolytic cleavages taking place in tissue cells, such as the cleavage of fats, due as we now know to intracellular enzymes of the lipase type, and by which neutral fats are split apart into glycerin and fatty acid. Again, there are in many organs intracellular enzymes which act upon the complex nucleoproteids of the tissue, causing them to break apart into proteid and nucleic acid, the latter being further broken down by other enzymes with liberation of the contained nuclein or purin bases. Many other chemical reactions are brought about by specific enzymes of various kinds, present in the cells of particular glandular organs. Thus, intracellular enzymes have been found, as in the liver, which are able to transform amino-acids into amides, and still others capable of splitting up amides.
Equally important, and even more suggestive, are the data which have been collected recently regarding oxidative processes in the tissues of the body. Specific ferments, known as oxidases, are found widely distributed in many organs and tissues, and it is difficult to escape the conclusion that as intracellular enzymes they have an important part to play in some, at least, of the transformations characteristic of tissue katabolism.[20] As a single example, mention may be made of aldehydase, which accomplishes the oxidation of substances having the structure of aldehydes into corresponding acids. Ferments or enzymes of this class are found in the liver, spleen, salivary glands, lungs, brain, kidneys, etc., and they may well be considered as important agents in the chemical transformations going on in the tissues of the body. It would take us too far afield to enter into a detailed consideration of these intracellular enzymes; it must suffice to emphasize the general fact that in all the tissues and organs of the body there are present a large number of enzymes of different types, endowed with different lines of activity, and consequently capable of accomplishing a great variety of results in metabolism. Oxidation may still be a dominant feature in nutrition, oxidative changes may characterize more or less every tissue and organ in the body, but the processes are subtle and are not to be defined in harmony with simple chemical or physical laws. The living cell, with its intracellular enzymes, is the guiding and controlling power by which the processes of katabolism are regulated in harmony with the needs of the body. Complex organic matter is broken down step by step in the various tissues, with gradual liberation of the contained energy; processes of hydrolytic cleavage alternate with processes of oxidation, the molecules acted upon growing smaller with each downward step, until at last the final end-products are reached, viz., carbon dioxide, water, and urea, which the body eliminates through various channels as true physiological waste-products.
It will be advisable for us to consider briefly some of these intermediary products of tissue metabolism, since in any discussion of nutritive changes it is quite essential to have some understanding of the chemical relationship existing between the various products which result from the breaking down of proteid and other materials in tissue katabolism. This is especially true of proteid material, since in the gradual disintegration of this substance in tissue metabolism many intermediary bodies are formed, which undoubtedly exercise some physiological influence prior to their transformation into simpler bodies, with ultimate formation of the final product, urea. As has been pointed out so many times, the proteid foods are peculiar in that they alone contain the necessary nitrogen, and in the peculiar form able to meet the physiological requirements of the body. Variations in the proteid intake are of necessity accompanied by variations in the formation of nitrogenous intermediary products, and both quality and quantity of these substances must be given due attention in any study of nutrition. Further, it is only by an understanding of the general or ground structure of proteids that we can hope to attain knowledge of the processes going on in the different tissues and organs in connection with metabolism, while a true appreciation of the chemical peculiarities of the individual proteids will help to explain the different nutritional value of vegetable as contrasted with animal proteids.
Our understanding of the chemical structure of any organic substance is based primarily upon a study of the decomposition products which result from its breaking down, under the influence of various chemical agencies. Simple proteid substances when acted upon by pancreatic juice reinforced by the enzyme erepsin, or when boiled with dilute acids, undergo hydrolytic cleavage with ultimate formation of a large number of relatively simple bodies, mostly amino-acids, the chemical structure of which throws some light upon the nature of the proteid. Thus, in the pancreatic digestion of proteid in the intestine we may adopt the following scheme as showing in a general way the progressive transformation that occurs, understanding at the same time that like transformations may be accomplished by corresponding intracellular enzymes in the tissues and organs of the body; and further, that by the long-continued action of hydrolytic agents there is a complete breaking down into amino-acids and other simple products.
Native proteid, Protoproteose, Deuteroproteose, Heteroproteose, Primary proteoses, Secondary proteoses, Peptone, Amino-acids
Among these end-products, or amino-acids, are leucin, tyrosin, aspartic acid, glutaminic acid, glycocoll, arginin, lysin, histidin, and likewise the peculiar aromatic body tryptophan. The chemical make-up of these substances may be indicated by the following structural formulæ, which, if even only partially understood, will suggest to the non-chemical mind some idea of close chemical relationship: