From Big Medical Encyclopedia

GLYCOLYSIS (grech, glykys sweet + lysis destruction, disintegration) — the complex enzymatic process of transformation of glucose proceeding in tissues of animals and the person without oxygen consumption and leading to lactification and ATP.

With 6 H 12 O 6 + 2ADF + 2F neorg. —> 2CH 3 CHOHCOOH + 2ATF + 2H 2 O.

Exactly thanks to G. a human body and animals a row fiziol, functions in the conditions of insufficiency of oxygen can carry out.

When G. proceeds on air or in the atmosphere of oxygen, speak about aerobic G. V anaerobic conditions of G. — the only process in an animal organism delivering energy. In aerobic conditions of G. is the first stage of oxidizing transformation of glucose and other carbohydrates to end products of this process — carbonic acid and water. Processes, similar G., at plants and microorganisms different types are fermentations (see). For the first time the term «glycolysis» was offered by Lepine in 1890.

Reaction sequence in the course of G., also as well as their intermediate products, are well studied. G.'s reactions are catalyzed by eleven enzymes, the majority of which is marked out in the homogeneous, crystal or highly cleared look and which properties are carefully studied.

G. in skeletal muscles, in a liver, heart, a brain and other bodies is most intensive. In G.'s cell proceeds in a hyaloplasma.

The first enzymatic reaction (see the scheme) opening a reaction chain of G. is the reaction of interaction of D-glucose with ATP (2) leading to formation of glyukozo-6-phosphate and providing a possibility of further transformation of glucose in the course of. Reaction is catalyzed hexokinase (see). This reaction is followed by allocation of a significant amount of energy and therefore it is almost irreversible. In skeletal muscles and a liver glyukozo-6-phosphate in large numbers is formed also at a catabolism of a glycogen, i.e. at a glycogenolysis.

The second reaction of G. (the scheme, reaction 2) is the isomerization of glyukozo-6-phosphate in fruktozo-6-phosphate catalyzed glyukozofosfatizomerazy, not needing presence of any cofactors. The forming mix of two hexosemonophosphates consisting approximately for 80% from a glyukozo-6-fos-veil and for 20% of fruktozo-6-phosphate with impurity of nek-ry quantity of other phosphomonoesters carries the name of ether of Embden. The same mix, but consisting of glyukozo-6-phosphate almost half is called Robison's ether.

Fruktozo-6-fosfat, further in fosfofruktokinazny reaction (the scheme, reaction 3) at the expense of ATP is phosphorylated in fruktozo-1,6-diphosphate. Fructose diphosphate is specific substrate for G. whereas the previous reactions are characteristic not only of G., but also of an oxidative breakdown of carbohydrates. Fosfofruktokinaza — the regulatory enzyme having on a molecule 7, and according to some authors, 12 centers of binding of substrates, cofactors and inhibitors. Enzyme is activated by ions of bivalent metals, inorganic phosphate, ADF, AMF, cyclic 3', 5' - AMF. Activity of enzyme also increases in the presence of fruktozo-6-phosphate and fruktozo-1,6-diphosphate. Inhibit ATP enzyme and citrate.

The reaction catalyzed by fosfofruktokinazy is the most slowly current reaction of G. determining the speed of all process. The main factors in a cell controlling a fosfofruktokinaza are relative concentration of ATP and ADF. When size of the relation of ATF/ADF + F neorg. it is considerable that is reached in the course of oxidizing phosphorylations (see), there is an oppression of a fosfofruktokinaza, and G. is slowed down. At decrease in size of the relation of ATF/ADF + F neorg. G.'s intensity increases. In an idle muscle activity of a fosfofruktokinaza is low that is explained by high concentration of ATP (see. Adenosine triphosphoric acid ). In the course of work when there is an intensive consumption of ATP, activity of a fosfofruktokinaza increases that leads to G.'s intensification and consequently, and to the strengthened formation of ATP. At the diabetes, starvation and other conditions causing switching of energy balance to use of fats, the content of citrate can increase in a cell several times. The size of braking of a fosfofruktokinaza citrate reaches at the same time 70 — 80%.

The following stage G. catalyzes a fruktozodifosfataldolaz (the scheme, reaction 4). Fruktozo-1,6-difosfat is split on two phosphotrioses: dioksiatsetonfosfat and glitseraldegid-3-phosphate. Under the influence of a triozofosfatizomeraza (the scheme, reaction 5) there is an interconversion, phosphotrioses. Balance of this reaction is shifted towards formation of a dioksiatsetonfosfat: only 4% of glitseraldegid-3-phosphate are the share of 96% of a dioksiatsetonfosfat, but he also participates in further turning into process of. Thanks to high activity of a triozofosfatizomeraza preferential formation of a dioksiatsetonfosfat does not limit G.'s speed in general. The first stage of comes to an end with formation of glitseraldegid-3-phosphate (3-phosphoglyceric aldehyde).

Second stage of. is the general way of transformation of all carbohydrates and is considered as the most difficult and important part of process leading to formation of ATP. The central reaction of G. is reaction of the glycoclastic oxidoreduction interfaced to phosphorylation — the oxidation reaction of 3-phosphoglyceric aldehyde (the scheme, reaction 6) catalyzed glitseraldegidfosfatdegidrogenazy. This enzyme consists of four identical subunits, each of which represents a polypeptide chain with 330 amino-acid remains. Each subunit bears one molecule NAD+ and 4 free SH groups. During the reaction going in the presence of inorganic phosphate, NAD+ acts as hydrogen acceptor, chipping off from glitseraldegid-3-phosphate. At recovery of NAD+ there is a binding a glitseraldegid-3-fos-veil to a molecule of enzyme at the expense of SH-group of the last. The formed communication, high-energy, is fragile and is split under the influence of inorganic phosphate, at the same time is formed 1,3-disfosfoglitserinovy to - that (1,3 diphosphoglycerate). The subsequent reaction (the scheme, reaction 7) leads to transfer of the high-energy phosphatic rest on molecule ADF with formation of ATP and 3-phosphoglyceric to - you (3 phosphoglycerates). Ions of bivalent metals are necessary for the reaction catalyzed by phosphoglycerate kinase: Mg 2+ , Mn 2+ or Ca 2+ . Further (the scheme, reaction 8) 3-phosphoglyceric to - that turns in 2-phosphoglyceric to - that (2 phosphoglycerate). Reaction is catalyzed by phosphoglycerate-phosphomutase in the presence of two cofactors: ion of Mg 2+ and 2,3-diphosphoglyceric to - you. The following stage G. — formation of a fosfoyenolpiruvat, the high-energy predecessor of ATP (the scheme, reaction 9). Transformation 2-phosphoglyceric to - you (2 phosphoglycerates) in fosfoyenolpiruvat is carried out as a result of reaction of dehydration catalyzed phosphopyruvate-hydratase. The enzyme catalyzing this reaction needs Mg 2+ , Mn 2+ , Zn 2+ or Cd 2+ , which antagonists are ions of Ca 2+ or Sr 2+ . Reaction between fosfoyenolpiruvaty and ADF (the scheme, reaction 10) with education pyroracemic to - you (pyruvate) and ATP catalyze the pyruvatekinase demanding for manifestation of the ion activity of Mg 2+ or Mn 2+ and K +  ; Ca 2+ acts as the competitive antagonist of these ions. For the maximum activity the pyruvatekinase needs also presence of monovalent cations of K + , Rb + or Cs + , which antagonists are cations of Na + and Li + . Reversible recovery of pyruvate in milk to - that (lactate) at the expense of recovered OVER + (NADN) is a final stage G. (the scheme, reaction 11). Catalyzes reaction lactate dehydrogenase (see).

Thanks to three irreversible reactions — hexokinase, fosfofruktokinazny and piruvatkinazny G. in itself is irreversible process (its balance is shifted towards education milk to - you). Two molecules ATP are spent for the I stages of G., at the II stage four molecules ATP are formed. Thus, power efficiency of G. (only two molecules ATP on one molecule of glucose) is rather low. Nevertheless G.'s role is big since only thanks to it the organism can carry out a row fiziol, functions in the conditions of poor supply of fabrics and bodies oxygen. Such conditions are created, e.g., in vigorously working skeletal muscle. Presence of oxygen brakes G. (the phenomenon called by Pasteur's effect — see. Pasteur effect ). In a cardiac muscle in processes of formation of energy the glycoclastic way of disintegration of carbohydrates takes the small place. Activity of enzymes G. in heart is much lower, than in skeletal muscles. Actual speed of G. changes depending on supply of a cardiac muscle with oxygen and intensity in it oxidizing processes. But even at the most optimal conditions of supply with oxygen in a muscle of heart always goes. Substrates of glycoclastic reactions (fosforilirovanny sugar, pyruvate, milk to - that) are used by a cardiac muscle in processes of plastic metabolism of substances and in a cycle Tricarboxylic to - t (see. Tricarboxylic acids cycle ) as substrates of oxidation. Gets a big role of G. in heart in the conditions of deficit of oxygen. Rough aerobic G. occurs in tumors where it is the main source of energy. Tumoral fabrics are characterized by lack of effect of Pasteur. In them the regulating role of a fosfofruktokinaza is lost.

The normal current of G. is possible only if at fabric there are ADF, substrates for fosfoglitseratkinazny and piruvatkinazny reactions, and also OVER and inorganic phosphate, necessary for reaction of glycoclastic oxidoreduction (the oppression of glycoclastic oxidoreduction in a cardiac muscle caused by reduction of contents OVER was observed in the conditions of experimental myocarditis). The main, the reaction limiting G.'s speed is the reaction catalyzed fosfofruktokinazy (see the scheme, reaction 3). The second stage limiting speed and regulating G. after fosfofruktokinazny reaction is hexokinase reaction (see the scheme, reaction 1). The wide isofermental range of this enzyme causes a possibility of thin regulation of G. at its initial, starting stage. The dynamic nature of communication of a hexokinase with mitochondrions and microsomes, and also changes of properties of this enzyme at interaction with subcellular structures do the mechanism of regulation of G. very sensitive.

Lack of the regulating role of a fosfofruktokinaza and extremely high activity of a hexokinase turn a malignant tumor into the powerful pump which is continuously removing glucose from an organism. At the same time G.'s intensity such is that the difference between concentration of glucose in an arterial blood and fabric of a tumor reaches 60 — 80 mg of % (arterial blood) against zero (tumoral fabric).

Normal G.'s control is exercised also by a lactate dehydrogenase (LDG) and its isoenzymes (see the Lactate dehydrogenase) which are characterized by specific localization in bodies and fabrics. In fabrics with aerobic metabolism (tissues of heart, kidneys, erythrocytes) LDG-1 and LDG-2 prevail. These isoenzymes are inhibited even by small concentration of pyruvate that interferes with education milk to - you and promotes fuller oxidation of pyruvate in a cycle Tricarboxylic to - t. In tissues of the person, substantially dependent on the energy which is formed in the course of G. (skeletal muscles), the main isoenzymes of LDG are LDG-4 and LDG-5. Activity of LDG-5 is maximum at those concentration of pyruvate which inhibit LDG-1. Dominance of isoenzymes of LDG-4 and LDG-5 causes intensive anaerobic G. with bystry transformation of pyruvate in milk to - that. Noticeable increase in abundance of LDG-5 was noted at adaptation of organisms and cells in cultures to a hypoxia. In many tissues of the person (tissue of a spleen, pancreatic and thyroid glands, adrenal glands, limf, nodes) the isoenzyme of LDG-3 prevails. At fabrics of an embryo and fruit of the person there are all 5 isoenzymes of a lactate dehydrogenase among which LDG-3 prevails. Soon after the birth at the child the picture of distribution of isoenzymes in bodies and fabrics becomes same, as well as at the adult. Change of an isofermental range in an embryogenesis is especially expressed in skeletal muscles. At various myopathies (see) abnormal distribution of isoenzymes of LDG is observed: increase in one and reduction or even total disappearance of others. At the progressing muscular dystrophy (Dyushenn's disease) isoenzymes of LDG-1, LDG-2 and LDG-3 prevail. At other forms of muscular dystrophy (miotonichesky dystrophy, a dermatomyositis, a disease of Verdniga — Goffmanna) reduction or even lack of LDG-5 in skeletal muscles is characteristic that correlates with reduced education milk to - you at patients with these forms of myopathies after physical. works. At a row patol, states thanks to increase in permeability of cellular membranes isoenzymes of a lactate dehydrogenase in excess quantity come to blood. Activity of a lactate dehydrogenase and the nature of distribution of its isoenzymes in blood serum specifically change at myocardial infarction (see), diseases of a liver and biliary tract, rheumatism (see). The clinic applies the simple methods of definition of relative distribution of isoenzymes of a lactate dehydrogenase in blood serum based on their various electrophoretic mobility to differential diagnosis of these diseases.

In a human body and animals there are enzymatic mechanisms providing G.'s course in the opposite direction i.e. synthesis of glucose, and also a glycogen from milk to - you. This process carries the name of a gluconeogenesis; it intensively proceeds in a liver where in large numbers by a blood flow it is delivered milk to - that. Energy for implementation of this process is formed also in a liver as a result of full oxidation a nek-swarm of a part (apprx. 15%) milk to - you. Pyruvate or any connection turning in the course of a catabolism into pyruvate or one of intermediate products of a cycle Tricarboxylic to - t, and also so-called glycogenous amino acids can be predecessors of glucose in a gluconeogenesis.

The majority of stages of a gluconeogenesis represents the address of reactions of. Three reactions of G. — hexokinase, fosfofruktokinazny and piruvatkinazny — are irreversible therefore the gluconeogenesis makes a detour of these reactions.

The first reaction of a gluconeogenesis — transformation milk to - you in pyroracemic — catalyze a lactate dehydrogenase. Synthesis of a fosfoyenolpiruvat from pyruvate is carried out in several stages. The first stage is localized in mitochondrions.

Pyruvate under influence pyruvatecarboxymanholes (KF, active only in the presence of an atsetilkoferment And, is carboxylated with the assistance of CO 2 with formation of oxaloacetate. ATP therefore reaction products along with oxaloacetate are ADF and ortho-phosphate participates in reaction:

Oxaloacetate as a result decarboxylation and phosphorylations under influence phosphopyruvatecarboxymanholes (KF turns in fosfoyenol pyruvate. Serves as the donor of the phosphatic rest in reaction guanozintrifosfat or inozintrifosfat:

Fosfopiruvatkarboksilaza is present both at a hyaloplasma, and at mitochondrions, but distribution of enzyme at the person and animals variously. At Guinea pigs, rabbits, sheep, cows and at the person of a fosfopiruvatkarooksilaz is present at both fractions. In the embryonal liver of rats and Guinea pigs not capable to a gluconeogenesis, there is only a mitochondrial enzyme. In a hyaloplasma activity phosphopyruvatecarboxymanholes appears only during the post-natal period; at the same time the liver becomes capable to a gluconeogenesis.

As participates in a gluconeogenesis a phosphopyruvatecarboxymanhole transformation of oxaloacetate in fosfoyenolpiruvat happens in a hyaloplasma. The oxaloacetate formed in mitochondrions cannot pass into a hyaloplasma since the membrane of mitochondrions for it is impenetrable. In mitochondrions oxaloacetate is recovered in apple to - that (malate), is capable to diffuse edges from mitochondrions in a hyaloplasma where is oxidized with formation of oxaloacetate which, in turn, turns in fosfoyenol pyruvate.

The subsequent reactions of a gluconeogenesis catalyzed by enzymes G. lead to education fruktozo-1, 6 diphosphates. Transformation fruktozo-1, 6 diphosphates in fruktozo-6-phosphate, and then and glyukozo-6-phosphate in glucose catalyze the specific phosphatases which hydrolytic are chipping off inorganic phosphate.

At a gluconeogenesis fruktozo-1,6-diphosphatase (a geksozodifosfataza; KF catalyzes key reaction of D - fruktozo-1,6-diphosphate + H 2 O —> D - fruktozo-@-phosphate + ortho-phosphate) and respectively action, a cut renders on it ATP and AMF, is opposite to their action on a fosfofruktokinaza (see above): the geksozodifosfataza is activated under the influence of ATP and AMF is inhibited. When the size of the relation of ATF/ADF is low, in a cell there is a splitting of glucose when this size is high — splitting of glucose stops. In aerobic conditions is much more effective, than in anaerobic, from a cell inorganic phosphate y ADF is removed and ATP collects that leads to G.'s suppression and stimulation of a gluconeogenesis. Piruvatkarboksilaza is also sensitive to the size of the relation of ATF/ADF since ADF is inhibited. Atsetil-KOA activates to a pyruvatecarboxymanhole.

In G.'s regulation and a gluconeogenesis plays a large role insulin (see). At its insufficiency there is strengthening of glucose in blood (hyperglycemia), excess removal of glucose to urine (glucosuria) and reduction of maintenance of a glycogen in a liver. At the same time muscles lose ability to use glucose of blood in the course of G. In a liver at the general decrease in intensity of biosynthetic processes (biosynthesis of proteins, biosynthesis fat to - the t from glucose) observes the strengthened synthesis of enzymes of a gluconeogenesis. At administration of insulin sick diabetes all listed metabolic disturbances disappear: permeability for glucose of membranes of muscle cells is normalized, the ratio between G. and a gluconeogenesis is recovered. Insulin controls these processes at the genetic level as the regulator of synthesis of enzymes. It is the inductor of formation of key enzymes G.: hexokinase, fosfofruktokinaza and pyruvatekinase. At the same time insulin works as a repressor of synthesis of enzymes of a gluconeogenesis.

The wedge, signs of dominance of G. over an aerobic phase of disintegration of carbohydrates are observed most often at the hypoxemic states caused by various disturbances of blood circulation or breath, a hypobaropathy, anemia, decrease of the activity of system of fabric oxidizing enzymes at some infections and intoxications hypo - and avitaminosis, as a result of a relative hypoxia during the excessive muscular work. At G.'s strengthening there is an accumulation of pyruvate and a lactate to the corresponding acidulation of fabrics, change of acid-base equilibrium, reduction of alkaline reserves. At patients with a diabetes mellitus activation of processes of G. and insufficient resynthesis of a lactate in a glycogen of a liver also quite often lead to increase in content in blood of a lactate and pyruvate; in these cases acidosis can reach high degree with development of a diabetic lactic coma. Braking of resynthesis of a glycogen from the lactate and pyruvate formed as a result of G. is observed at defeats of a parenchyma of a liver (late stages of hepatitis, cirrhosis, etc.) therefore increase in content in blood serum of a lactate and pyruvate can serve as an indicator of an abnormal liver function.

High intensity of G. in tumoral fabrics is used for definition of sensitivity of tumors to a nek-eye to antineoplastic drugs: G.'s suppression in cuts of a tumor under the influence of the studied himiopreparat testifies to sensitivity to it this tumor.

Bibliography: Degli S. and Nikolson D. E. Metabolic ways, the lane with English, M., 1973, bibliogr.; L of e of N and N d-zher A. Biokhimiya, the lane with English, M., 1976; Problems of medical chemistry, under the editorship of V. S. Shapot and E. G. Larsky, M., 1973, bibliogr.; Uilkinsondzh. Isoenzymes, the lane with English, M., 1968.

G. A. Solovyova, G. K. Alekseev.