LYSOSOMES (grech, lysis decomposition, easing + soma a body) — the specialized cytoplasmatic membrane structures forming vacuolar system of a cell various by the sizes and density, characteristic property to-rykh is the content of hydrolases in high concentration. L. perform a large number of various functions in an organism. Uniform process of an enzymatic depolymerization of substrates enzymes L is the cornerstone of these functions. Participation of L belongs to the functions connected with heterophagocytosis. in the course of cellular food, in a lysis of microorganisms and viruses (protective function), in intracellular digestion of biopolymers, in an initial stage of an immunogenesis and an autoimmunogenez, in biosynthesis of biologically active agents, in extracellular hydrolysis of biopolymers (see. Phagocytosis ). Participation of L belongs to the functions connected with autofagotsitozy. in a refining process of a cell from lost funkts, value of structures and macromolecules, in processes of embryonic and post-natal development (cellular differentiation, metamorphoses, regression, involution, an atresia), in regulation of intensity of secretion (krinofagiya), in utilization of excess of the feedstuffs accumulated in a cell, in endogenous food at deficit of feedstuffs (reconstructive function). It is important that at unicells functions L prevail., connected with geterofagichesky processes, and in process of evolutionary development value of autofagichesky processes gradually increases in cells of advanced organisms. In nek-ry types of cells of L. perform strictly specialized functions. So, e.g., L. spermatozoa are responsible for process of an invasion and fertilization.
L. were for the first time described in work C. de Duva and sotr. in 1955, to-rye found group of hydrolases (see. Hydrolases ) in the light mitochondrial distillate allocated by means of differential centrifuging from homogenate of a liver of a rat. It was established that these enzymes contain in special type of cytoplasmic particles to dia. 0,1 — 3 microns, to-rye were also called lysosomes. After C. de Duv and sotr. noted that hydrolases L. show the activity only if particles were damaged previously — or mechanically, or by osmotic shock, freezing — thawing or at effect of detergent.
Opening C. de Duva was prepared tsitol. I. I. Mechnikov's researches, to-ry predicted existence of L. also described them funkts, property as the main alimentary system cells (see).
L. are found almost in all types vegetable and zooblasts of both one-celled, and advanced organisms. It testifies to their extreme all-biological importance. Allocate three basic groups of the structures relating to L.: prelizosoma (primary lysosomes), actually L. and post-lysosomes (fig. 1 — 3).
To prelizosomakhm the heterophagosomas (they are phagosomas, fagotsitozny, or pinotsitozny, vacuoles) which are formed by endocytosis (belong see. Pinotsitoz ), and autofagosoma (autofagiruyushchy or autolytic vacuoles) which are formed in the course of an autofagotsitoz. In a pra lysosomes there are substrates which are subject to digestion, but prelizosoma do not contain hydrolases.
Actually L. subdivide on primary and secondary. Primary L. (they are protolysosomes, granules of accumulation, dense little bodies) represent the structures with a homogeneous matrix delimited by a single lipoproteidny membrane (see. Membranes biological ). They contain only again synthesized hydrolases and actually are storages of hydrolases. Secondary L., the prelizosomam which are formed by merge of primary H.p. or other components of vacuolar system, contain both hydrolases, and the substances which are subject to hydrolytic decomposition (digestion). These L. happen two types: autofagichesky (autofagolizosoma, cytolysosomes, cytolysosomes, etc.) and geterofagichesky (heterophagolysosomes, phagolysosomes).
The vakuolepodobny structures containing only the remains of undigested material treat post-lysosomes (residual little bodies, miyelinopodobny figures, etc.).
V L. it is localized apprx. 60 various hydrolases, the majority from to-rykh are most active at acid reaction of the environment. L. undergo the dynamic changes throughout a life cycle which are expressed in continuous interaction (merge and division) of various types L., than heterogeneity of population of these cytoplasmatic structures also speaks. There are data not only about morfol, distinctions of L., defined by their contents, but also about qualitatively different set of enzymes in L. from the same fabric. Substrates for lysosomic hydrolases are all complex substances and biopolymers of an organism, including a squirrel, nucleinic to - you, polysaccharides, triglycerides etc. L. contain also karbogidraza (see).
Enzymes L. are synthesized on ribosomes of a cytoplasmic reticulum and are transported in a zone of the lamellar device (see. Golgi complex ), where there is a final formation specific to L. a set of enzymes and their packaging in a membrane framework. The created primary L. gemmate from structures of the lamellar device from its concave surface. In nek-ry types of cells primary L. are formed in the sites of a cytoplasmic reticulum localized near the lamellar device. For L. the complex fermental organization is characteristic. A number of specialized hydrolases is built in a membrane of L., where they perform function of the peculiar receptors learning the material which is subject to digestion and the biopolymers initiating process of ekstralizosomny splitting that is necessary for formation of secondary L.
Normal functioning of L. depends on a condition of their membranes. Membranes of L. are easily permeable for low-molecular weight compounds [about a pier. it is powerful (weighing) below 240], napr, for products of intra lysosomic splitting of biopolymers. Permeability of membranes of L. it is regulated by nervous and hormonal systems. Cyclic 3', 5' - AMF and its analogs (dibutyryl - cyclic AMF, 8-methylthio-cyclic AMF), and also the factors stimulating synthesis and accumulation in cells cyclic 3', 5' - AMF (E1, E2 prostaglandins, E2a etc., beta and adrenergic catecholamines, a histamine, inhibitors of phosphodiesterase), have stabilizing action on membranes of L. At the same time the factors reducing concentration endogenous cyclic 3', 5' - AMF (e.g., inhibitors of adenylatecyclase), strengthen action of the agents destabilizing membranes of L. Sharp disturbance of stability of membranes of L. cause cyclic 3', 5 '-guanozinmonofosfat (GMF), its analogs and agents, the promoting accumulations of cyclic GMF in cells (cholinergic substances). Permeability of membranes of L. physical can change considerably under the influence of various. influences (radiation by UF-light, x-ray and gamma-rays, action by ultrasound) and chemical connections (nek-ry hormones, fat-soluble vitamins, medicines).
Pathology of lysosomes
the Universal role, to-ruyu play L. in life activity of a complete organism and separate cells, predetermines their value in development numerous patol, processes. However in one cases of damage of L. happen primary and are releasers in development patol, reactions, in others — involvement of L. in patol, process has secondary character.
The hereditary diseases connected with disturbance of synthesis of separate enzymes L belong to primary patol, processes, first., conducting to patol, to accumulation in L. substances, missing enzyme is necessary for splitting to-rykh (see. Hereditary diseases ), and, secondly, patol, the states connected with selective damage of membranes of L.
Inborn lysosomic diseases of accumulation are a consequence of primary genovariation, shown either the full blocking of synthesis of fermental protein, or synthesis of the proteinaceous molecules having sharply reduced bio-kata lytic activity. Various belong to diseases of accumulation glikozidoza (see), a syndrome the Cudgel — Johnson (see. Hepatoses ) and other diseases. With insufficiency of separate enzymes L. connect development of atherosclerosis (insufficiency cholesterol-esterase of unstriated muscles of cells of arteries — KF 188.8.131.52) and obesity (insufficiency of a lipolytic complex of adipocytes).
The special group is made patol, the states connected with selective damage of membranes by L. Lizosomotropny by action SiO possesses, e.g. 2 , to-ry, collecting in L. alveolar macrophages, mechanically damages their membranes, causes release of active hydrolases and the subsequent death of cells. Death of coniophages is the starting moment in development of a silicosis. At the same time from coniophages the fibrogenny factor inducing fibroblasts to the strengthened synthetic activity is released and comes to the environment. It is not excluded that this factor is lysolecithin, to-rogo lysosomic membranes are a source. Lysolecithin collects in coniophages thanks to decrease in them under the influence of SiO 2 activities of a lizoletsitinaza (see. Lecithinases ).
In the expressed L damaging membranes. nek-ry mycotoxins, phospholipases, activators and products of peroxide oxidation possess action. Are suggested that the disturbances of stability of membranes of L caused by various cancerogenic agents. (solubilization of hydrolases, damage of chromosomes) are the cornerstone of malignant transformation of cells. However against this concept there are serious objections though participation of L. in mechanisms of carcinogenesis, a progression of tumors, interaction of a tumor and an organism, development of a cachexia, in implementation of chemotherapeutic effect and beam treatment it is established experimentally.
Participation of L can be taken for granted. in inflammatory and degenerative processes. In development inflammations (see) the important role belongs to L. thrombocytes and polymorphonuclear leukocytes. L. are the main weapon of an organism in its fight against pathogenic bacteriums and viruses. Nek-ry microorganisms are capable to inhibit or supressirovat influence of L., avoiding thereby effect of hydrolytic lysosomic enzymes. Treat such microorganisms, e.g., a tubercular stick, from a cut the sulphated glycolipid responsible for similar suppression is emitted.
With activity of L. are connected and immunol. processes. The damaging action of a complex antigen — an antibody on cells can be stopped by destruction of this complex L. e.g., in eosinophils, to-rye collect at allergic states. On the contrary, adjournment of a complex antigen — an antibody in the places unavailable to effect of lysosomic enzymes, is a basis of a pathogeny of damages of various character up to development of a glomerulonephritis, necrotic arthritises, an acute endocarditis, Artyus's phenomenon etc.
L. take active part in elimination of critical conditions at traumatic damages and a burn disease, carrying out processes of fermental cleaning of wounds of nekrotizirovanny fragments of fabrics.
Disturbance of integrity of membranes of L. secondary character it is observed at a hypoxia, disturbance of acid-base equilibrium, after injuries and operative measures, at starvation and proteinaceous insufficiency, shock, changes of the hormonal status of an organism, at arthritises of various etiology, etc.
Diagnosis of lysosomic diseases is carried out by definition of activity of specific lysosomic enzymes in blood serum and urine. Increase in activity of such enzymes demonstrates disturbance of stability of membranes of L. Specific diagnosis of hereditary lysosomic diseases is directed to detection of fermental defect by definition of activity of a wide range of hydrolases in such types of cells as leukocytes, fibroblasts of skin, a cell of an amniotic fluid and so forth. Big a wedge, prenatal diagnosis of these diseases matters.
Perspective approach to treatment of lysosomic hereditary diseases is introduction to an organism of missing enzymes in the form of liposomes, to-rye come to cells by heterophagocytosis and, merging with L., deliver enzymes to the place of their direct action.
Implementation to lay down. actions of a number of pharmaceuticals it is carried out through L., hl. obr. by selective change of permeability of their membranes. So glucocorticoids at inflammatory reactions work, e.g., salicylates at rheumatism, streptomycin at infections and so forth.
Bibliography: I. I. swordsmen. Lectures about comparative pathology of an inflammation, SPb., 1892; Pokrovsky A. A. and Tutelyan V. A. Lysosomes, M., 1976, bibliogr.; De D u v e C. and. lake of Tissue fractionation studies, Biochem. J., v. 60, p. 604, 1955; H o 1 t z m a n E. Lysosomes, Wien — N. Y., 1976, bibliogr.; Lysosomes and storage diseases, ed. by H. G. Hers a. J. van Hoff, N. Y., 1973; Lysosomes in biology and pathology, ed. by J. T. Dingle a. o., v. 1 — 4, Amsterdam — L., 1969 — 1975.
B. A. Tutelyan; H. T. Raykhlin (stalemate.).