ABSORPTION OF THE MAIN PRODUCTS OF PROTEOLYSIS.
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. The view once held, that the rate of absorption from the alimentary tract stands in close relation to the diffusibility of the products formed, and that non-diffusible substances are incapable of absorption, is no longer tenable. Absorption from the intestine is to be considered rather as a process involving the vital activity of the epithelial cells of the intestinal mucous membrane, where chemical affinities and other like factors play an important part in determining the rate and order of transference through the intestinal walls into the blood and lymph. Thus, we have abundant evidence that native proteids which have not undergone proteolysis may be absorbed from the intestine, at least to a certain extent, provided they have been dissolved; i. e., converted into acid-albumin, or alkali-albuminate, by the gastric or pancreatic juice. We have a practical demonstration of this possibility in the early experiments of Voit and Bauer,[199] as well as in many later ones that need not be mentioned here. Further, the recent experiments of Huber[200] 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. When, however, large amounts of egg-albumin are introduced into the intestine, albuminuria may result, as you very well know.
Moreover, it is well known that the proteids of muscle-tissue, in the form of syntonin, may be absorbed from the large intestine without undergoing further hydration. When introduced into the rectum of a hungry dog, the excretion of urea may be at once increased and the animal brought into a condition of nitrogenous equilibrium; absorption taking place from a portion of the large intestine, where proteolysis is never known to occur.[201]
Again, Neumeister[202] has shown that the direct introduction of syntonin, alkali-albuminate, crystalline phytovitellin, as well as pure serum-albumin, into the blood of the jugular vein is not attended with the appearance of albumin in the urine. On the contrary, the proteid matter so introduced appears to be assimilated and utilized for the needs of the organism. Evidently, then, these substances are not to be considered as foreign bodies, for if so the kidneys would undoubtedly make some effort to remove them from the circulation. It is to be noted, however, that all native proteids are not assimilated in this manner, as casein,[203] gelatin,[204] and especially egg-albumin. Thus, J. C. Lehman,[205] working under Kühne’s direction, observed that the injection of a carefully filtered solution of egg-albumin into the veins of a dog was always accompanied by albuminuria, while similar injections of Lieberkühn’s sodium albuminate, or of syntonin from frog’s muscle, failed to show any such result.
While these observations tend to show that some native proteids may be absorbed from the alimentary tract without previously undergoing proteolysis, it is not to be understood that any considerable quantity is so absorbed under normal circumstances. Doubtless, when small amounts of proteid food are taken, its denaturalization by the primary action of the gastric or pancreatic juice, viz., its conversion into syntonin or alkali-albuminate, may be sufficient to insure its partial absorption, but digestive proteolysis is unquestionably a necessary preliminary to any general absorption, and there can be no manner of doubt that the greater portion of the proteid food is absorbed as proteoses and peptone. Peptones, as we have seen, are possessed of a higher endosmotic equivalent than the proteoses, but we need to keep continually in mind the possibility that the selective power of the epithelial cells of the intestinal mucosa may lead to as rapid transference of the proteoses as of the more diffusible peptones. It is not to be understood by this, however, that diffusibility is of no consequence in determining the rate of absorption. Surely, everything else being equal, the more diffusible the substance the more rapid will be its passage from the intestine into the blood-current. The more the process of absorption is studied, however, the more clearly do we see its dependence upon the functional power of the living epithelial cells, a fact which plainly emphasizes the physiological nature of the process.
Further, as already stated, absorption of proteid food-stuffs, or their products, from the alimentary tract, is, under ordinary circumstances at least, limited to the intestine; from the stomach there is comparatively little absorbed, and if necessary we might advance this fact as an important argument against the theory of general absorption of proteids in the form of acid-albumin. Even such indifferent fluids as water, or physiological salt solution, are absorbed with extreme slowness from the stomach;[206] this organ showing very little ability to take up water even when the blood-vessels are dilated, as after the ingestion of food.
This brings us to a very important point in connection with the utilization by the system of the ordinary products of proteolysis. The latter, as we have seen, are mainly proteoses and peptones, and yet all the evidence points clearly to the fact that these substances are never present, at least in any quantity, in the blood or lymph, even when digestive proteolysis is at its height. Further, the very nature of the proteoses and peptones, their marked physiological action when they are introduced directly into the circulating blood, their rapid excretion, either as proteoses or peptones, by the kidneys when so introduced,[207] all indicate that they are foreign substances, totally out of their natural environment when introduced into the blood-current. And yet we very well know that proteoses especially are possessed of high nutritive qualities; they are abundantly able to support animal life. Thus, Politzer[208] found by feeding experiments with heteroalbumose, dysalbumose, and protoalbumose, that these bodies taken into the stomach have the same nutritive value as meat. Various feeding experiments with proteoses from different sources, carried out in my laboratory on young dogs, have shown conclusively that for short periods of time, at least, these hydrolytic cleavage products are fully as capable of sustaining the nitrogenous equilibrium of the body as the proteids from which they are derived. In fact, the results obtained favor the view that the proteoses, weight for weight, possess a higher nutritive value than fresh beef.[209] It may be questionable, however, whether such a result would follow in experiments conducted over longer periods of time, but of this we may be certain, that the proteoses formed in the alimentary tract can be absorbed and utilized by the system without their exerting any toxic action whatever.
Consequently, we are forced to the conclusion that these primary products of proteolysis, so important in the nutrition of the animal body, must undergo some change during the process of absorption, by which they are converted into new bodies, less toxic in their nature, and better adapted for the direct nutritional needs of the organism. The same statement applies likewise to peptones.
The fact that peptones are not discoverable in the blood and lymph, even during or after active digestion, was practically ascertained years ago by such well-known workers as Maly, Adamkiewicz, and others. The natural supposition following this observation was that the products of proteolysis underwent some change in the hepatic cells; but this view was soon shown to be untenable by examination of the portal blood, which was found to be as free from peptone as the blood of the hepatic vein. Neumeister,[210] using the more modern methods of work and with the wider knowledge gained during these latter years, has shown conclusively that proteoses and peptones are never present in the blood, even when these substances are contained in the intestine in fairly large amounts. I can corroborate these statements from the results of my own experiments in this direction. Thus, I have taken a dog in full digestion, fed with an abundance of meat, and collecting the blood from the carotid artery have made a careful examination for peptone, by the following method: The blood was allowed to flow directly into a dilute solution of ammonium sulphate, sufficiently strong to prevent coagulation, and then shaken with ether to rupture the red blood-corpuscles. The solution, freed from ether, was next saturated with crystals of ammonium sulphate, by which the proteid matter was completely precipitated. The clear filtrate was then concentrated somewhat, the excess of the ammonium salt removed by filtration, and the filtrate carefully tested for peptone by addition of a large volume of a saturated solution of potassium hydroxide and a few drops of a dilute solution of cupric sulphate. The test was wholly negative, although the intestine of the animal showed the presence of both peptone and proteoses. This result, as I have said, is simply confirmatory of work done by others in this direction, notably Neumeister, and illustrates the statement that peptones are not to be found in the circulating blood, even after a full proteid diet. In this connection it is to be remembered that we have abundant proof of the rapid disappearance of both proteoses and peptones[211] from the intestine, either by absorption or otherwise. They certainly disappear, and, as we have seen, are not to be found in the blood. Further, Neumeister has confirmed the original observation of Schmidt-Mulheim,[212] that both chyle and lymph are practically free from proteoses and peptone, thus again forcing us to the conclusion that the primary products of proteolysis must undergo change prior to their passage into the blood or lymph.