From Big Medical Encyclopedia

MUCOPOLYSACCHARIDES — difficult connections which molecules consist of a proteinaceous component and covalently the carbohydrate chains attached to it containing a large number of the repeating disakharidny links from hexuronic acids and aminosugars; are a part of intercellular substance of the majority of types of connecting tissue of vertebrata, also hearts contain in skin, bones, synovial fluid, cartilages, joints, capsules, a vitreous and a cornea of an eye, connective tissue fibers of vessels. Together with fibers collagen (see) and elastin (see) M. form a matrix, or «the main substance», in Krom there are fibroblasts which are the main connective tissue cells synthesizing M. Biol, M.'s role is not limited only to the fact that they are «basic» the «sticking together» and «greasing» materials. These connections play an important role in processes of growth and an angenesis, fertilization and reproduction, permeability of cellular membranes and in many other processes providing normal functioning of many systems of an organism. One of representatives of this class of uglevodsoderzhashchy connections — heparin (see), has anticoagulative activity; it is in intercellular substance of many bodies — a liver, lungs, heart, arterial vessels. M cover a surface of almost all zooblasts, participating in ion exchange, immune responses, a differentiation of fabrics. Nek-ry specialized cells, napr, granulocytes or thrombocytes, contain M. in special organellas of the cytoplasm. Inherited disorders of exchange of M., in particular insufficiency of the hydrolases participating in disintegration of these connections lead to M.'s accumulation in lysosomes of cells and development of serious lysosomic illnesses of accumulation — mukopolisakharidoz (see). Change of normal exchange of M. happens not only at mukopolisakharidoza, but also at various forms of rheumatism, arthritises, hypovitaminoses. At nek-ry fiziol, and patol, states M.'s concentration in blood can change towards reduction or increase. At pregnancy, proliferation or dystrophy of fabrics, various infections, X-irradiation M.'s concentration in a blood plasma sharply increases. At nek-ry diseases of kidneys p defeats of a parenchyma of a liver M.'s concentration in blood decreases.

There are data that at the nek-ry stressful situations which are especially followed by increase in blood pressure education of the sulphated M. — a geparansulfat, a dermatansulfat and a hondroitinsulfat substantially increases in smooth muscle cells of large vessels. The aortas collecting on walls and other vessels the sulphated M. as assume, connect lipoproteids of low density of a blood plasma that promotes formation of atherosclerotic plaques.

Except interaction with lipoproteids, M. are capable to form complexes with various blood proteins: with hemoglobin, wasps - (5-and h - glo-bulinami, with components of fibrinolitic system (fibrinogen, plasminogen). A number of enzymes can suppress or activate Nek-rye M. So, heparin in model experiences activates adenylate-tsrshlazu, and collecting at a disease Gurler dermatansulfat and geparansulfat suppress activity acid (Z-B-galaktozi-dazy lysosomes (see. Gargoilizm ).

Poliani-onny properties M. are of great importance for processes of calcification of a bone tissue. M.'s removal from cuts of a cartilage leads to falloff adjournment of mineral salts in this fabric. It is experimentally shown that ability of the decalcified cartilage to connect ions of sodium, potassium, calcium, etc. is in direct dependence on the maintenance of a hondroitinsulfat. During the processing of the decalcified bone hyaluronidase (see), M. participating in degradation, inclusion 45 Ca in a bone tissue sharply decreases.

The term «mucopolysaccharides» was offered in the 30th 20 century by Maier (To. Meyer) and in the next several decades it was widely used in scientific literature. At the same time believed that M. do not contain proteins, and their small amounts found in drugs M. from various sources considered impurity. However in process of improvement of methods of preparative allocation of M. it became clear that practically in all M. there are proteinaceous components, to the Crimea the considerable number linear heteropolysaccharide-nykh of the chains which received afterwards the name of glikozaminoglikan is covalently attached.

In this regard (M. of Stacey) and S. Barker in 1960 the uglevodbelkovy connections participating in reactions, characteristic hl suggested to call Stacey mucopolysaccharides. obr. for polysaccharides. In these reactions of M. most often call just glikozaminoglikana, sometimes acid glikozaminoglikana or neutral glikozaminoglikana, pointing out by that abundance of the remains uro-new to - t in geteropolisakharidny chains of a molecule M. Mucopolysaccharides, behavior to-rykh the hl is defined. obr. a proteinaceous component of a molecule, it was offered to call mukoproteidam.

In scientific literature even more often M. is called by glikozaminoproteoglika-us or proteoglycans since these terms underline a covalent bond practically all types of glikozaminoglikan with a proteinaceous component of a molecule M., however in medical literature the term «glikozaminoglikana» continues to remain a synonym of the term «mucopolysaccharides».

Formally M. could be considered as one of versions glycoproteins (see), however basic distinctions in structure of their molecules force to distinguish these uglevodsoderzhashchy biopolymers in two various classes. The molecule of a glycoprotein consists usually of one or several carbohydrate chains, in to-rykh no more than 15 — 20 monosaccharide-nykh of the remains, and carbohydrate chains of a molecule M. contain, to-rykh there can be several tens on a molecule, are constructed of very large number of the repeating disakharidny fragments.

Depending on structure of carbohydrate chains of M. subdivide into seven main types. Six of them — hyaluronic acid (see), chondroitin-4-sulfate, chondroitin-6-sulfate (see. Chondroitinsulphuric acids ), dermatansulfat, heparin and geparansulfat — are structurally similar and contain the alternating disakharidny links consisting of the remains of the sulphated aminosugars in the polisakharidny chains and hexuronic acids (see) — D-glucuronic or L-iduronic. In the seventh type M. a carbohydrate part is presented keratansulfaty or keratosulfate, in disakharidny links to-rogo instead of hexuronic to - the t is a D-galactose. In addition to the listed seven main types of the glikozaminoglikan which are a part of a molecule M. several new types chondroitin-sulfates (D, E), dermatansulfa-that are allocated (N), the chondroitin differing in various degree of a sulfatirovannost hexuronic to - t and geksozamin.

Except the main monosakharidny components, as a part of M.'s glikozaminoglikan as minor sugars L-fukoza meet (see. Fukoza ), sialic acids (see), D-mannose (see. Mannose ) and D-xylose (see. Xylose ). The first three sugars are included into lateral branches of glikozaminoglikan, and xylose participates in formation of uglevodpeptidny communication of the majority of M.

The general structure of molecules M. can be presented on models of two types. It agrees one of them, rather small hydrophobic peptide part M. bears on itself a significant amount of polisakharidny hydrophobic chains. Such structure M. of a membrane of a lamellar complex (Golgi's device) possess. Part of molecules M. has other structure — they are extended and the peptide core, to Krom through short is the cornerstone of them (about 10 amino-acid remains) or long (apprx. 35 amino-acid remains) intervals join carbohydrate chains. Accession of glikozaminoglikan to a peptide part of a molecule M. is carried out through a so-called binding site, in Krom uglevodpeptid-ny communication mostly is carried out through the O-glycosidic linkage of D-xylose from the rest of serine of a peptide chain. Except xylose, the specific binding site contains two rests of a galactose and the rest glucuronic to - you, to a cut the repeating disakharidny fragments characteristic of polisakharidny chains M.

Mol join. the weight (weight) of M. also varies over a wide range (from 1-105 to 4-106). Such polydispersion is observed practically in all drugs M. and speaks, apparently, not only considerable fluctuations in number and length of chains of glikozaminoglikan, but also distinctions in a pier. scales of proteinaceous components M. Besides, the polidispers-nost can speak ability of molecules M. to aggregate with each other, and also with other biopolymers, in particular with proteins.

The structure of proteinaceous components M. is studied insufficiently. The amino-acid structure of M. of a cartilage of different animals can testify to similarity of their structure and to a homology of structure of proteinaceous components. However, according to a number of researchers, existence of several peptide chains in M. cannot be excluded from cartilages.

M are well dissolved in water and water-salt solutions and not dissolved in alcohol, acetone, ether and nek-ry other organic solvents. Polianionny properties M. are defined by presence at polisakharidny chains not only carboxyl (SOON-) groups hexuronic to - t, but also sulphatic groups. Biosynthesis of carbohydrate part M. is carried out by a series high-specific glikoziltrans-feraz and sulfotransferases. Hydrolases of lysosomes participate in M.'s disintegration: Glikozidaza (see. Karbogidraza ), sulphatases (see), Peptidgidrolaza (see).

Preparative allocation of M. from the fresh or dehydrated and fat-free by acetone fabrics is carried out by means of their extraction by salt solutions. For removal of a proteinaceous component the received drugs M. process the proteolytic enzymes hydrolyzing uglevodpeptidny bonds. Proteins delete with a denaturation or further enzymatic digestion, and divide mix of the formed glikozaminoglikan fractional sedimentation tsetavlony or by means of ion-exchange chromatography (see). Paper electrophoresis or on cellulose acetate belongs to the micromethods applied to assessment of degree of purity of M. (see. Electrophoresis ) in combination with immunol, methods. M.'s homogeneity in such analysis confirmed with analytical ultracentrifugation usually is considered reliable criterion of identity of M. though there can be certain difficulties in interpretation of results in of communication with polymorphism of M.

Methods of quantitative definition of the isolated M. are based by hl. obr. on specific staining reactions, to-rye give their carbohydrate components at interaction with strong to-tami during the heating: hexuronic acids decide on the help of a carbazole and ortsin, neutral sugar — an antronovy method etc.

In spite of the fact that the structure of carbohydrate components of various M. is similar, between them there are certain distinctions.

Hyaluronic acid is the only representative bore ul fatiro in annas ykh hl iko deputy Eno of hl and-kanov. Unlike other glikozaminoglikan a chain hyaluronic to - you differ in constancy of structure, branchings or any changes in structure of carbohydrate components are not characteristic of it. Other feature hyaluronic to - you are the big length of its chain. Pier. the weight (weight) hyaluronic to - you approximately by 10 times surpasses a pier. weight (weight) of other glikozaminoglikan. Owing to the high hydrophily hyaluronic to - that connects intersticial water in intercellular spaces that promotes sharp increase in counteraction of fabrics to compression.

Existence hyaluronic to - you in synovial fluid cause its high structural viscosity therefore joints are capable to maintain big loading. In fabrics and liquids hyaluronic to - that exists, apparently, in a complex with this or that protein, the quantity to-rogo is usually small (to 2%) and, according to different researchers, varies depending on a source and methods of receiving hyaluronic to - you. In spite of the fact that a covalent bond hyaluronic to - you with protein are proved in some cases by means of enough thin methods, the chemical nature of this communication is not found out.

Hondroitinsulfata in comparison with other M. are most widespread in a human body and animals. They are subdivided into chondroitin-4-sulfate (hondroitinsulfat And), chondroitin-6-sulfate (hondroitinsulfat C) and dermatansulfat (hondroitinsulfat In). Polisakharidny chains of two isomeric hondroitinsulfat — hondroitin-4-and chondroitin-6-sulfa-tov — contain in quality of the repeating link the disaccharide representing> O-p-D-glyukurono-zil-(1 — 3) - | 3-0-atsetilgalaktozamin. At the same time chondroitin-4-sulfate is sulphated at the fourth carbon atom (With *), and hondro-itin-6-sulfate — at C6 atom of N-atsetilgalaktozamina. Each polisakharidny chain both chondroitin - • eulfat contains from 30 to 50

disakharidny fragments. It should be noted that extent of sulphation of polisakharidny chains of hondroitinsulfat can vary. Heterogeneity of polisakharidny chains is shown that a small part of disakharidny fragments of hondroitinsulfat in general can be not sulphated, and in other certain sites of a polisakharidny chain not only the remains N-atsetilga-laktozamina, but also glucuronic to - you are sulphated. At last, structural heterogeneity is shown that there are hybrid molecules of hondroitinsulfat containing in the polisakharidny chains the remains of N-atsetilgalaktozamina sulphated both at C4, and at Saturday. Extent of sulphation varies as in drugs of the hondroitinsulfat allocated from one source and in the drugs emitted from different sources. Isomeric forms hondroitin-4-and chondroitins-6-sulfates can be present at fabric independently from each other or at mix with each other. The majority of drugs of hondroitinsulfat differs in polydispersion. Pier. the weight (weight) of hondroitinsulfat fluctuates between 10 Ltd companies and 60 000. In cartilages and tissue of arteries hondroitin-4-and hondro-itin-@-sulfates are connected to a specific proteinaceous kor. The proteinaceous component makes apprx. 17 — 22% of all mass of a molecule hondroitinsul a fatprotein.

Dermatansulfat (hondroitinsulfat In) is isomer of hondroitinsulfat, in Krom instead of the remains D-glucuronic to - you there are remains L-iduronic to - you, connected and-1 — >3 communication with sulphated usually at C4 N-atsetilga-laktozaminom. Such repeating disakharidny fragments are connected with each other [5-1-^4-связями. Except the drugs, typical for a dermatansulfat, containing only the remains L-iduronic to - you, drugs are received, in to-rykh there is a nek-swarm a quantity D-glucuronic to - you; dermatansulfat from tissue of an aorta of a horse along with typical disaccharide-nymi fragments contains fragments of a hondroitinsulfat and chondroitin-6-sulfate in the molecule. On the properties dermatansulfat it is similar to other hondroitinsul-veils, however unlike a hondroitinsulfat And it has properties of anticoagulant. Pier. the weight (weight) of a dermatansulfat fluctuates depending on a source and a way of receiving and is on average equal to 23 000.

Keratansulfat, or keratosulfate, differs from other M. in what its disakharidny links do not contain uranium to - t. The Polisakharidny chain of a keratansulfat consists of the alternating disakharidny fragments consisting of the remains of a D-galactose and 6-sulfata-] the Ch-atsetil-glyukozamina, connected among themselves R-1-^4-связью. Disakharidny fragments are connected | >by 3-1 — 3-communication. The remains of a galactose in a keratansul-veil can be also sulphated. Besides, in polisakharidny chains of a keratansulfat there are remains of a fukoza, mannose, sialine to - t and N-atsetilgalaktozamina, situation to-rykh in a chain so far it is definitely not known. There are data that communication with a proteinaceous component in a ke-ratansulfata from a cornea is carried out by means of glinyuzilamidny communication between the remains of a glycosamine and asparagine, and in a keratansulfata from a cartilage — by means of Au-glyco-zidnoy of communication between the remains of N-atsetilgalaktozamina and ON-group-poy the rest of serine or threonine.

Heparin and geparansulfat have very similar structure with other types of glikozaminoglikan, but differ from them on localization and function in animal fabrics. In connecting fabric heparin meets not as a structural component, and as an intracellular component mast cells (see). Heparin is found in skin, in tissues of lungs, a liver, a mucous membrane of a stomach. Was considered that the repeating disakharidny fragments of heparin consist from [>(1 — 4) - r - D - glyukuronozil - >(1 — 4)] - a - D - N-atse-tilglyukozamina. However detection in heparin of the remains L-iduronic to - you, and also | 3 bonds D-glucuronic to - you (fragments of heparin of races shcheplyalis a r-glucuronide-zoy) allowed to present carbohydrate structure of this biopolymer in the form of the repeating tetrasakharid-ny fragment. Such tetrasakharid it is possible to consider as two connected and-1 — >4 communication of disaccharide, containing in the structure L-iduro-new (sulphated at C2) and D-glucuronic to - you, connected with the remains of N-atsetilglyukozamina sulphated at C2 and Saturday respectively. Geparansulfat consists, apparently, of the same fragments with a large number N-acetyl both the smaller number of N-sulfate groups and low extent of O-sulphation.

Histochemical methods of definition of mucopolysaccharides in fabrics. Success of identification of M. in fabrics considerably is defined by way of fixing of fabrics. The best way of fixing of fabrics for gistokhy, M.'s definitions is freeze drying (see. Lyophilizing ). In gistol, practice as the universal fixer of carbohydrate connections 10% solution of neutral formalin are widely used (according to Lilly). This fixer provides a possibility of the indicative analysis of M. at good safety of structures of the fixed fabric. For fuller sedimentation of M. add ethanol, lead salts, barium hydroxide to solution of formalin. 96% alcohol or liquid Carnoy are applied to neutral M.' fixing. For preservation in readily soluble M.' fabrics ways of fixing using dioxane, mix of tetrahydrofuran with acetone, solution of cyanuric chloride in methyl alcohol, etc. are offered.

The majority of methods gistokhy, M.'s definitions are group since serve for detection of connections with identical or similar reactionary groups. Therefore separate M.' identification demands carrying out chemical or enzymatic control, and in some cases — uses of duplicative methods.

By the group method which is the cornerstone gistokhy, definitions of carbohydrate connections, is CHIC reaction (see), based on selective oxidation iodic to - that 1,2-glikolny groups of carbohydrates to aldehydes, to-rye in reaction with fuk-sinsernisty to - that form connection of crimson color. CHIC - hollow zhitelnuyu the glycogen and neutral M. give reaction, to-rye can be in a complex with proteins. The structures containing acid M. in fabric cuts do not react with fuksinser-nisty to - that. At statement CHIC reaction after filling of pieces of fabric in paraffin disappears need to differentiate neutral M. with the lipids dissolved during the conducting of cuts, presence of a glycogen is excluded by fermental control with amylase.

A specific method gistokhy, acid M.' definitions is metachromatic coloring by their tiazinovy dyes, to-rye change the color towards a red range (with the advent of violet, lilac tones) at interaction with the structures arranged poly-anionnymi. The chemical components of fabrics giving metachromatic coloring received the name of hromotropny substances: from here expressions «hromotropny substance», «hromotropny hypostasis» that means presence at fabric substrate of the acid M. giving metachromasia (see). The phenomenon of a metachromasia appears in the presence of the active dissociated acid groups, carboxyl or sulphatic therefore identification of the connections giving metachromatic coloring is carried out at various pH values of the painting solution. The metachromasia of the structures containing hyaluronic to - that, comes to light at pH 4,0 above; sialine to - you give a metachromasia at pH from 2,0 to 3,0; the metakhromatichesk sulphated by M. are painted at lower pH values (from 0,5 to 1,5).

Treat group methods of definition of acid M. also Hale's method of N coloring by alcian blue. Hale's method is based on linkng of colloid ferric hydroxide by acid M. with the subsequent identification of its localization by training of Prussian blue. This method in a combination about CHIC reaction allows to differentiate accurately neutral and acid M. and to reveal acid M. and CHIC-positive structures at the same time on one cut. Alcian blue, relating to phthalocyanine, interacts with carboxyl and sulphatic groups of acid M., forming with them complexes, it is similar other basic to dyes (see). The sulphated M. of nek-ry fabric structures poorly are painted alcian blue, and the soft methylation deleting sulphatic groups strengthens an altsianofiliya, apparently, due to the best access of dye to carboxyl groups of substrate.

For differentiation of the sulphated M. and sialoglikozamino-proteoglycans use a method of methylation, at Krom carboxyl groups are blocked, and sulphatic are removed; at the subsequent demethylation there is a recovery of carboxyl groups. Thus, methylation — demethylation can be used as selective desulphonation of acid M.

Identification of the separate hromotropny substances revealed by all these methods is carried out by means of pretreatment of fabric cuts by the corresponding enzymes: hyaluronidases and nep-raminidazy. Need of carrying out differential gistokhy, M.'s analysis is dictated by the fact that hro-motropny structures, as a rule, represent complex multi-component systems of various carbohydrate connections, definition to-rykh is necessary for deeper understanding of essence fiziol, and patol, processes.

Bibliography: S. M. and Zakharov M. M. bull-calves. New data on glikozamino-glycanes and proteoglycans, Vopr. medical chemistry, t. 25, No. 3, page 227, 1979, bibliogr.; Vidershayn G. Ya. Biochemical bases of glikozidoz, page 12, M., 1980; Dishe 3. Staining reactions of carbohydrates, in book: Methods of chemistry of carbohydrates, the lane with English, under the editorship of N. K. Kochetkov, page 20, M., 1967; Pearce E. A histochemistry, the lane with English, page 207, M., 1962; The Principles and methods of gisto-cytochemical analysis in pathology, under. an edition of A. P. Avtsyn, etc., page 15, M. — L., 1971; Stepanenko B. N. Chemistry and biochemistry of carbohydrates (polysaccharides), page 161, M., 1978; In of i in the expert about m b e J. S.j a. W e b er J-M. Muco-polisaccharides, Amsterdam, 1964; Complex carbohydrates of nervous tissue, ed by R. U. Margolis a. R. K. Margolis, 34., Y. — L, 1979; Dorfman A. Adventures in viscous solutions, Mol. Cell. Biochem., v. 4, p. 45, 1974, bibliogr.; Kimata K. o. Cytodifferentiation and proteoglycan biosynthesis, ibid., v. 1, p., 21 1, 1973, bibliogr.; Lindahl U. Hook l’ Glycosaminoglycans their and binding to biological macromolecules, Ann. Rev. Bio-Chem., v. 47, p. 385, 1978, bibliogr *

McKusick V. A., Heritable disorders of connective tissue, St Louis, 19 72-McManus J. F. A. a. M o w r y R. w’ Staining methods, N. Y., 1960.

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