Trypsin

“ 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. ”

“ Otherwise, the composition of the improved bate quite coincides qualitatively with the composition of dogs’ dung, as the latter actually consists in addition to the unabsorbed portions of food, of secretions of gall, the pancreatic gland and the mucous membrane of the intestines. The trypsin and steapsin respectively as well as being derived from the pancreatic juice, may also be derived from the vegetable kingdom, for instance, there are considerable quantities of trypsin in the sap of the fig. Steapsin, in not inconsiderable quantity, is found in the saps of flax, hemp, maize, etc. ”

“ 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. ”

“ Some proteins, the albuminoids and racemized proteins, resist tryptic digestion but yield to acid hydrolysis. We know also that some NH-CO linkages of proteins are broken down with great difficulty by trypsin as it is difficult to obtain a tryptic digest of protein which does not give the biuret reaction, and the work of Fischer and Abderhalden has shown that certain artificial polypeptides are not digested by pure activated pancreatic juice. ”

“ 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. ”

“ One cannot fail to be impressed with the resemblance in functional power between the unformed ferments as a class and cell-protoplasm. To what can we ascribe the particular functional power of each individual ferment? Why, for example, does pepsin act on proteid matter only in the presence of acid, and trypsin to advantage only in the presence of alkalies? Why does pepsin act only on proteid matter, and ptyalin only on starch and dextrins? Why does trypsin produce a different set of soluble products in the digestion of albumin than pepsin does? ”

“ Expressed in different language, pancreatic juice as it is secreted by the gland does not contain ready-formed trypsin; it does contain, however, an inactive pro-enzyme, which, under the influence of a specific substance contained in the intestinal mucous membrane, known as enterokinase, is transformed into the active enzyme trypsin. There is thus seen another suggestive example of the close physiological relationship between the small intestine and the activity of the pancreatic gland, or its secretion.
The chemical changes taking place in the small intestine are many and varied. ”

“ The secretion of some digestive glands would prove poisonous if absorbed unchanged. For example, the trypsin of the pancreas (see Nutrition) digests albuminous bodies in neutral or alcoholic solution, and if the whole of that which is secreted in the pancreas for the digestion of meat in the intestine were absorbed unchanged into the circulation, it would digest the body itself and quickly cause death. The secretion of trypsin by the pancreas may therefore be looked upon as the formation of a toxin. ”

“ Secretogen Tablets, said to be “prepared from prosecretin and succus entericus obtained from the epithelial cells of the duodenum, combined with pancreatic extract”; Kinazyme, “a preparation of extract of spleen, reinforced with trypsin, amylopsin and calcium lactate.”
While great claims have been made for Trypsogen and while it has been most widely advertised, it is the consensus of opinion of the most eminent students of the question that pancreas is not really efficacious in diabetes. ”

“ How little adequate tinctorial differences by themselves are to settle the chemical identity of a granulation, is at once evident on consideration of the granules of other organs. No one surely would assert, that a liver, muscle, or brain cell could occasionally secrete trypsin, simply because the granules of the pancreas stain similarly and analogously to those of the cells mentioned. ”

“ The work which is quoted against the Council was undertaken by the Council itself, to clarify obscurities in the older data. The outcome of these new investigations showed the essential correctness of the deductions from the older work, namely, that pancreatin is destroyed by pepsin-hydrochloric acid. Dr. Long’s work to which the firm’s reply evidently refers, showed that under favorable conditions, namely, when protected by an excess of protein, some trypsin may escape destruction in the stomach ”

“ One might naturally reason that, with the facilities for rapid absorption that exist in the small intestine, trypsin-proteolysis would rarely proceed beyond the peptone stage, yet we have ample evidence that, under some circumstances at least, both leucin and tyrosin are formed in considerable quantities in the intestine.
It obviously makes a very great difference to the economy in what form the proteid matter ingested leaves the intestine on its way into the blood-current. ”

“ Of these the longest known and best studied are those which are produced by toxins, and which neutralize the action of the toxins upon the animal organism (anti-toxins) .109 Normal serum also inhibits the action of trypsin and many other enzymes. Another very important group of anti-bodies are the precipitins. If the serum of an animal be injected repeatedly into another animal of different species, a precipitin appears in the serum of the animal treated, which causes a precipitate when added to the serum of the first animal. ”

“ Again, trypsin exhibits its peculiar proteolytic power in the presence of sodium carbonate, a salt which has an immediate destructive action upon pepsin. Hence, a medium which is favorable for the action of the one ferment may be directly antagonistic to the action of the other. ”

“ While there is a great variety of enzymes which may be produced by a single individual organism, the same enzyme may be found in the greatest variety of organisms; as, for example, the protease trypsin, which has been found in several species of bacteria, in the carnivorous plant known as "Venus' Fly Trap," and in the human pancreas, as well as that of all other animals. ”

“ The primary and secondary products of pepsin-proteolysis, as well as unaltered proteids, are alike subject to these changes, and bodies of the simplest constitution may result in both cases from the series of hydrolytic changes set in motion by this proteolytic enzyme. The power of the ferment as a contact agent is astonishing, for in the case of trypsin no accessory body is necessary to bring out its latent power. Water, proteid, and the enzyme at the body-temperature are all that is necessary to call forth prompt and energetic hydrolytic action. ”

“ Fermi seems to be inclined to think that the “living molecule” of protein is not hydrolysable (perhaps because the enzyme cannot attach itself to it?) , while a change in the constitu­tion or configura­tion of the proteins takes place after respira­tion has ceased. The fact that the living cell resists the digestive action of trypsin and pepsin has found two other modes of explana­tion, first, that the cells are surrounded by a membrane or envelope through which the enzyme cannot diffuse, and second, that the living cells possess antiferments. ”

“ The nourishment is first digested in the cavity of the digestive tube by secreted juices, and its treatment is completed within the amœboid cells of the cæcum.
In higher animals, the digestion of food is due to several digestive ferments (rennet, pepsin, trypsin, enterokinase, etc.) produced by divers organs (stomach, pancreas, intestines) . The phagocytes also manufacture several digestive ferments; their principal digestive juice is a soluble ferment of the trypsin category, to which Metchnikoff gave the name of cytase. ”

“ Trypsin, trip′sin, n. a ferment which occurs in the secretion of the pancreas, and may be isolated from the pancreatic juice, as pepsin from the gastric.—adj. Tryp′tic.—n. Tryp′tōne, a substance formed from proteids by pancreatic juice. [Gr., from tribein, to rub, the substance having been first found on rubbing down the pancreas with glycerine.]
Trysail, trī′sāl, or trī′sl, n. a reduced sail used by small craft, instead of their mainsail, in a storm: a small fore-and-aft sail set with a boom and gaff. ”

“ Physiol. Chem. xli. f. 153 (1904) . See also the articles by Mr. A. Seymour Jones, B.Sc., writing under the pseudonym of “Heof Joppa,” in the Leather Trades’ Review, July 19, 1911, p. 540; and Aug. 16, 1911, p. 625.
100 See, however, the recent paper by Eberle and Krall, Ueber den Nachweis des Trypsins im Hundekot, Collegium 1911, p. 201, in which the authors endeavour to show the presence of unchanged trypsin in dog dung. Their proof depends upon the action of an antipancreatic serum on infusions of dog dung based on the work of Achalme, Ann. de l’Inst. ”

“ The optimum temperature for zymase action is 28° to 30°. The enzyme is killed by heating to 45° to 50° in solution, or to 85° if in dry preparation.
Proteases of the erepsin type, i.e., those which break proteins down to amino-acids instead of only to the proteose or peptone stage, as is characteristic of the enzymes of the trypsin type, are widely distributed in plants. Except in the case of the two which occur in large amounts in certain special fruits (papain in papaws, and bromelin in pineapples) , they are very difficult to prepare in pure form for study. ”

“ We find illustrations of such antiferments in the gastro-intestinal tract, by the presence of which the digestive enzymes are restrained from attacking the proteins of the tissue cells, composing the lining membranes of the intestine. Apparently, there is no reason why the enzymes pepsin, trypsin, etc., which digest so vigorously the various protein foodstuffs should not attack with equal avidity the related proteins present in the mucous membranes of the stomach and small intestine. ”

“ Dilute alkali favors oxidation and dilute acid favors the reduction. Light favors the reduction of oxyluciferin.
Apparently luciferin and oxyluciferin have identical chemical properties. Neither is digested by the enzymes: malt diastase, ptyalin, yeast invertase, pepsin, trypsin, steapsin, amylopsin, rennin, erepsin, urease or enzymes occurring in the water extracts of dried spleen, kidney, or liver. Luciferase is destroyed only by pepsin (probably) , trypsin, erepsin, and something in spleen and liver extract. ”

“ Physiologists hastened to formulate a theory which would harmonize with existing views, and so arose the theory of "luxus consumption," in which it was held that when an excess of protein food was taken, far larger than the demands of the body called for, the organism was able to protect itself by virtue of this power possessed by trypsin of breaking down protein matter into simple decomposition products easily got rid of with less strain upon liver, kidneys and other organs and tissues. ”

“ The solids include mineral salts (the chief of which is sodium carbonate) and four different chemical agents, or enzymes,—trypsin, amylopsin, steapsin, and a milk-curding enzyme. These active constituents make of the pancreatic juice the [pg 156] most important of the digestive fluids. It acts with vigor on all of the nutrients insoluble in water, producing the following changes:
1. It converts the starch into maltose, completing the work begun by the saliva. This action is due to the amylopsin,61 which is similar to ptyalin but is more vigorous. ”

“ The direct action of commercial trypsin on boiled yeast-juice also yielded [p068] a negative result, although this cannot strictly be regarded as an indication of the effect of the specific proteoclastic enzymes of yeast-juice. On the other hand, it was found that when boiled juice was treated for some time with an emulsion containing the lipase of castor oil seeds, the co-enzyme was completely destroyed. This is a result of great importance, inasmuch as it probably indicates that the co-enzyme is chemically allied to the class of substances hydrolysable by lipase, i.e. ”

“ On the other hand, luciferin has two properties which to say the least are unusual for proteins. I refer to its [Pg 121] solubility in alcohols, acetone, esters, etc., and non-digestibility by trypsin or erepsin, which have almost universal proteolytic power.
The best known class of proteins soluble in alcohol is the prolamines of plants, but the prolamines are insoluble in water and in absolute alcohol. Zein, the prolamine of corn, is soluble in 90 per cent. ethyl, methyl, and propyl alcohols, in glycerol heated to 150° C., and in glacial acetic acid. ”