From Big Medical Encyclopedia

GLYCOGEN (grech, glykys sweet + gennao to create, make; synonym animal starch) — the main reserve polysaccharide of the highest animals and the person constructed of α-D-glyukoza's remains (C 6 H 10 O 5 ) n . It is opened by K. Bernard in 1857. Contains in all bodies and tissues of animals and the person, in the greatest number in a liver (to 20%) and muscles (to 4%), meets also in some plants, the highest mushrooms, microorganisms (e.g., yeast). The inborn hereditary diseases connected with disturbance of exchange of carbohydrates in a considerable part are presented by glycogenoses.

Sizes pier. the weight (weight) of native G. are in limits 107 — 10^9 above. Various G. geterodispersna, i.e. represent mixes of molecules of different weight. Size pier. G.'s weight depends on a species of an animal, body, fiziol, states and on a method of allocation of. From fabrics G. it is possible to allocate with extraction of cold 10% trichloroacetic to - that with the subsequent sedimentation by alcohol (Ostern's method) or extraction of fabrics we heat 60% solution caustic heat, the considerable depolymerization of its molecules occurs G. hydrolyzing proteins and other connections, but generally keeping which then is besieged alcohol (Pflyuger's method), however at G.'s allocation by these methods, and for receiving more native drugs use extraction by a cold water or phenol, homogenization of fabrics in glycine buffer pH 10,4 solution with chloroform with the subsequent differential centrifuging.

At animals the constant picture of distribution of G. on a pier remains. to scales, having, apparently, individual character and a little changing as at G.'s decrease (e.g., at starvation or administration of adrenaline), and at stimulation of biosynthesis of G. (e.g., at administration of glucose). Obviously, it is reached by steady regulation of metabolism of. At patol, conditions a pier. G.'s weight can strongly change.

Represents the amorphous white powder which is dissolved in water with formation of opalescent or milky-white solutions. G.'s solubility is equal to 15 — 21% at 20 °. From solutions G. it is besieged by alcohol, tannin and ammonium sulfate at full saturation. With solution of iodine G. depending on an origin of drug gives coloring from red to yellow-brown, a cut disappears at boiling and again appears during the cooling. Has optical activity, [a] D + 196 °. Since in a huge molecule G. there is only one hemiacetal hydroxyl, G. has the insignificant recovering (reducing) ability. Each glucose unit contains on average 3 alcoholic hydroxyls (from 2 to 4) therefore at effect of methylating agents on G. it is possible to receive trimetilglikogen.

G.'s boiling with diluted to-tami leads to its incomplete hydrolysis and education dextrins (see). A product of full hydrolysis of G. is glucose (see):

(C 6 H 10 O 5 ) n + nH 2 >O — nC 6 H 12 O 6 .

Full hydrolysis of G. with quantitative definition of the formed glucose is one of ways of quantitative definition of.

Fig. 1. The scheme of a structure of a molecule of a glycogen according to Maier: and — a structure of the site of a molecule of a glycogen (* — branching points); — the site of a molecule of a glycogen; white circles — the remains of glucose connected α-1,4-svyazyyu; black circles — the remains of glucose attached α-by 1,6 communication; R — the reducing endgroup (internal circuits or branches — sites between branching points; outside chains or branches begin from branching points and come to an end in not reducing rest of glucose).

Molecules G. are constructed of dichotomizing branching polyglucosidic chains in which glucose units are connected alpha 1,4 - glucosidic bonds; in branching points are available alpha 1,6 - glucosidic bonds (7 — 9%) (fig. 1, a).

In a molecule G. distinguish internal circuits (branches) — sites of polyglucosidic chains between branching points and outside chains (branches) — sites from peripheral branching points till not reducing end of a chain (fig. 1,6). Length of outside and internal circuits in molecules G. considerably varies depending on a species of an animal and body, from to-rogo is allocated. This scheme of a structure of a molecule G. was offered by Maier (K. N. to Meyer) and Bernfeld (R. Bernfeld) and was generally recognized since was confirmed not only chemical, but also euzymatic researches.

Fig. 2. The scheme of a structure of a molecule of a glycogen according to Whelan: And, In and With — branches (chain) of a molecule of a glycogen. And — the site of a chain from the closing not reducing balance to the next branching points which is not bearing on itself other branches; In — the chain having the closing not reducing balance and bearing on itself other chains (And or In); With — the only chain having the reducing trailer rest.

High pier. G.'s weight and results of hydrolytic decomposition of various G. gave the chance to W. Whelan and his employees in 1970 to offer new version of the scheme of a structure of a molecule G. (fig. 2). Total number of A-chains both in Maier's scheme, and in W. Whelan's scheme also approximately equally in number of B-chains. On the scheme the «hidden» chains are visible In, to the Crimea the «hidden» A. V chains of this model a half of chains can be attached In bears twice bigger number of chains And; the second half of chains In does not bear chains And, but bears chains of Century. W. Whelan's scheme does not express precisely original structure of G., but explains some new data obtained in chemistry of glycogens.

Fig. 3. The diffraction pattern of a muscle of an ascarid (shooters specified the postponed chastichkovy glycogen).

In 1942 A. A. Lazarev by differential centrifuging allocated the high-molecular G. called chastichkovy from a liver. In the sixties 20 century were received electronic and microscopic pictures of chastichkovy G. (fig. 3). The most coarse particles having an appearance of mulberry berries (to dia. 50 — 200 nanometers, pier. weight 10 7 — 10 9 ), the smallest were called alpha particles, being their sub-particles (to dia. 20 — 40 nanometers, pier. weight 2 — 5×10 6 ) — gamma particles, and intermediate in size, consisting of a small number of gamma particles — beta particles.

From 40th years 20 century were considered that Mother compound in G.'s biosynthesis is glyukozo-1-phosphate, the glucose unit to-rogo is transferred to an acceptor — a glycogen priming under the influence of specific phosphorylase:

(C 6 H 10 O 5 ) n + With 6 H 11 O 5 OPO 3 H 2 <-> (C 6 H 10 O 5 ) n+1 + H 3 PO 4 .

The formed linear polyglucosidic chains turn in branchy by means of an alpha glyukanvetvyashchey of glucosyltransferase (KF

Carried out for the first time owls. researchers studying of a structure of the synthetic G. received by in vitro by means of enzymes from muscles showed their proximity to natural G. (B. N. Stepanenko and sotr.). Then it was established that in vivo the main way of biosynthesis of G. is its synthesis from nukleoziddifosfatsakhar from which it is most active in this respect an uridindifosfatglyukoz (UDFG). The glucose unit of UDFG under the influence of enzyme the UDFG-glycogen — glucosyltransferase (KF is transferred to polysaccharide — an acceptor:

(C 6 H 10 O 5 ) n + UDFG -> (C 6 H 10 O 5 ) n+1 + UDF.

Further vetvyashchy enzyme turns linear chains of polysaccharide into branchy. G.'s synthesis from UDFG considers most of researchers the main thing. From the thermodynamic point of view of UDFG is much more favorable donator of glucose units, than glyukozo-1-phosphate since possesses considerably a large supply of energy, however there are data that synthesis under certain conditions can come from glyukozo-1-phosphate also in vivo.

In 1975 Mr. Krisman and Barengo (Page R. Krisman, R. Barengo) established that for lack of a glycogen priming G.'s synthesis is carried out on a molecule of protein matrix («primer») with the participation of enzyme — the initiator of synthesis of G. catalyzing transfer on protein matrix of glucose units with UDFG with formation of an oligosakharidny chain. Further process is entered by the enzyme of a glikogensintetaz operating normally.

G.'s splitting — a glycogenolysis can be carried out in the fosforilitichesky way (at effect of phosphorylase) and hydrolytic — an amylolytic way. G.'s amylolysis is carried out with the assistance of three amylases (see). alpha amylase (KF catalyzes hydrolysis of a molecule G. on large blocks which serve as a priming at synthesis of new molecules G.; beta amylase (KF hydrolyzes alpha 1,4 - bonds, consistently chipping off fragments from

the tissues of the person which are not reducing the ends of chains of G. V and animals the Soviet biochemists E. L. Rosenfeld and I. A. Popova the gamma amylase catalyzing eliminating of the remains of glucose from a molecule G. on alpha 1,4 - communication is found. The glucose released thus comes to a blood stream and is used for power needs of an organism. The main enzyme splitting G. of in vivo is a glikogenfosforilaz (KF

However completely the molecule G. can be split only with the participation of several enzymes. Phosphorylase (see) chips off glucose units, beginning from the peripheral end of outside branches of a molecule G, At approach to alpha 1,6 - to bonds its action stops. The glucose unit connected to other part of a molecule alpha 1,6 - communication, remains naked. Such rest is affected by amilo-1,6-glucosidase (dextrin-1,6-glucosidase; KF; after its removal the glikogenfosforilaza will continue the action.

The product of a phosphorolysis of G. — glyukozo-1-phosphate is isomerized under the influence of phosphoglucomutase (KF, turning into glyukozo-6-phosphate. The last can participate further in different types of exchange (glycolysis or a pentozofosfatny way); in a liver its considerable part is hydrolyzed glyukozo-6-fos-fatazoy with formation of free glucose, edges comes to blood, is and there is one of the main metabolic sources of glucose in blood.

Regulation of metabolism of G. is carried out in the neurohumoral way, its molecular mechanisms are substantially found out. One of philosophy of these mechanisms is existence of two forms of the major enzymes of metabolism of G. — a glikogenfosforilaza (phosphorylase and) and glikogensintetaza (the UDFG-glycogen — glucosyltransferase); one of these forms has a little changing activity whereas activity another is capable to change strongly under the influence of activators.

Long ago the phenomenon of bystry splitting of G. at action is known adrenaline (see). G.'s synthesis by adrenaline is oppressed. Insulin (see) — the antagonist of adrenaline, has opposite effect on G.'s biosynthesis. Other hormones — glucagon (see), sex hormones (see) etc. also influence metabolism of.

At neurogenic regulation of biosynthesis of G. ions of Sa 2+ , the muscles which are released at reduction, and a specific «proteinaceous factor» cause formation of an active kinase of phosphorylase b, and the last causes transformation of phosphorylase b into an active form — phosphorylase and.

At disturbances of exchange of G. leading to its abnormal accumulation in cells and increase in concentration of F. in blood, the so-called glycogenous (glikogenovy) disease develops, or glycogenoses (see). Depending on localization of abnormal accumulation of G. distinguish a hepatic, muscular and generalized form of glycogenoses. Classification of glycogenoses is based on total absence or deficit of this or that enzyme participating in G. Izvestno's exchange more than 10 types of glycogenoses. At hepatitises of various etiology G.'s number in blood decreases.

Methods of definition of a glycogen

In blood of the person determine G.'s maintenance by a method Preobrazhenskiy which is based on acid hydrolysis of G. besieged from blood by alkali and ethanol, and quantitative definition of the formed glucose.

G.'s number, on Preobrazhenskiy, is equal in blood of the healthy person to 2,72 mg of % (from 1,69 to 3,87 mg of %).

In blood of the person determine also by Pflayderer's method. In this case the glucose formed G. after acid hydrolysis is phosphorylated at the expense of ATP with participation hexokinase (see) therefore equimolar quantities of ADF are formed; ADF perefosforilirutsya with fosfoyenolpiruvaty with the participation of a pyruvatekinase, the formed pyruvate is recovered with the participation of NAD-N and a lactate dehydrogenase to milk to - you. The amount of glucose is found on the change of quantity of NAD-N defined spektrofotometrichesk at 340 or 366 nanometers.

Histochemical methods of definition of a glycogen in fabrics

For identification gistokhy, use methods G. in fabrics its property not to be dissolved in alcohols. Very often for fixing use absolute alcohol or liquid Carnoy. Across Neykirkh (P. Neukirch), material is fixed in the liquids sated with a dextrose; on F. L. de Gendre, apply mix of alcohol, picric, acetic to - t and formalin. The technique of Gels (J. Gelei) provides use of mix osmic to - you with absolute alcohol.

Histochemical the glycogen is defined by Best's method, Shabadash's method and PAS reaction (see. Besta method , Shabadasha ways , CHIC reaction ).

In living cell G. it is partially distributed in cytoplasm diffuzno, partially connected with granules (e.g., in eosinophilic granulocytes). At effect of the corresponding fixing liquids G. it is besieged in the form of grains and glybok. After death or in the bodies taken from an organism, G. quickly begins to disappear and the quicker, than surrounding temperature is higher. Under the influence of water G.'s dissolution strongly accelerates. Also 15% solution caustic have strong solvent action heat or muriatic pepsinony Material for preparation of the drugs intended for a research on G. shall be fixed in a fresh state. It is necessary to avoid contact it with water, fiziol, solution both to, and after fixing. The general for operation of all fixers G. is that in outside zones of drug, especially in the cells rich with protoplasm, there is a characteristic shift of a granular or glybchaty deposit of G., so-called flight of a glycogen from alcohol.

In an uncolored state cellular G. differs in strong gloss and lack of structure; it usually has an appearance of the grains located in bigger or smaller quantity in protoplasm, and at patol, conditions is frequent also in kernels of cells.

At the diseases which are followed by disturbances of carbohydrate metabolism the increased deposits of granules of G. in muscles, a liver, kidneys are observed. G.'s accumulation in an epithelium of Henle's loops at a diabetes mellitus is characteristic (see. diabetes mellitus ), connected with disturbance of a reabsorption of glucose in the conditions of a hyperglycemia. Distinguish: «stable» G. which strongly is a part of cellular protoplasm is not exposed to considerable quantitative fluctuations, often only hardly it is found (or it is not found at all) microchemical reactions, and «labile», or «account», G. which is temporarily postponed in a cell it is easy from it chipping off in process of the need of an organism for power material, subject to sharp quantitative fluctuations and clearly defined microchemical. Stable G. at fiziol. conditions is available for the person in all bodies, except a nervous system, chest gland and bones. Its constant presence at those fabric elements which are in nek-rum a distance from blood current, in cartilaginous cells and in different types of a multilayer epithelium is characteristic. G. of fabric of an embryo are rich, at to-rogo under normal conditions G. meets everywhere, except a nervous system. The increased contents it at an embryo contacts most of researchers especially brisk metabolism in the growing cells.

Sometimes G.'s presence depends on a functional condition of body. So, in an epithelium of a mucous membrane of a uterus immediately after the menstrual period the smallest maintenance of G. or even its total absence is found. To the main depots of labile G. serve a liver and skeletal muscles; at the same time in a liver G.'s disappearance at the starving animal begins with the periphery of a segment and gradually extends towards the center. Accumulation at the resumed feeding goes upside-down, i.e. from the cells located about the central veins to the periphery. Sometimes G. can be met also out of cells (in interstitial substance, limf, spaces etc.). Most often it is result of its posthumous washing away from cellular protoplasm, is more rare — an effect of intravital damage or death of cells.

The provided data on localization and dynamics of accumulation of G. in fabrics received by hl. obr. by means of a histochemistry, considerably extended in connection with development of methods submicroscopy (see) and electronic histochemistry (see). By means of a submicroscopy it was established that G. is characterized by three levels of the organization, to each of which the specific sizes and morfol are inherent, to feature (alpha, beta and gamma particles).

G.'s granules are localized in tubules and bubbles of a cytoplasmic reticulum, granular deposits of G. are found also in a matrix of mitochondrions.

Bibliography: Biochemical methods of a research in clinic, under the editorship of A. A. Pokrovsky, page 228, M., 1969; M and l of e r G. R. and Kordes Yu. G. Fundamentals of biological chemistry, the lane with English, M., 1970; Stepanenko B. N. Carbohydrates, Progress in studying of a structure and metabolism, Results of Science series, M., 1968; Stepanenko B. N. and Bobrov L. N. Modern representations about micro and macro-molecular structure of a glycogen, Usp. biol, chemical, t. 15, page 195, 1974, bibliogr.; With about of i G. T. Glycogen structure and enzyme deficiencies in glycogen-storage disease, Harvey Lect., ser. 48, p. 145, 1954, bibliogr.; K r i s m a n C. R. a. Barengo R. Aprecursor of glycogen, biosynthesis, Europ. j. Biochem., v. 52, p. 117, 1975, bibliogr.; R at m a n B. E. a. Whelan W. J. New aspects of glycogen metabolism, Advanc. Enzymol., v. 34, p. 285, 1971, bibliogr.; Whelan W. J. On the oridinof primer for glycogen synthesis, Trends Biochem. Sci., v. 1, p. 113, 1976, bibliogr.

B. H. Stepanenko; H. K. Permyakov (gist.).