Читать книгу On Digestive Proteolysis - R. H. Chittenden - Страница 6

In digestive proteolysis we have a branch of physiological study which of late years has made much progress. Chemistry has come to the aid of physiology and by the combined efforts of the two our knowledge of the digestive processes of the alimentary tract has been gradually broadened and deepened. That which at one time appeared simple has become complex, but increasing knowledge has brought not only recognition of existing complexity, but has enabled us, in part at least, to unravel it.

By digestive proteolysis is to be understood the transformation of the proteid food-stuffs into more or less soluble and diffusible products through the agency of the digestive juices, or more especially through the activity of the so-called proteolytic ferments or enzymes contained therein; changes which plainly have for their object a readier and more complete utilization of the proteid foods by the system.

In selecting this topic as the subject for this series of Cartwright Lectures I have been influenced especially by the opinion that both for the physiologist and the physician there are few processes going on in the animal body of greater importance than those classed under the head of digestion. Further, few processes are less understood than those concerned in this broad question of digestive proteolysis, especially those which relate specifically to the digestion of the various classes of proteid food-stuffs, and to the absorption and utilization of the several products formed. Moreover, the subject has ever had for me a strong attraction as presenting a field of investigation where chemical work can advantageously aid in the advance of sound physiological knowledge; and certainly every line of advance in our understanding of the normal processes of the body paves the way for a better and clearer comprehension of the pathological or abnormal processes to which the human body is subject.

You will pardon me if I specially emphasize in this connection the fact that advance along the present lines was not rapid until physiologists began to appreciate the importance of investigating the chemico-physiological problems of digestion by accurate chemical methods. Something more than simple test-tube study, or even experimental work on animals, is required in dealing with the changes which complex proteids undergo in gastric and pancreatic digestion. The nature and chemical composition of the proteids undergoing digestion, as well as of the resultant products, are necessary preliminaries to any rightful interpretation of the changes accompanying digestive proteolysis; but physiology has been slow to appreciate the significance of this fact, and, until recently, has done very little to remedy the noticeable lack of accurate knowledge regarding the composition and nature of the proteid and albuminoid substances which play such an important part in the life-history of the human organism, either as food or as vital constituents of the physio­logically active and inactive tissues. 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? Surely, in no other way can we measure the nature or extent of the changes involved in the various phases of proteolysis than by a thorough study of chemical composition and constitution, as well as of chemical reactions and general properties.

In the early history of physiology there was, quite naturally, little or no thought given to the nature of proteolytic changes. The gastric juice, as one of the first digestive fluids to be studied, was recognized as a kind of universal solvent for all varieties of food-stuffs, and this even long before anything was known regarding its composition, but beyond this point knowledge did not extend. Active study of the gastric juice, as you well know, dates from 1783, when the brilliant Italian investigator Spallanzani commenced his work on digestion. The names of Carminati, Werner and Montégre1 are also associated with various phases of work and speculation in this early history of the subject, especially those which pertained to the possible presence of acid in the stomach juices. In 1824, however, Prout showed conclusively that gastric juice was truly acid, and, moreover, that the acidity was due to the presence of free hydrochloric acid, and not to an organic acid. Still, many observations failed to show the presence of an acid fluid in the stomach, and it was not until Tiedemann and Gmelin’s2 masterly researches were published that the cause of this discrepancy was made clear. It was then seen that the secretion of an acid gastric juice was dependent upon stimulation or irritation of the mucous membrane of the stomach, and that so long as the stomach was free from food or other matter capable of stimulating the mucosa, it contained very little fluid, and that neutral or very slightly acid in reaction. These early observers also recorded the fact that the amount or strength of acid increased with the outpouring of the secretion, incidental to natural or artificial stimulation, thus giving a hint of the now well-known fact that any and every secretion may show variations in composition incidental to the character and extent of the stimulation which calls it forth.

The period between 1825 and 1833 was characterized especially by the presentation of the many results bearing on gastric digestion obtained by Dr. Beaumont on Alexis St. Martin, followed a little later, in 1842, by a long period of experimenta­tion by many physiologists, as Blondlot,3 Bassow,4 Bardeleben,5 Bernard,6 Bidder and Schmidt,7 and many others on methods of establishing gastric fistulæ on animals, by which many interesting results were accumulated regarding the physiology of gastric digestion. Up to 1834, however, there was no adequate explanation offered of the solvent power of the stomach juice; aside from the presence of hydrochloric acid, nothing could be discovered by the earlier chemists to account for the remarkable digestive action. Eberle,8 however, attributed to the mucous membrane of the stomach a catalytic action, and claimed that it only needed the presence of a small piece of the stomach mucosa with weak hydrochloric acid for the manifestation of solvent or digestive power. It remained for Schwann,9 to show the true explanation of this phenomenon, and although he was unable to make a complete separation of the active principle which he plainly believed existed, he gave to it the name of pepsin. Wassmann, Pappenheim,10 Valentin, and later Elsässer,11 all endeavored to obtain the substance in a pure form, and Wassmann,12 in 1839, surely succeeded in obtaining a very active preparation of the ferment—one capable of exerting marked digestive action when mixed with a little dilute acid. Thus, a true understanding of the general nature of gastric juice was finally arrived at, and the cause of its digestive power was rightfully attributed to the presence of the ferment pepsin and the dilute acid. Further, the analysis of human gastric juice made by Berzelius,13 in 1834, showed that the secretion contains very little solid matter (1.26 per cent.), thus calling attention to the fact that the digestive power of this fluid is out of all proportion to the amount of pepsin, or even to the amount of total solid matter present, and consequently paving the way for a general appreciation of the peculiar nature of the dominant body, i.e., the pepsin.

The original conception regarding the manner in which gastric juice exerts its solvent power on proteid foods was apparently limited to simple solution; chemical solution if you choose, brought about by catalytic action, but without any hint as to the possible nature of the soluble products formed. Mialhe,14 however, recognized the fact that this transformation, by which insoluble and non-diffusible proteid matter was converted into a soluble and diffusible product, was a form of hydration, comparable to the change of insoluble starch into soluble sugar, and he named the hypothetical product albuminose. Mialhe’s study of the matter in 1846 was followed by Lehmann’s15 investigation of the subject, and the coining of the word peptones as an appropriate name for the soluble products of gastric digestion. The peptones isolated by Lehmann were described as amorphous, tasteless substances, soluble in water in all proportions and insoluble in alcohol. They were likewise precipitated by tannic acid, mercuric chloride, and lead acetate, and were considered as weak acid bodies, having the power of combining with bases to form salts of a more or less indefinite character. Twelve years later, in 1858, Mulder16 gave a more complete description of peptones, but his study of the subject failed to advance materially our knowledge of the broader questions regarding the nature of the process, or processes, by which the so-called peptones were formed. A year later, in 1859, Meissner17 brought forward the first of his contributions, and during the following three or four years several communications were made representing the work of himself and pupils upon the question of gastric digestion, or more especially upon the character of the products resulting from the digestive action of pepsin-hydrochloric acid.

The general tenor of Meissner’s results is shown in the description of a row of products as characteristic of the proteolytic action of pepsin-acid on proteid matter. In other words, there was a clear recognition of the fact that proteid digestion in the stomach, through the agency of the ferment pepsin, is something more than a simple conversion of the proteid into one or two soluble products. The several bodies then isolated were named parapeptone, metapeptone, dyspeptone, α, β, and γ peptone; names now seldom used, but significant as showing that at this early date there was a full appreciation of the fact that digestive proteolysis as accomplished by the ferment pepsin is an intricate process, accompanied by the formation of a series of products which vary more or less with the conditions under which the digestion is conducted.

This was the commencement of our more modern ideas regarding digestive proteolysis, but only the commencement, for it ushered in an era of unparalleled activity, in which Brücke, Schützenberger, and Kühne each contributed a large share toward the successful interpretation of the results obtained. Further, knowledge regarding the proteid-digesting power of the pancreatic juice was rapidly accumulating, thus broadening our ideas regarding digestive proteolysis in general. Corvisart18 had called attention to the proteolytic power of the pancreatic juice in 1857, and although his observations were more or less generally discredited for a time, they were eventually confirmed by Meissner,19 Schiff, Danilewsky,20 and Kühne,21 the latter particularly contributing greatly to the development of our knowledge concerning this phase of digestive proteolysis. The proteolytic power was proved to be due to a specific ferment or enzyme, now universally called trypsin, which digests proteid foods to the best advantage in the presence of sodium carbonate. Digestive proteolysis in the human body was thus shown to be due mainly to the presence of two distinct enzymes, the one active in an acid fluid, the gastric juice, the other in an alkaline-reacting fluid, the pancreatic juice, but both endowed with the power of digesting all varieties of proteid foods, with the formation of a large number of more or less closely related products.

So much for the early history of our subject, and now, without attempting any exhaustive sketch of its gradual development during the last decade and a half, allow me to present to you digestive proteolysis as it stands to-day, developed somewhat, I trust, by the results I have been able to contribute to it during the last twelve years.