The hydrogen-peroxide thus formed combines with carbonic oxide to form carbonic acid, which in turn is decomposed into the anhydride CO2, with regeneration of water, the latter being available for further action of the same order:
H2O2 + CO = CO(OH)2
2 CO(OH)2 = 2 CO2 + 2 H2O.
Indeed, as can be readily seen from the equations, this may be kept up indefinitely, a small amount of water, i.e., the go-between, the catalytic agent, sufficing to accomplish the transformation of almost any amount of carbon-monoxide. This, I think, furnishes an excellent illustration of the way in which catalytic agents, such as the proteolytic enzymes, may be supposed to act. It is truly contact action, but the agent is not purely passive; the enzyme combines with the substance undergoing proteolysis, and the resultant compound thus formed is enabled now to combine with water and undergo hydrolysis, something which could not be accomplished by the proteid and water alone, that is at body temperature. This new and more complex compound is naturally less stable and soon undergoes dissociation or cleavage with a splitting off of the original enzyme for one product, which is thus available for further action of the same order; while, as other products, we find the hydrated and otherwise altered substances coming from the proteid, and whose formation is the ultimate object of the whole process.
The parallelism between this hypothetical action of the proteolytic enzymes and the known reactions in the above combustion of carbonic oxide is certainly very close, and leaves little doubt that this explanation of enzyme action is, in a general way at least, correct. Thus the carbonic oxide, CO, brought in contact with pure, dry oxygen gas (apparently all that is necessary for its direct oxidation into carbonic acid, CO2), undergoes no change; the burning CO gas is at once extinguished. Evidently, something more is necessary in order to start the process of oxidation. So, too, in proteolysis; the process, as we shall see later on, is essentially one of hydration, but bring the proteid and the water, or acid-water, together and although all the conditions are apparently favorable for hydration there is, as you know, little or no change. But introduce the catalytic agent and immediately the reaction commences. In the case of the burning CO gas in contact with oxygen, the water acting as contact agent makes oxidation possible, enabling the main actors in the transformation to react upon each other. But, as we have seen, the contact agent is something more than a mere looker-on, it becomes for the time being an integral part of the molecule, undergoing change, combining with it and thus making possible the subsequent alterations characteristic of the specific transformation, in which, however, the regeneration of the contact agent is a prominent feature. So, too, with the proteolytic enzymes, pepsin and trypsin, they are the go-betweens, making possible the union of the proteids with water by combining with the proteid molecule and thus paving the way for both hydration and cleavage. In the cleavage of the complex molecule, we have the regeneration of the ferment as a prominent feature, and in proteolysis we understand that the regenerated ferment may act not only upon more of the original proteid, but likewise upon the primary products of its action, thus giving rise eventually to a row of more or less closely related cleavage products. Finally, we can conceive that the enzyme may gradually be affected by the process, that its regeneration may become less complete, and thus digestive power be eventually diminished.
Much more might be said in support of the above hypothesis. On the other hand, some objections might be raised against it, but I know of no more reasonable explanation of enzyme action than that here presented, or one which so well accords with all of the known facts concerning the conditions which modify proteolytic action.[48] Thus, the influence of heat, of the products of proteolysis, of acids, alkalies, and various organic and inorganic salts on the action of these digestive enzymes is such as lends favor to the above view rather than opposes it.
THE GENERAL NATURE OF PROTEIDS.
Proteids are confessedly among the most complex bodies the physiologist has to deal with, while at the same time they are perhaps the most important, not only in view of their wide-spread distribution through animal and vegetable tissues, but because of the prominent part they take in the nutrition of the body. The more our knowledge is broadened concerning these varied substances, the more we are impressed with their complexity, and at the same time with the necessity for a more accurate study of both their composition and constitution. Concerning the latter, full fruition of our hopes is probably in the distant future, but every step of advance in this direction adds greatly to our resources in the interpretation of the varied and complex changes characteristic of proteid metabolism. Every study of proteid decomposition adds something to our store of knowledge, and gives perhaps an added fact available for broadening our deductions.[49] Moreover, the composition and general reactions of the proteids may be investigated with full confidence of obtaining many useful results, which must necessarily be an aid in interpreting the changes accompanying digestive proteolysis.
Take, for example, the single question of peptonization by gastric digestion. What is the nature of the process? Is the proteid transformed into a soluble and diffusible peptone as a result of hydration and cleavage, or is it a transformation which results from a simple depolymerization of the proteid molecule, i.e., are we to consider albumin and peptone as isomeric bodies? These questions, on which physiologists seem loath to agree, can certainly be answered definitely; not, however, by arguments but by careful experimentation, in which the composition of the proteid undergoing digestion must be a necessary preliminary factor, and the composition of the resultant product, or products, a secondary factor of equal importance. Further, the question needs to be answered not with reference to one proteid merely, but with reference to every proteid capable of digestion by either gastric or pancreatic juice. When these questions have been fully answered in this manner, we shall have positive data to deal with, and our conclusions will rest upon a foundation of fact not easily set aside. This is one of the problems upon which I have been at work for some years, and although progress may in one sense be slow, yet it is sure and gives results of no uncertain character.
First, then, let us consider briefly the nature of the proteids whose proteolysis we may be interested in; remembering, however, that in so doing we can merely touch upon the points essential for our purpose. Allow me to say in parenthesis that there is being published in Moscow a work on proteids alone of five volumes, 900 pages each, which it is supposed will constitute an exhaustive treatise of the subject.[50]
If we attempt to classify all of the proteid bodies hitherto discovered and studied we are at once confronted with a problem of no small proportions. So varied are they in their reactions, solubilities, and behavior toward general reagents, so inclined to merge into each other by almost insensible gradations that it becomes an extremely difficult matter to make an arrangement that will satisfy all the requirements of the case. I have to suggest, however, the following classification, which is merely a modification of several existing ones, based primarily upon chemical composition, and solubility in the more common menstruums.