CATHEPSINES — group of fabric desmoenzymes — the endopeptidases (peptidit — peptidgidrolaz) splitting internal peptide bonds in proteins and peptides; carry out intracellular disintegration of proteins and perform important regulatory function, participating in education and an inactivation of a number of enzymes, hormones, biologically active proteins and peptides.
At some fiziol, (e.g., involution of a uterus after pregnancy) and patol, states (muscular dystrophy, various inflammatory processes: pseudorheumatism, gout, emphysema of lungs, etc.) increase in activity is observed To. in fabrics that is connected with an exit of enzymes from lysosomes. To. are found practically in all animal fabrics.
The highest activity To. is defined in a liver, a spleen, ferruterous fabric, the englobing cells (macrophages and polymorphonuclear leukocytes), and also in quickly growing and sharing cells.
On the basis of data on functional groups, an active center and the mechanism of action To. subdivide into 4 groups: carboxyl, thiol, serinovy proteinases and metalproteinases. D, E cathepsines, active in acid medium, and a renin belong to carboxyl proteinases; their activity is oppressed by diazocarbonyl compounds in the presence of ions of Cu 2+ and pepstatiny — peptide of a microbic origin. Cathepsine D is found in all fabrics, localized in lysosomes, begins intracellular disintegration of proteins. It hydrolyzes the bonds formed by the remains of hydrophobic amino acids. Pier. the weight of it To. apprx. 40000.
The renin is high-specific proteinase of kidneys; participates in formation of angiotensin I, splitting one peptide bond in angiotensinogen. To thiol To. B1, H, L cathepsines and a number of the enzymes close to them on properties belong. Inhibitors K. the substances blocking SH groups are: n-hlormerkuribenzoat, iodacetic to - that, N-etilmaleinimid, etc.; the maximum activity To. it is shown in the presence of thiol connections. B1 cathepsine is found in various fabrics, localized in lysosomes; splits many proteins, including collagen and proteoglycan, at pH 5,0 — 6,0 in the neutral environment causes an inactivation of a number of cytoplasmatic enzymes; pier. weight apprx. 25 000. In group serinovy To. (serinovy proteinases) elastase, cathepsine G, a plasminogen activator and many other proteinases, active in neutral and alkaline condition enter; are inactivated diizopropilftorfosfaty. The elastase hydrolyzing elastin, and cathepsine G are emitted from polymorphonuclear leukocytes, macrophages and some fabrics; they split proteoglycan, collagen and some other proteins. Pier. weight of elastase 30 000 — 34 000, and G 20 000—23 000 cathepsine. The collagenase and some other the enzymes inhibited by the substances forming inner-complex (chelate) compounds with metals belongs to metalproteinases: EDTA, 1,10 — phenanthroline, etc. A collagenase — it is high - specific proteinase — is found in many fabrics, catalyzes the beginning of degradation of collagen in fiziol, conditions.
At blood serum, many cells and fabrics there are inhibitors oppressing activity To. It, and also structural isolation of the majority To. inside lysosomes (see) and other organellas protects intracellular proteins from splitting. Intracellular disintegration of proteins proceeds hl. obr. in lysosomes where proteins get as a result of endocytosis. At damage of fabrics, and also under the influence of a number of factors (some hormones, toxins, cell-bound immune complexes, etc.) there is an exit To. from cells. It is observed as at fiziol., and at patol, states and in some cases is followed by local increase in proteolytic activity.
Changes in tissues of a uterus at its involution after pregnancy and during the healing of wounds, proteolysis at certain stages of an embryogenesis and at diseases of various etiology (a pseudorheumatism, a glomerulonephritis, emphysema of lungs, cirrhosis, muscular dystrophy, etc.) are result of action defined To.: collagenases, elastases, B1, G cathepsines, etc. To. polymorphonuclear leukocytes and macrophages play an important role in development acute and hron, inflammations (see) since some of them (SH dependent proteinase, a kininogenaza, cathepsine D) cause formation of factors of permeability, chemotactic factors, etc. can activate a complement, splitting S3-and C5 components with formation of anaphylatoxins. Consider that To. participate in a pathogeny of autoallergichesky diseases where their role in some cases can be connected also with formation of autoantigens (e.g., at encephalomyelitis). Increase in activity To. at some diseases (e.g., emphysema of lungs) it can be caused by deficit or inborn insufficiency of inhibitors. To. participate in antibacterial protection of an organism, lyseing some bacteria and splitting the alien elements taken in the course of phagocytosis.
See also Peptide-hydrolase .
Bibliography: Yeliseyev Yu. E., etc. Karboksikatepsin — key enzyme of two systems regulating blood pressure, Vopr. medical chemistry, t. 16, No. 6, page 646, 1970; Mosolov V. V. Proteolytic enzymes, M., 1971, bibliogr.; Pokrovsky A. A. and Tute of l I am V. A N. Lysosomes, M., 1976, bibliogr.; Chemotaxis, ed. by E. Sorkin, Basel, 1974; Dynamics of connective tissue macromolecules, ed. by P. M. G. Burleigh a. A. R. Poole, Amsterdam — Oxford, 1975; Mechanisms of tissue injury with reference to rheumatoid arthritis, ed. by R. J. Perper, N. Y., 1975; Tissue protei-nases, ed. by A. J. Barrett a. J. T. Dingle, Amsterdam — L., 1971.
L. A. Lokshina.