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:

In these various decomposition products there is apparent certain definite lines of resemblance, on which is based one or more suggestions regarding possible ways in which these chemical groups are linked, or bound together, in the proteid molecule. Thus, there is apparently present a complex or nucleus which may be indicated as

The proteid molecule is presumably built up of amino-acids variously joined together, this synthesis being accomplished, doubtless, by the condensation of different types of amino-acids, in which the first of the above groups represents the more common method of union. We may indeed conjecture that such methods of condensation take place in the human body, in the epithelial cells of the intestine, and in the tissues in general; and that by such methods, construction of proteid is accomplished out of the various fragments split off by digestion, etc. In a tentative way, the principle may be illustrated by the fusion of leucin and glutaminic acid,—following Hofmeister’s suggestion,—in which a still larger complex is formed:

In this way, step by step, the proteid molecule is built up, and naturally in katabolism the proteid breaks down along certain definite lines of cleavage, with formation of katabolic products containing those groups, or chemical nuclei, which characterize the different proteid molecules. For it is to be clearly understood that there are many different forms of proteid, perhaps superficially alike, but possessed of physiological individuality. This is well illustrated by the two primary proteoses formed in digestion. As will be recalled, there are at first two proteoses produced, protoproteose and heteroproteose. These are, superficially at least, not radically unlike; they possess essentially the same percentage composition, but when broken down by vigorous chemical methods they show a totally different make-up. In other words, at the very beginning of digestion there is a splitting up of the proteid into two parts, which have quite a different chemical structure, as is clearly indicated by the difference in the character and amount of the decomposition products yielded by hydrolytic cleavage. Thus, heteroalbumose as derived from blood-fibrin contains 39 per cent of its total nitrogen in basic form, i. e., in a form which goes over into the basic bodies, arginin, lysin, and histidin, etc. On the other hand, protoalbumose from the same source yields hardly 25 per cent of basic nitrogen. Further, heteroalbumose yields only a very small amount of tyrosin, while protoalbumose gives on decomposition a large amount of this substance. Again, heteroalbumose furnishes a large yield of leucin and glycocoll, while protoalbumose gives no glycocoll and only a little leucin. Obviously, these two proteoses have an inner structure quite divergent one from the other, and owing to this fact they must play a quite different rôle in metabolism.

Even greater differences in inner chemical structure are found among native proteids. By way of illustration, we may take egg-albumin, the casein of cow’s milk, gliadin of wheat, and the edestin of hemp seed. These are all typical proteids; they are all useful as food, but they are radically different in their inner chemical structure, as is clearly indicated by the following data,21 which show the percentage yield of the different amino-acids and ammonia:

These are not mere technical differences, but they represent divergences of structure which cannot help counting as material factors in nutritional processes. Especially noticeable is the large yield of glutaminic acid from wheat proteid, as contrasted with the proteid (casein) of animal origin. As a rule, glutaminic acid forms a larger proportion of the decomposition products of vegetable than of animal proteids. Similarly, arginin is present in much larger proportion in most vegetable proteids than in most animal proteids. While many other data more or less trustworthy might be added, these figures will suffice to emphasize the main point under discussion, viz., that individual proteids show marked variation in the amount of the several amino-acids which serve as corner-stones or nuclei in the building up of the molecule, and consequently they must yield correspondingly different katabolic products when serving the body as food.

Turning now to another phase of tissue metabolism, we may consider briefly the nucleoproteids and their characteristic decomposition products; bodies which are widely distributed as cleavage products formed in the disintegration of most cell protoplasm, and having special interest in nutrition because of their chemical relationship to that well-known substance, uric acid. Nucleoproteids of some type are found in all cells; consequently they are present in all tissues, in all glandular organs, and their widespread distribution constitutes evidence of their great physiological importance. Nucleoproteids are compound substances made up of some form of proteid and nucleic acid. By simple hydrolysis with dilute mineral acids they are broken down into proteid, phosphoric acid, and one or more bodies known as nuclein bases. Of these latter substances, there are four well-defined bodies, viz., adenin, hypoxanthin, guanin, and xanthin, which from their peculiar chemical constitution are known as “purin bases.” In the body, there is present in many cells a peculiar intracellular enzyme termed nuclease, which has the power of liberating these purin bases from their combination as a component part of tissue nucleoproteids, or of the contained nucleic acid. In autolysis or self-digestion of many glands, such as the spleen, thymus, etc., this chemical reaction is easily induced by action of the contained nuclease. Further, the liberated purin bases then undergo change because of the presence of certain deamidizing enzymes, and as a result guanin is transformed into xanthin, and adenin is converted into hypoxanthin. These ferments are true intracellular enzymes, and are termed respectively guanase and adenase. The real essence of the reaction they accomplish is clearly indicated by the following formulæ, which likewise show the chemical nature and relationship of the four substances:

These two enzymes are typical hydrolyzing enzymes, but it is to be noted that there is not only a taking on of water with a retention of the oxygen, but there is also a giving off of ammonia, by which the transformation is made possible. Adenin is known as an amino-purin and guanin as an amino-oxypurin, while hypoxanthin is an oxypurin and xanthin a dioxypurin. In other words, the two intracellular enzymes are able to transform the two amino-purins into the corresponding oxypurins; i. e., the enzymes are deamidizing ferments, liberating the NH₂ group of the adenin and guanin and thus forming two new compounds. These reactions, though more or less technical, are emphasized in this way not merely because they illustrate the action of intracellular enzymes in intermediary metabolism, thus affording a striking example of the gradual changes that take place in ordinary katabolic processes, but especially because they throw light upon the production of another substance common in body metabolism, viz., uric acid. It has long been known that nucleoproteids, nucleins, and other compounds containing these purin radicles, when taken as food, cause at once an increased output of uric acid, and it has been clearly recognized that in some way this latter substance, as a product of metabolism, must come from the transformation of nuclein bases. To-day, we understand that in many tissues, as in the liver, spleen, lungs, and muscle, there is present a peculiar oxidizing ferment, an oxidase, by the action of which hypoxanthin can be converted into xanthin, and the latter directly oxidized to uric acid. This conversion into uric acid is purely a process of oxidation, brought about by a typical intracellular oxidase, known specifically as “xanthin oxidase,” the reaction involved being as follows:

From these several reactions, it is clear how various intracellular enzymes working one after the other are able gradually to evolve uric acid from tissue nucleoproteids. Further, it is to be noted that there is another tissue oxidase—contained principally in the kidneys, muscle, and liver—which has the power of oxidizing and thus destroying uric acid, with formation, among other substances, of urea. Remembering that urea has the following chemical constitution

it is easy to see, by comparison of the formulæ, how uric acid might easily yield two molecules of urea through simple oxidation. In this way, excess of uric acid produced in the body can be converted into urea, and in this harmless form be excreted from the system.

Finally, reference should be made here to several other products of tissue metabolism, products of the breaking down of proteid matter in the body, since they are liable to prove of interest to us in other connections. Thus creatin, abundant in the muscle and other places; the related substance creatinin, present in the urine; methyl guanidin, a decomposition product of creatin; and urea, all call for a word of description. The chemical relationship of these bodies is clearly indicated by the following formulæ:

Creatinin is chemically the anhydride of creatin, i. e., it can be formed from creatin by the simple extraction of one molecule of water, H₂O. Creatin, by hydrolytic cleavage, will break down into one molecule of urea and one molecule of sarcosin or methyl glycocoll, as shown in the following equation:

Methyl guanidin is a decomposition product of creatin, while guanidin, as can be seen from the formula, is like urea, excepting that the group NH replaces the oxygen of urea. These simple statements will suffice for our present purpose, viz., to indicate the more or less close chemical relationships existing between many of these nitrogenous decomposition products resulting from proteid katabolism; also to suggest how by slight chemical alteration one decomposition product may be resolved into another related substance in the processes of katabolism. Our conception of the processes involved in proteid katabolism is that of a series of progressive chemical decompositions, in which intracellular enzymes play the all-important part. The intermediary products formed are definite bodies because of the specific nature of the active enzymes, and, secondly, because of the chemical nature of the substances acted upon. In other words, oxidation in the animal body takes the shape of a series of well-defined chemical reactions, in which chemical constitution and specific enzyme action are the predetermining cause. In the absence of the particular chemical groups, the oxidase is unable to bring about oxidation, or, given the proper compound or mother substance in the absence of the specific oxidase, there is no oxidation. Hence, oxidation in the animal body is not the result of simple combustion, but, on the contrary, it consists of a series of orderly chemical processes, each one of which is presided over by an intracellular enzyme, specific in its nature, in that it is capable of acting only upon substances having a certain definite constitution, and leading invariably to a certain definite result. The processes which years ago were considered as due to the peculiar vital properties of the tissue cells, and which were supposed to be entirely dependent upon their morphological and functional integrity, are now seen to be due primarily to a great variety of enzymes, manufactured indeed by the living cells, but capable of manifesting their activity even when free from the influence of the living protoplasm. The varied processes of tissue katabolism are the result of orderly and progressive chemical changes, in which cleavage, hydrolysis, reduction, oxidation, deamidization, etc., alternate with each other under the influence of specific enzymes, where chemical constitution and the structural make-up of the various molecules are determining factors in the changes produced.