Many observations lend favor to the view that a transformation of some kind takes place in the intestine itself, not indeed in the lumen of the tube, but somewhere in the walls, through which the peptones must pass before reaching the blood. Thus, peptones placed in contact with pieces of the isolated, though still living, intestine, after a time completely disappear from view,[213] so completely that no reaction can be obtained even by the most delicate of tests. In support of this statement I may cite the results of several of my own experiments which certainly furnish evidence that true peptones undergo profound alteration by simple contact with the living mucous membrane of the small intestine. The method employed was similar to that made use of some years ago in a study of the influence of peptone on the post-mortem formation of sugar in the liver.[214] A large, well-nourished rabbit was killed by severing the carotid artery and the blood collected and defibrinated. Of this, 50 c. c. were mixed with an equal volume of 0.5 per cent. salt solution containing 1.25 grammes of pure amphopeptone, prepared from egg-albumin, the mixture obviously containing 1.25 per cent. of peptone. The fluid was transferred to a large, roomy flask, provided with a stopper having two holes, in one of which was fitted a long glass tube reaching below the fluid. The flask, with its contents, was then placed in a suitable water-bath at a temperature of 40° C.
The small intestine of the rabbit was carefully separated from the mesentery and from the pancreatic gland, and the upper portion cut open and quickly washed free from any contained matter or adherent secretions, by repeated immersion in 0.5 per cent. salt solution warmed at 40° C. This was repeated until the tissue was quite free from all impurities, after which it was cut into small pieces and immersed for a moment in a 0.5 per cent. solution of sodium chloride containing 1.25 per cent. of peptone. The tissue was then carefully collected on coarse muslin, allowed to drain, and then quickly transferred to the flask containing the warm blood and peptone. This mixture was kept at 40° C. for two hours, a slow current of air being bubbled through the fluid during the entire period. At the expiration of this time the fluid was separated from the pieces of tissue by nitration through muslin, and then saturated with ammonium sulphate after the usual method for the separation of albumoses, etc. On now testing a portion of the clear filtrate for peptone by the biuret test, not a trace of a reaction could be obtained. The entire amount of proteid matter present was precipitated by the ammonium salt, thus showing that the peptone originally added had been completely transformed into something precipitable by saturation of the fluid with ammonium sulphate. That this transformation of the peptone was accomplished mainly through the action of the intestine, was shown by a parallel experiment, in which all of the above conditions were duplicated, omitting only the pieces of intestine. Here, however, on testing the filtrate from the ammonium sulphate-precipitate, a strong biuret reaction was obtained, thus proving the presence of at least some unaltered peptone.
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. Still, this form of deuteroproteose, β deuterocaseose, as I have elsewhere noted, is very slowly precipitated by the ammonium salt. Consequently, it is an easy matter to demonstrate that this proteose, on treatment with the intestinal mucosa in the presence of blood at the body-temperature, is transformed into something completely and readily precipitable by ammonium sulphate; the filtrate from the latter failing to show any biuret reaction, although the corresponding control experiment without the intestine gives a bright violet color with cupric sulphate and potassium hydroxide.
Hence, we are certainly justified in saying that both peptones and proteoses undergo some retrogression when in contact with the walls of the intestine. Moreover, there is some evidence that the proteoses, before undergoing such a transformation, are first converted into peptone by the action of the intestinal walls, a statement which will apparently apply to both the primary and secondary proteoses. This primary action of the intestinal walls is not considered as due to any adherent trypsin, or to possible traces of succus entericus, but rather as a part of the action of the living epithelial cells, or perhaps as connected with the possible presence of lower organisms not removable from the intestinal wall by ordinary washing.
The transformation of peptones by the substance of the intestine is apparently common to the intestinal tract of many animals, and perhaps to all, and indeed can also be accomplished by the liver.[215] This latter fact is of some importance, since it adds weight to the supposition that this peculiar action of the intestine cannot be due to the possible presence of trypsin; a view which is strengthened by the fact that a glycerin-extract of the intestine has no action on amphopeptone. Certainly, the latter shows no diminution in the strength of the biuret reaction after long contact at body temperature with such an extract. Further, it has been shown that antipeptone, which is not affected by the pancreatic enzyme, suffers the same change as amphopeptone by contact with the intestine. Far more probable is it that retrogression or transformation of peptone by the substance of the intestine, is due to the vital activity of some or all of the epithelial cells of the intestinal mucosa; a characteristic possibly shared by some or all of the hepatic cells of the liver. The kidney-cells certainly do not possess this power, but we can see a special fitness in the liver-cells being endowed with the ability to quickly break down, or transform, any peptone or proteose that might by chance escape unaltered from the intestinal tract. Shore,[216] however, inclines to the view that the hepatic cells do not possess this power to any great extent, in opposition to the older views of Plòsz and Gyergai,[217] as well as of Seegen[218] and of Neumeister.
With reference to the action of the stomach-mucosa on proteoses, it has been shown[219] that when relatively large amounts (5 grammes) are introduced into the stomach of a rabbit, the pylorus being ligatured, both proteoses and peptones may appear in the urine, thus indicating that while they may be absorbed to some extent under the above conditions, the proteoses are not readily transformed into native proteids without exposure to the intestine. Smaller amounts (2 grammes), however, may, under the above conditions, be completely transformed; at least Hildebrandt claims this to be the case, mainly on the ground that after the introduction of albumoses into the stomach, the pylorus being ligatured, no trace of them can be found in the urine. The same observer also claims that blood-serum, in the case of dogs, is able to transform albumoses into ordinary serum-globulin. Certainly, after intra-venous injection, proteoses disappear from the blood, but, as we shall see later on, a certain amount, at least, may be transferred to the lymph. It is also claimed that when albumoses are injected subcutaneously, neither albumoses nor peptones are to be detected in the urine. This, however, seems hardly probable in the light of what has been said, and especially in view of the fact that Neumeister’s experiments tend to show that even 0.1 gramme of albumoses introduced subcutaneously may give rise to temporary albuminuria.
Assuming for the moment that the chief products of proteolysis, i. e., the proteoses and peptones, are, during the act of absorption, transformed through the vital processes of the epithelial cells of the intestine into serum-albumin, or globulin, and absorbed as such into the blood, we may well consider whether such transformation, i. e., a retrogression into a native proteid again, is inconsistent, or out of harmony, with the general character of the changes known to occur in the body. In attempting to answer this question we need not look far to find a perfectly analogous case. Thus, in the digestion of starchy foods by the amylolytic ferments of both the saliva and the pancreatic juice, the carbohydrate material undergoes hydration with formation of dextrins and maltose, the latter, at least, being quickly absorbed into the circulating blood. 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. Thus, according to the recent work of M. C. Tebb,[220] the mucous membrane of the intestine has the power of transforming maltose into dextrose; simple warming at 40° C. of a solution of maltose in 0.5 per cent. sodium carbonate with a few grammes of the dried mucous membrane from the intestine, being sufficient to insure a marked conversion of maltose into the higher-reducing sugar, dextrose. This observation, I can confirm from experiments just completed in my own laboratory. This action is presumably due to a ferment, which, according to Tebb, is widely distributed throughout the body, being present not only in the intestine, but also in the liver, kidney, spleen, striated muscle-tissue, and, indeed, in the blood-serum; so that it would appear that nearly all the tissues of the body are endowed with the power of transforming maltose into dextrose. These statements being correct, it would seem that, while the amylolytic ferments of the several digestive juices transform, by hydrolytic action, starchy foods into maltose, the latter is exposed during its passage through the intestinal wall, as well as in the blood itself, to another ferment which carries the hydration still further, with formation of dextrose; and yet the latter product is destined, in part at least, to undergo retrogression into a starch-like body, i. e., glycogen, before it is completely utilized by the system. Thus, the analogy between these carbohydrate bodies and the products of proteolysis is complete, and we may well accept the statements already made regarding the ultimate fate of the proteoses and peptones formed during proteolysis, as in no way inconsistent with the general tenor of events going on in the body.
While we are inclined to believe that the chemical changes attending the absorption of proteoses and peptones occur mainly in the epithelial cells of the intestinal mucosa, and that there is a direct transference of the alteration-products to the blood, there are still other views that cannot be wholly ignored. Thus, the view originally advanced by Hofmeister,[221] in which special stress is laid upon the functional activity of the leucocytes of the adenoid tissue surrounding the intestine, demands some consideration. The theory supposes that these cells not only have the power of taking up peptones, but also of assimilating and transforming them into the cell-protoplasm. This view being correct, it is plain that the so-absorbed proteid must pass into the circulating blood through the thoracic duct, and Hofmeister further considers it probable that the lymph-cells of the mesenteric glands can transform any absorbed peptone that may escape the leucocytes of the adenoid tissue.