R. H. Chittenden

“ Absorption of the products of digestion tends to increase the activity of the secreting cells, but we have no tangible proof that any particular kinds of food are directly peptogenous, i.e., that they lead to a storing up in the gastric cells, for example, of pepsinogen, although it may be that the so-called peptogenous foods give rise to a more active conversion of pepsinogen into pepsin.23 As already stated, the zymogen is manufactured directly from the cell-protoplasm, and the constructive power is certainly not directly controlled by the character of the food ingested. ”

“ Loew considered the ferment to be a true peptone, but in view of our present knowledge regarding the albumoses, I think we are justified in assuming it to be an albumose-like body rather than a true peptone. At the same time it may be well to again emphasize the fact that our only “means of determining the presence of an enzyme is that of ascertaining the change which it is able to bring about in other substances, and since the activity of the enzymes is extra­ordinarily great, a minute trace suffices to produce a marked effect. ”

“ We know without a shadow of doubt that all of the bodies enumerated as products of pancreatic digestion are the results of trypsin-proteolysis, and not the products of putrefactive changes. Bacteria, it is true, are able to produce many like products, and in the living intestinal tract exercise an important influence, especially in the breaking down of resistant forms of proteid matter, and in the decomposition of surplus material which has escaped the pancreatic ferment. ”

“ In pepsin-proteolysis we have to deal, in my opinion, with a series of progressive hydrolytic changes in which peptones are the final products of the transformation. Commencing with the formation of acid-albumin or syntonin, hydrolysis and cleavage proceed hand in hand, under the guiding influence of the proteolytic enzyme, and each onward step in the process is marked by the appearance of a new body corresponding to the extent of the hydrolysis ”

“ In considering the general phenomena of proteolysis by trypsin, one is especially impressed by the large and rapid formation of peptone which almost invariably results from the action of a moderately strong solution of the ferment, on nearly every form of proteid matter. To be sure, primary products are first formed, but these are quickly converted into peptone, and a little experience in studying the action of pepsin and trypsin soon reveals the fact that the latter is especially a peptone-forming ferment. ”

“ It is very evident from what has been said that all forms of proteid matter, i.e., all the members of the three main groups spoken of in our classification of the proteids, excepting only nuclein, reticulin, and the keratins, are capable of undergoing proteolysis with pepsin-hydrochloric acid. Further, in every case the main products of the transformation are proteoses; viz., albumoses, caseoses, gelatoses, vitelloses, myosinoses, etc., according to the nature of the proteid undergoing proteolysis; true peptones being formed in less abundance. ”

“ Thus, when it was suggested that ammonia, NH3, might be formed under the influence of trypsin, it was not considered at all improbable, for in the hydrolytic decomposition of proteids by boiling dilute acid, as well as by baryta water, it had long been known as a prominent product. Obviously, in trypsin-proteolysis, the one thing to be guarded against in proving the formation of ammonia is the contaminating influence of bacteria. ”

“ At the same time, as already stated, it seems more than probable that some formation of these amido-acids always occurs in the intestine, and that these bodies have some specific part to play in the normal processes of metabolism going on in the body. The more one studies the processes of nutrition in general, the more one is impressed with the view that there is a purpose in everything, and that the formation of even such bodies as leucin and tyrosin may be connected with hidden processes, the key to which has not yet been found. ”

“ This is to be greatly deprecated, since our understanding of the nature of proteolysis, of the mode of action of the enzymes or ferments involved, and of the relationships of the products formed, is dependent mainly upon an accurate determination of the exact changes in chemical composition which accompany each step in the proteolytic process. How otherwise can we hope to attain a proper appreciation of the real points of difference between bodies so closely related as those composing the large group of proteids and albuminoids? ”

“ In fact, there seems to be a tendency on the part of some who are more or less familiar with the advances made in our knowledge of the products of pepsin-proteolysis to question the existence of these different bodies, or to show at least a spirit of indifference toward these recent facts which have been gradually accumulated, and I may say accumulated at the expense of considerable labor. ”

“ But large quantities of sugar in the blood are certainly inimical to the well-being of the organism, and we find in the liver a tendency for the sugar to undergo a transformation, i. e., a retrogression into glycogen, either through simple dehydration or otherwise. Further, with reference to the possible conversion of proteoses into peptone by the substance of the intestine, we have a perfectly analogous case in the behavior of the intestinal mucous membrane toward maltose, the final product of amylolytic action. ”

“ In the living stomach, on the other hand, where the secretion of acid is progressing with ever-increasing rapidity, it is easy to see that the process of proteolysis would naturally be much more rapid. ”

“ These two experiments thus give striking proof that free acid is not absolutely essential for pepsin-proteolysis. Digestion is, to be sure, more rapid and complete when free hydrochloric acid is present, but proteolysis is still possible, and even vigorous, when there is a marked deficiency of free acid. Further, as we have seen, proteolysis may proceed to a certain extent even though the amount of acid available is not sufficient to combine with more than half the proteid matter present. ”

“ Peptones are truly formed, and many times in large amount, but never under any circumstances have I been able to effect a complete transformation of any proteid into true peptone by pepsin-proteolysis; there is always found a certain amount of proteoses more or less resistant to the further action of the ferment. Obviously, the nature and proportion of the individual products formed in any digestive experiment are dependent greatly upon the attendant conditions ”

“ Gastric digestion is to be considered rather as a preliminary step in proteolysis, preparatory to the more profound changes characteristic of pancreatic digestion, in which the ferment trypsin is the important factor. We can thus see how, as in the case of Czerny’s dogs, an animal may be perfectly nourished without a stomach, digestive proteolysis being carried on solely by the pancreatic fluid. ”

“ These facts at once raise the question whether the products of proteolysis may not have a stronger affinity for acid than the native proteids; an affinity so strong that they may be able to withdraw acid from the acid-albumin first formed. One of our conceptions regarding pepsin-proteolysis is that acid is necessary for every step in the proteolytic process. ”

“ Thus, it is a significant fact, as Pohl himself reports, that wheat-bread, with its fairly large amount of proteid matter, and which is fully capable of nourishing the animal body, fails to exert any influence on the number of leucocytes in the blood. Yet we know that the gluten and other proteids of wheat-flour are converted by digestive proteolysis into proteoses and peptones, with the same general properties as like products of animal origin. ”

“ Further, the amount of solids in the lymph, especially of proteids, is considerably increased. From these and other facts, Heidenhain is led to the view that the formation of lymph is a true secretion from the blood-vessels. Shore finds that when small amounts of peptone are slowly injected into the blood, there is generally only a slight acceleration in the flow of lymph, but the clotting power of the lymph is affected in a remarkable manner. Thus, about twenty minutes after the commencement of the injection the lymph loses entirely its power of coagulating. ”

“ 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. ”

“ The primary object of both gastric and pancreatic proteolysis is to render the proteid foods more easily available for the needs of the economy, viz., to aid in their absorption and consequent distribution to the master tissues and organs of the body. ”

“ If there is, that gastric juice may be just as normal as the one containing free mineral acid, and yet, according to our present tendencies, we should be inclined to call the juice containing no free acid abnormal, although there may be sufficient combined acid present to meet all the requirements for digestion. ”

“ Another factor of great moment in determining the activity of these two enzymes is temperature. That which is most favorable for their action is 38° to 40° C., and any marked deviation from this temperature is attended by an immediate effect upon the proteolysis. Exposure to a low temperature simply retards proteolytic action, doubtless in the same manner that cold checks or retards other chemical changes. There is no destruction of the ferment, even on exposure to extreme cold, the enzyme being simply inactive for the time being. ”

“ In general properties and reactions, pepsin and trypsin may be closely related; both are products of the katabolic action of specific protoplasmic cells, but the inner nature or structure of the two must be quite different. Pepsin, as we have seen, is powerless to produce any change in proteid bodies unless acids are present to lend their aid. Furthermore, pepsin is limited in its action to the production of proteoses and peptones, while trypsin gives rise to a series of hydrolytic cleavages which result in the ultimate formation of comparatively simple bodies. ”

“ Leucocytes, then, can play no direct part in the absorption of the products of proteolysis from the intestine; the lymph is normally free from both proteoses and peptones, and the leucocytes plainly have no power to transform these bodies into other forms. They can only utilize the proteid material elaborated from the products of proteolysis by other agencies. ”