Proteolysis

“ We have to deal not only with a number of bodies superficially unlike, as the primary and secondary proteoses and peptones, but these bodies may show marked variations in structure dependent upon the exact conditions attending their formation.
Evidently, the complexities attending digestive proteolysis are connected primarily with the complex nature of the proteids themselves, while proteolysis, as a process, is made possible through the natural tendency of the proteids to undergo hydration and cleavage. ”

“ Still, there are other differences between natural digestion and artificial proteolysis than those connected with the possible absorption of the more diffusible products of digestion. Thus, in the living stomach there is an ever-increasing secretion of hydrochloric acid, and perhaps also of pepsin, more or less proportional to the extent of proteolysis. On this point Brandl’s experiments again give us some light. Thus, it was found that the introduction of an aqueous solution of peptone into the empty stomach led to the secretion of an acid fluid containing on an average 0.24 per cent. ”

“ It is true that, with the limitations of our present knowledge, it is difficult to see why if digestive proteolysis has for its sole object the conversion of the proteid foods into forms suitable for absorption there should be any considerable breaking down of proteid beyond the proteose or peptone stage, since the latter bodies would seem to be most easily adaptable for transformation into the proteids of blood, lymph and tissue. ”

“ The proteids, for example, have a natural tendency to undergo hydration; thus, simple boiling with dilute acid or exposure to the action of superheated water alone,45 will produce many if not all of the products formed in natural digestive proteolysis. To be sure, they are not formed as readily as in artificial or natural digestion, and there may be some minor points of difference, but still proteolysis can be imitated in this manner. ”

“ 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 ordinary proteolytic action, both in the stomach and intestine, it is very apparent that the primary products of proteolysis, the proteoses and peptones, are the chief products formed, and that under normal circumstances the greater portion of the proteid food finds its way from the alimentary canal into the blood, after transformation into one or more of these two classes of products. At the same time, it must be borne in mind that even the acid-albumin formed by pepsin-hydrochloric acid may be absorbed without undergoing further change. ”

“ Another point to be emphasized just here is that any chemical substance, such as a metallic salt, having a specific action upon proteid matter, will almost invariably interfere more or less with the proteolytic action of these enzymes, both through a direct action upon the soluble ferment itself, and also through an indirect action in modifying or inhibiting the digestibility of the proteid exposed to proteolysis. ”

“ At first there is a marked and rapid progression; the proteid undergoing proteolysis is rapidly dissolved, and both proteoses and peptones may be detected in abundance. But if we continue to watch the changing relations of primary and secondary proteoses and peptones, we find that progression soon ceases to be rapid, and eventually travels onward at a snail’s pace. Thus, in one experiment with coagulated egg-albumin, there was found at the end of forty-eight hours’ digestion with pepsin-hydrochloric acid, only thirty-seven per cent. ”

“ In pancreatic digestion, proteids are exposed to the action of an enzyme of much greater power than pepsin, one endowed with a far greater range of activity, and consequently proteolysis as it occurs in the small intestine becomes a broader and more complicated process. As you well know, the ferment trypsin manifests its power not only in a more rapid transformation of insoluble proteids into soluble and diffusible products, but there is a diversity in the character of the many products formed which testifies to the profound alterations this ferment is capable of producing. ”

“ 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. ”

“ 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? ”

“ Further, the recent experiments of Huber200 have given us quantitative data on the rate of absorption of fluid egg-albumin when introduced into the large intestine in the form of a clyster, showing that even fairly large amounts of a natural proteid may be absorbed without undergoing proteolysis if mixed with a neutral salt, like sodium chloride. To be sure, the rate of absorption is greatly increased when the albumin has been peptonized, but still absorption of the native proteid is possible without the agency of proteolytic enzymes. ”

“ In the deutero­proteoses, however, the loss of carbon is very marked. The percentage loss, to be sure, varies with the different proteids, doubtless dependent in part upon the nature of the proteid itself, and also, I think, upon the strength of the proteolytic agent employed and the duration of the proteolysis. It is to be further noticed that peptones, whenever analyzed, show a still further loss of carbon and also a marked loss of sulphur. In nitrogen there is no constant difference. ”

“ This experiment is almost a counterpart of one reported by Neumeister, and like his, testifies to the probability that the peptones formed in the alimentary tract, as a result of proteolysis, undergo retrogression through the agency of the epithelial cells of the intestinal walls during their absorption. I have tried similar experiments with deutero­proteose, notably with deuterocaseose, and have obtained corresponding results. The same method may be employed as that already outlined, although of course the deuterocaseose is in great part precipitated by saturation with ammonium sulphate. ”

“ Just as the so-called secreting cells of the tubuli uriniferi may lose for a time their power to pick out from the blood material destined for the urine, being clogged or exhausted by continued effort, so the epithelial cells of the intestine, which play such an important part in the absorption of proteid matters from the alimentary tract, may, in the presence of an excess of proteid matter, become temporarily exhausted, and, refusing passage to the proteoses and peptone formed by proteolysis, render possible further hydrolytic cleavage into leucin, tyrosin, lysatin, etc. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ Drechsel estimates that about one-ninth of the urea daily excreted may come from the direct decomposition of lysatin, the latter obviously having its origin in trypsin-proteolysis.
Another product of trypsin-proteolysis which has long been recognized, although its real nature has not been known, is tryptophan or proteino­chromogen. This body is not only a product of the pancreatic digestion of proteids, but it is also formed whenever native proteids are broken down through any influence whatever, the substance coming presumably from the hemi-moiety of the molecule. ”

“ But even admitting this, we lack positive proof of any direct transformation of proteoses and peptones into the organized material of the white blood-corpuscles, for it may be that the above products are first transformed through other agencies into serum-albumin, or other like proteids. There are, indeed, many facts which are plainly opposed to any marked absorption and transformation of peptones by the leucocytes of the intestinal mucous membrane. ”

“ This body can be reconverted into heteroproteose, in part at least, by solution in dilute acid, or alkali, and reprecipi­tation by neutralization.
As a class, the proteoses are characterized by far readier solubility in water than native proteids, by a far greater degree of diffusibility, by non-coagulability by heat and by alcohol, although precipitable by the latter agent. Further, nearly all proteose precipitates are exceedingly sensitive toward heat, tending to dissolve as the fluid is warmed and reappearing as the solution cools. ”