Pepsin

PEPSIN (pepsinase), a proteolytic enzyme belonging to the group of proteases (see Proteases). It is characterized by optimal activity at pH = 1.4–2.5, i.e., at such a concentration of H⁺ ions at which other proteolytic enzymes are destroyed; P. brings about the splitting of proteins only to the stage of albumoses and peptones. P. was discovered by Schwann in 1836; found in the stomach of all vertebrates except some fish; is secreted mainly by chief cells (see) of the glands of the fundal part of the stomach and pyloric glands. "In frogs it is secreted by the glands of the lower part of the esophagus; in some invertebrates there is an enzyme similar in its action to P. Pepsin is soluble in glycerin, a weak solution of NaCl, diluted acids; it is precipitated by NH₄Cl, alcohol. It is sensitive to strong acids and alkalis; the latter destroy it even at minimal concentrations. The action of P. is inhibited by products of peptic digestion already in an amount of 1%, salicylic acid, carbolic acid, ether, chloroform, tannin, cane and grape sugar, bile, large amounts of alcohol, and almost all salts of heavy metals. Caffeine and small amounts of arsenites favor the action of P. The most active preparations of P. are obtained by the method of Hammarsten by partially saturating a solution of the mucous membrane of the pylorus with 0.2% HCl, dissolving the filtered hyaline precipitate in 0.2% HCl, repeating the above precipitation and dissolution twice, and finally dialyzing the resulting acidic solution. P. acts on almost all proteins and is, among other things, the most energetic enzyme acting on collagen of connective tissue. P. does not act on keratin, spongine, conchinoline. The opinion previously expressed that P. is not a hydrolytic enzyme, that it merely disaggregates colloidal particles of protein without breaking the chemical peptide bonds in the molecule of the latter, is now abandoned, since careful experiments have shown that even with the action of P. there is an increase in free carboxyl and amino groups; but the matter is limited to fragmentation into still relatively large complexes, and the separation of individual amino acids does not occur. The optimum of action of P. lies at the body temperature of the animal; a temperature of 65° destroys P. The usual formulation that inactive pepsin (pepsinogen) is activated by HCl must be changed in the sense that the enzyme secreted by the glandular cells is capable of manifesting its action only at a certain concentration of H⁺ ions. There is no actual activation in this case, and with a decrease in the concentration of H⁺ ions the action of P. ceases again. In 1930, Northrop obtained a crystalline preparation from commercial P., which possessed all the typical properties of a protein, denaturing upon heating and under the influence of alkalis, and the degree of denaturation corresponded exactly to the loss of activity. Denaturation is partially reversible, and in exactly the same way the enzymatic activity of the preparation is restored. Northrop considers that the crystallizing protein obtained by him is P. The kinetics of the chemical action of pepsin is expressed by the Schutz-Borisov rule: the relative amounts of protein digested in 1 hour are proportional to the square roots of the relative amounts of P. V = hVF. Derived on the basis of experiments with impure preparations and without sufficiently strict observance of all conditions of the enzymatic reaction, this rule has now lost its significance. Among the methods for the quantitative determination of P., the method of Miett is common. The determination of P. in urine by Ellinger and Scholz is based on the action of P. on a solution of casein followed by salting out the residue of undigested casein with sodium acetate. P. is found in the blood and urine. The change in the amount of P. in gastric juice is not parallel to the changes in the amount of HCl and the amount of juice, especially in pathological cases (in sub- and anaciditas); the complete disappearance of P. is rare, according to Faber a decrease in P. is an early symptom of achylia. Giinzburg and Loeper consider an increase in the amount of P. on an empty stomach to be pathognomonic for gastric and duodenal ulcer. On the other hand, Katsch considers the quantitative determination of P. in gastric juice to have no diagnostic significance. The strongest pharmacological stimulator of P. secretion is histamine. By the work of I. P. Pavlov, the connection between the nature of food and the amount of P. was established for the first time. A number of harmful factors influence pepsin secretion: for example, soluble and insoluble salts of lead introduced into the stomach stably lower the amount of P. (Razenkov, Grinberg); the same has been established in relation to zinc oxide. Aniline gives a non-stable increase in P. secretion, alternating with a non-stable decrease. Benzene causes a prolonged decrease in P. secretion. There are many preparations of P., differing from each other in physical properties, mainly solubility in water, and method of preparation. In order for the pharmacopoeial P. to manifest its action, it must be administered with HCl. P. is prescribed for dyspepsias associated with a decrease in gastric secretion (benign achylia, intractable vomiting of pregnancy). The prescription of P. has only a substitutive value. Dose: 0.2–0.6 one or two times a day before meals; the prescription of the Moscow Health Department: Rp. Pepsini 0.6; Ac. mur. dil. gtt. X; Aq. destil. 60,0; one tablespoon before meals. Previously, attempts were made to apply P. for dissolving diphtheritic membranes, as well as for dissolving tissue and cancerous growths. In veterinary medicine, P. is applied against bloating in ruminants and against retention of urine. Regarding the assumption of the identity of P. and the rennet enzyme, see Chymosin.

N. Topkachevskaya. Preparations of P. Soluble (extracts) and insoluble preparations are distinguished. The quality of both types is determined by their ability to digest protein; this ability is expressed in conditional units. According to F VII, a unit is an equal amount of boiled hard and rubbed through a sieve No. 5 (10 x 10 holes per 1 cm²) of chicken egg white taken for the test; thus, a "100 units" valer, or, as is usually written, "1:100", means that under pharmacopoeial conditions of temperature, duration of the experiment (40–45°, 4 hours), etc., 1 part of the test preparation digests 100 parts of boiled protein. According to Gross (casein purified by Hammarsten is used as the protein), 4 Gross units correspond approximately to one pharmacopoeial unit. 1. Pepsin F VII, Pepsinum saccharatum or Pepsinum rossicum, is prepared from more concentrated preparations by diluting them with milk sugar to obtain a preparation with a strength of action 1:100. The preparation must dissolve in water containing 0.25% HCl. According to F VII, the formation of a slightly turbid solution with pure water is allowed. 2. Pepsin 1:3000, from which the previous preparation is made, is a water extract from the mucous membrane of the stomachs of pigs, sheep, or calves. The preparation is soluble in water. 3. Acidol-pepsin, Acidol-Pepsin, a mixture of pepsin (1:100) with acidol; due to the extremely easy hydrolysis of acidol, this preparation allows P. and the necessary HCl for its action to be present in a dry form (imported preparation). 4. Gastrol - dried mucous membrane of the stomachs of animals possessing pepsin action. 5. Dog gastric juice (Institute of Experimental Medicine, laboratory of Academician I. P. Pavlov in Leningrad) represents natural (fistular) gastric juice, the secretion of which is caused by simulated feeding of dogs with an esophageal fistula and a gastric fistula. Activity is variable but usually very high. 6. Ingluvin - P. from the goiter of chickens (American preparation).