Glycolysis. Anoxic oxidation of glucose includes two stages Aerobic glycolysis of ATP

The subsequent stages of digestion of undigested or partially digested starch, as well as other carbohydrates in food, occur in small intestine in its different parts under the influence of hadrolytic enzymes - glycosidases.

Pancreatic α-amylase

In the duodenum, the pH of the gastric contents is neutralized, since the secretion of the pancreas has a pH of 7.5-8.0 and contains bicarbonates (HCO 3 -). With the secretion of the pancreas it enters the intestine pancreatic α -amylase. This enzyme hydrolyzes α-1,4-glycosidic bonds in starch and dextrins.

The products of starch digestion at this stage are the disaccharide maltose, containing 2 glucose residues linked by an α-1,4 bond. Isomaltose disaccharide is formed from those glucose residues that are located at branching points in the starch molecule and are connected by an α-1,6-glycosidic bond. In addition, oligosaccharides are formed containing 3-8 glucose residues linked by α-1,4- and α-1,6-links.

Pancreatic α-amylase, like salivary α-amylase, acts as an endoglycosidase. Pancreatic α-amylase does not cleave α-1,6-glycosidic bonds in starch. This enzyme also does not hydrolyze (3-1,4-glycosidic bonds that connect glucose residues in the cellulose molecule. Cellulose, therefore, passes through the intestines unchanged. However, undigested cellulose performs an important function as a ballast substance, giving food additional volume and positive influencing the digestion process. In addition, in the large intestine, cellulose can be exposed to bacterial enzymes and partially broken down to form alcohols, organic acids and CO 2. The products of bacterial breakdown of cellulose are important as stimulants of intestinal motility.

Maltose, isomaltose and triosesaccharides, formed in the upper intestine from starch, are intermediate products. Their further digestion occurs under the action of specific enzymes in the small intestine. The dietary disaccharides sucrose and lactose are also hydrolyzed by specific disaccharidases in the small intestine.

A peculiarity of the digestion of carbohydrates in the small intestine is that the activity of specific oligo- and disaccharidases in the intestinal lumen is low. But enzymes actively act on the surface of intestinal epithelial cells.

The inside of the small intestine has the shape of finger-shaped projections - villi, covered with epithelial cells. Epithelial cells, in turn, are covered with microvilli facing the intestinal lumen. These cells, together with the villi, form a brush border, due to which the contact surface of hydrolytic enzymes and their substrates in the intestinal contents increases. 1 mm 2 surfaces small intestine a person has 80-140 million villi.

Enzymes that cleave glycosidic bonds in disaccharides (disaccharidases) form enzymatic complexes localized on the outer surface of the cytoplasmic membrane of enterocytes.

Sucrase-isomaltase complex

This enzymatic complex consists of two polypeptide chains and has a domain structure. The sucrose-isomaltase complex is attached to the intestinal microvilli membrane using a hydrophobic (transmembrane) domain formed by the N-terminal part of the polypeptide. The catalytic center protrudes into the intestinal lumen.

Sucrase-isomaltase complex. 1 - sucrase; 2 - isomaltase;

3 - binding domain; 4 - transmembrane domain; 5 - cytoplasmic domain.

The association of this digestive enzyme with the membrane facilitates the efficient absorption of hydrolysis products into the cell.

The sucrose-isomaltase complex hydrolyzes sucrose and isomaltose, cleaving α-1,2- and α-1,6-glycosidic bonds. In addition, both enzyme domains have maltase and maltotriase activities, hydrolyzing α-1,4-glycosidic bonds in maltose and maltotriose (a trisaccharide formed from starch). The sucrase-isomaltase complex accounts for 80% of the total maltase activity in the intestine. But despite its inherent high maltase activity, this enzymatic complex is named according to its basic specificity. In addition, the sucrase subunit is the only enzyme in the intestine that hydrolyzes sucrose. The isomaltase subunit hydrolyzes glycosidic bonds in isomaltose at a higher rate than in maltose and maltotriose.

Effect of sucrase-isomaltase complex on maltose and maltotriose.

The effect of the sucrase-isomaltase complex on isomaltose and oligosaccharide.

In the jejunum, the content of the sucrase-isomaltase enzyme complex is quite high, but it decreases in the proximal and distal parts of the intestine.

Glycoamylase complex

This enzymatic complex catalyzes the hydrolysis of the α-1,4 bond between glucose residues in oligosaccharides, acting from the reducing end. According to the mechanism of action, this enzyme is classified as an exoglycosidase. The complex also cleaves bonds in maltose, acting like maltase. The glycoamylase complex contains two different catalytic subunits with slight differences in substrate specificity. The glycoamylase activity of the complex is greatest in the lower parts of the small intestine.

β-Glycosidase complex (lactase)

Lactase cleaves the β-1,4-glycosidic bonds between galactose and glucose in lactose.

This enzymatic complex is chemically a glycoprotein. Lactose, like other glycosidase complexes, is associated with the brush border and is distributed unevenly throughout the small intestine. Lactase activity fluctuates depending on age. Thus, lactase activity in the fetus is especially increased in late pregnancy and remains at a high level until 5-7 years of age. Then the enzyme activity decreases, amounting in adults to 10% of the activity level characteristic of children.

Trehalase- also a glycosidase complex that hydrolyzes the bonds between monomers in trehalose, a disaccharide found in mushrooms. Trehalose consists of two glucose residues linked by a glycosidic bond between the first anomeric carbon atoms.

The combined action of all these enzymes completes the digestion of food oligo- and polysaccharides with the formation of monosaccharides, the main of which is glucose. In addition to glucose, fructose and galactose are also formed from food carbohydrates, and in smaller quantities - mannose, xylose, and arabinose.

MECHANISM OF TRANSMEMBRANE TRANSFER OF GLUCOSE AND OTHER MONOSACCHARIDES INTO CELLS

Monosaccharides formed as a result of digestion are absorbed by intestinal epithelial cells using special transport mechanisms through the membranes of these cells.

Absorption of monosaccharides in the intestine

Transport of monosaccharides into the cells of the intestinal mucosa can be carried out in different ways: through facilitated diffusion along a concentration gradient and active transport through the symport mechanism due to the concentration gradient of Na + ions. Na + enters the cell along a concentration gradient, and at the same time glucose is transported against the concentration gradient (secondary active transport). Consequently, the greater the Na + gradient, the greater the flow of glucose into enterocytes. If the Na+ concentration in the extracellular fluid decreases, glucose transport decreases. The concentration gradient of Na +, which is the driving force of active symport, is created by the work of Na +, K + -ATPase, which works like a pump, pumping Na + out of the cell in exchange for K +. Unlike glucose, fructose is transported by a system independent of the sodium gradient.

Transfer to the cells of the intestinal mucosa via the mechanism of secondary active transport is also characteristic of galactose.

At different glucose concentrations in the intestinal lumen, different transport mechanisms operate. Thanks to active transport, intestinal epithelial cells can absorb glucose at very low concentrations in the intestinal lumen. If the concentration of glucose in the intestinal lumen is high, then it can be transported into the cell by facilitated diffusion. Fructose can also be absorbed in the same way. It should be noted that the rate of absorption of glucose and galactose is much higher than that of other monosaccharides.

After absorption, monosaccharides (mainly glucose) leave the cells of the intestinal mucosa through the membrane through facilitated diffusion into the circulatory system.

Glycolysis (from the Greek glycus - sweet and lysis - dissolution, decay) is a complex enzymatic process of glucose conversion that occurs in human and animal tissues without oxygen consumption. The end product of glycolysis is lactic acid. The process of glycolysis also produces ATP. The overall equation of glycolysis can be depicted as follows:

In an aerobic conditions Glycolysis is the only process in the animal body that supplies energy. It is thanks to the process of glycolysis that the human and animal body can carry out a number of physiological functions in conditions of oxygen deficiency. In cases where glycolysis occurs in the presence of oxygen, we speak of aerobic glycolysis. ( Under aerobic conditions, glycolysis can be considered the first stage of the oxidation of glucose to the final products of this process - carbon dioxide and water.)

The term “glycolysis” was first used by Lepin in 1890 to designate the process of loss of glucose in blood taken from circulatory system, i.e. in vitro.

In a number of microorganisms, processes similar to glycolysis are various types of fermentation.

The sequence of glycolytic reactions, as well as their intermediate products, is well studied. The process of glycolysis is catalyzed by eleven enzymes, most of which are isolated in homogeneous, crystalline or highly purified form and whose properties have been sufficiently studied. Note that glycolysis occurs in the hyaloplasm of the cell. In table Figure 27 shows data on the rate of anaerobic glycolysis in various tissues of the rat.

The first enzymatic reaction of glycolysis is phosphorylation, i.e., the transfer of an orthophosphate residue to glucose at the expense of ATP. The reaction is catalyzed by the enzyme hexokinase:

The formation of glucose-6-phosphate in the hexokinase reaction is associated with the release of a significant amount of free energy of the system and can be considered a practically irreversible process.

The enzyme hexokinase is capable of catalyzing the phosphorylation of not only D-glucose, but also other hexoses, in particular D-fructose, D-mannose, etc.

The second reaction of glycolysis is the conversion of glucose-6-phosphate under the action of the enzyme hexose phosphate isomerase into fructose 6-phosphate:

This reaction proceeds easily in both directions and does not require the presence of any cofactors.

In the third reaction, the resulting fructose-6-phosphate is again phosphorylated by a second ATP molecule. The reaction is catalyzed by the enzyme phosphofructokinase:

This reaction, similar to hexokinase, is practically irreversible; it occurs in the presence of magnesium ions and is the slowest reaction of glycolysis. In fact, this reaction determines the rate of glycolysis as a whole.

Phosphofructokinase is an allosteric enzyme. It is inhibited by ATP and stimulated by ADP and AMP. ( Phosphofructokinase activity is also inhibited by citrate. It has been shown that in diabetes, fasting and some other conditions, when fats are intensively used as a source of energy, the citrate content in tissue cells can increase several times. Under these conditions, a sharp inhibition of phosphofructokinase activity by citrate occurs.). At significant values ​​of the ATP/ADP ratio (which is achieved in the process of oxidative phosphorylation), the activity of phosphofructokinase is inhibited and glycolysis slows down. On the contrary, when this coefficient decreases, the intensity of glycolysis increases. Thus, in non-working muscle, the activity of phosphofructokinase is low, and the concentration of ATP is relatively high. During muscle work, intensive consumption of ATP occurs and the activity of phosphofructokinase increases, which leads to an increase in the process of glycolysis.

The fourth reaction of glycolysis is catalyzed by the enzyme aldolase. Under the influence of this enzyme, fructose-1,6-bisphosphate is split into two phosphotrioses:

This reaction is reversible. Depending on the temperature, equilibrium is established at at different levels. In general, with increasing temperature, the reaction shifts towards greater formation of triose phosphates (dioxyacetone phosphate and glyceraldehyde-3-phosphate).

The fifth reaction is the isomerization reaction of triose phosphates. This reaction is catalyzed by the enzyme triosephosphate isomerase:

The equilibrium of this isomerase reaction is shifted towards dihydroxyacetone phosphate: 95% dihydroxyacetone phosphate and about 5% glyceraldehyde-3-phosphate. However, only one of the two triose phosphates formed, namely glyceraldehyde-3-phosphate, can be directly involved in subsequent glycolytic reactions. As a result, as the aldehyde form of phosphotriose is consumed, dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate.

The formation of glyceraldehyde-3-phosphate completes the first stage of glycolysis. The second stage is the most complex and important part of glycolysis. It includes a redox reaction (glycolytic oxidoreduction) coupled with substrate phosphorylation, during which ATP is formed.

In the sixth reaction, glyceraldehyde-3-phosphate in the presence of the enzyme glyceraldehyde phosphate dehydrogenase ( 3-phosphoglyceraldehyde dehydrogenase), coenzyme NAD and inorganic phosphate undergo a peculiar oxidation with the formation of 1,3-diphosphoglyceric acid and the reduced form of NAD (NADH 2). This reaction is blocked by iodine or bromoacetate and proceeds in several stages. In total, this reaction can be represented as follows:

1,3-Diphosphoglyceric acid is a high-energy compound. The mechanism of action of glyceraldehyde-phosphate dehydrogenase is as follows: in the presence of inorganic phosphate, NAD acts as an acceptor of hydrogen, which is cleaved from glyceraldehyde-3-phosphate. During the formation of NADH 2, glyceraldehyde 3-phosphate binds to the enzyme molecule due to the SH groups of the latter. The resulting bond is rich in energy, but it is fragile and breaks down under the influence of inorganic phosphate. This produces 1,3-diphosphoglyceric acid.

The seventh reaction, which is catalyzed by phosphoglycerate kinase, transfers an energy-rich phosphate moiety (the phosphate group at position 1) to ADP to form ATP and 3-phosphoglyceric acid (3-phosphoglycerate):

Thus, due to the action of two enzymes (glyceraldehyde phosphate dehydrogenase and phosphoglycerate kinase), the energy released during the oxidation of the aldehyde group of glyceraldehyde-3-phosphate to the carboxyl group is stored in the form of ATP energy.

In the eighth reaction, intramolecular transfer of the remaining phosphate group occurs and 3-phosphoglyceric acid is converted to 2-phosphoglyceric acid (2-phosphoglycerate).

The reaction is easily reversible and occurs in the presence of Mg 2+ ions. The cofactor of the enzyme is also 2,3-diphosphoglyceric acid, similar to how in the phosphoglucomutase reaction the role of the cofactor was performed by glucose-1,6-bisphosphate:

In the ninth reaction, 2-phosphoglyceric acid, as a result of the elimination of a water molecule, is converted into phosphoenolpyruvic acid (phosphoenolpyruvate). In this case, the phosphate bond at position 2 becomes highly energetic. The reaction is catalyzed by the enzyme enolase:

Enolase is activated by divalent cations Mg 2+ or Mn 2+ and inhibited by fluoride.

In the tenth reaction, the high-energy bond is broken and the phosphate residue is transferred from phosphoenolpyruvic acid to ADP. This reaction is catalyzed by the enzyme pyruvate kinase:

The action of pyruvate kinase requires Mg 2+ or Mn 2+, as well as monovalent alkali metal cations (K + or others). Inside the cell, the reaction is practically irreversible.

In the eleventh reaction, lactic acid is formed as a result of the reduction of pyruvic acid. The reaction occurs with the participation of the enzyme lactate dehydrogenase and the coenzyme NADH 2+:

In general, the sequence of reactions occurring during glycolysis can be presented as follows (Fig. 84).

The pyruvate reduction reaction completes the internal redox cycle of glycolysis. In this case, NAD here plays only the role of an intermediate hydrogen carrier from glyceraldehyde-3-phosphate (sixth reaction) to pyruvic acid (eleventh reaction). The reaction of glycolytic oxidoreduction is schematically depicted below, and the stages at which ATP is formed are also indicated (Fig. 85).

The biological significance of the glycolysis process primarily lies in the formation of energy-rich phosphorus compounds. The first stage of glycolysis consumes two ATP molecules (hexokinase and phosphofructokinase reactions). In the second stage, four ATP molecules are formed (phosphoglycerate kinase and pyruvate kinase reactions).

Thus, the energy efficiency of glycolysis is two molecules of ATP per molecule of glucose.

It is known that the change in free energy during the breakdown of glucose into two molecules of lactic acid is about 210 kJ/mol:

Of this amount of energy, about 126 kJ is dissipated as heat, and 84 kJ is stored in the form of energy-rich phosphate bonds of ATP. The terminal high-energy bond in the ATP molecule corresponds to approximately 33.6-42.0 kJ/mol. Thus, the efficiency of anaerobic glycolysis is about 0.4.

The magnitude of free energy changes has been precisely determined for individual glycolytic reactions in intact human erythrocytes. It has been established that eight reactions of glycolysis are close to equilibrium, and three reactions (hexokinase, phosphofructokinase, pyruvate kinase) are far from it, since they are accompanied by a significant decrease in free energy, i.e. they are practically irreversible.

As already noted, the main rate-limiting reaction in glycolysis is the reaction catalyzed by phosphofructokinase. The second stage, which limits the rate and regulates glycolysis, is the hexokinase reaction. In addition, glycolysis is also controlled by lactate dehydrogenase (LDH) and its isoenzymes. In tissues with aerobic metabolism (tissue of the heart, kidneys, etc.), the isoenzymes LDH 1 and LDH 2 predominate. These isoenzymes are inhibited by even small concentrations of pyruvate, which prevents the formation of lactic acid and promotes more complete oxidation of pyruvate (more precisely, acetyl-CoA) in the tricarboxylic acid cycle.

In human tissues that rely heavily on energy generated by glycolysis (e.g. skeletal muscles), the main isoenzymes are LDH 5 and LDH 4. The activity of LDH 5 is maximum at those concentrations of pyruvate that inhibit LDH 1. The predominance of isoenzymes LDH 4 and LDH 5 causes intense anaerobic glycolysis with the rapid conversion of pyruvate to lactic acid.

Inclusion of other carbohydrates in the process of glycolysis

Pasteur effect

The decrease in the rate of glucose consumption and the cessation of lactate accumulation in the presence of oxygen is called the Pasteur effect. This phenomenon was first observed by L. Pasteur during his well-known studies concerning the role of fermentation in wine production. It was later shown that the Pasteur effect is also observed in animal and plant tissues, where O 2 inhibits anaerobic glycolysis. The significance of the Pasteur effect, i.e. the transition in the presence of O 2 from anaerobic glycolysis or fermentation to respiration, is to switch the cell to a more economical way of obtaining energy. As a result, the rate of consumption of a substrate, such as glucose, in the presence of O 2 is reduced. The molecular mechanism of the Pasteur effect appears to be competition between the respiratory and glycolytic (fermentation) systems for adenosine diphosphate (ADP), which is used to form adenosine triphosphate (ATP). As we already know, under aerobic conditions, the removal of PhN and ADP, the generation of ATP, and the removal of reduced NAD (NADH 2) occur much more efficiently than under anaerobic conditions. In other words, a decrease in the amount of Pn and ADP in the presence of oxygen and a corresponding increase in the amount of ATP lead to the suppression of anaerobic glycolysis.

Glycogenolysis

The process of anaerobic breakdown of glycogen is called glycogenolysis. The involvement of D-glucose units of glycogen in the process of glycolysis occurs with the participation of three enzymes - glycogen phosphorylase (or phosphorylase “a”), amylo-1,6-glucosidase and phosphoglucomutase.

Glucose-6-phosphate formed during the phosphoglucomutase reaction can be included in the process of glycolysis. After the formation of glucose-6-phosphate, the further pathways of glycolysis and glycogenolysis are completely identical:

During the process of glycogenolysis, not two, but three ATP molecules accumulate in the form of high-energy compounds (ATP is not wasted on the formation of glucose-6-phosphate). At first glance, the energy efficiency of glycogenolysis can be considered somewhat higher compared to the glycolysis process. However, it must be borne in mind that in the process of glycogen synthesis in tissues, ATP is consumed, therefore, in energy terms, glycogenolysis and glycolysis are almost equivalent.

Glycolysis is an enzymatic process of anaerobic non-hydrolytic breakdown of carbohydrates (mainly glucose) in human and animal cells, accompanied by the synthesis of adenosine triphosphoric acid (ATP), the main accumulator of chemical energy in the cell, and ending with the formation of lactic acid (lactate). In plants and microorganisms, similar processes are various types fermentation (Fermentation). G. is the most important anaerobic pathway for the breakdown of carbohydrates (carbohydrates), playing a significant role in the metabolism and energy (Metabolism and energy). Under conditions of oxygen deficiency, the only process that supplies energy to carry out the physiological functions of the body is gas, and under aerobic conditions gas represents the first stage of the oxidative transformation of glucose (Glucose) and other carbohydrates to the final products of their breakdown - CO2 and H2O (see Respiration tissue). Intense G. occurs in skeletal muscles, where it provides the opportunity for the development of maximum activity of muscle contraction under anaerobic conditions, as well as in the liver, heart, and brain. G.'s reactions occur in the cytosol.

Glycolysis (phosphotriose pathway, or Embden-Meyerhof shunt, or Embden-Meyerhof-Parnas pathway) is an enzymatic process of sequential breakdown of glucose in cells, accompanied by the synthesis of ATP. Glycolysis under aerobic conditions leads to the formation of pyruvic acid (pyruvate), glycolysis under anaerobic conditions leads to the formation of lactic acid (lactate). Glycolysis is the main pathway of glucose catabolism in animals.

The glycolytic pathway consists of 10 sequential reactions, each of which is catalyzed by a separate enzyme.

The process of glycolysis can be divided into two stages. The first stage, which takes place with the energy consumption of 2 ATP molecules, consists of the splitting of a glucose molecule into 2 molecules of glyceraldehyde-3-phosphate. At the second stage, NAD-dependent oxidation of glyceraldehyde-3-phosphate occurs, accompanied by the synthesis of ATP. Glycolysis itself is a completely anaerobic process, that is, it does not require the presence of oxygen for reactions to occur.

Glycolysis is one of the oldest metabolic processes, known in almost all living organisms. Presumably, glycolysis appeared more than 3.5 billion years ago in primordial prokaryotes.

Localization

In the cells of eukaryotic organisms, ten enzymes that catalyze the breakdown of glucose to PVC are located in the cytosol, all other enzymes related to energy metabolism are in mitochondria and chloroplasts. Glucose enters the cell in two ways: sodium-dependent symport (mainly for enterocytes and renal tubular epithelium) and facilitated diffusion of glucose using carrier proteins. The work of these transporter proteins is controlled by hormones and, primarily, insulin. Insulin most strongly stimulates glucose transport in muscles and adipose tissue.

Result

The result of glycolysis is the conversion of one molecule of glucose into two molecules of pyruvic acid (PVA) and the formation of two reducing equivalents in the form of the coenzyme NAD∙H.

The complete equation for glycolysis is:

Glucose + 2NAD+ + 2ADP + 2Pn = 2NAD∙H + 2PVK + 2ATP + 2H2O + 2H+.

In the absence or deficiency of oxygen in the cell, pyruvic acid undergoes reduction to lactic acid, then the general equation of glycolysis will be as follows:

Glucose + 2ADP + 2Pn = 2lactate + 2ATP + 2H2O.

Thus, during the anaerobic breakdown of one glucose molecule, the total net ATP output makes up two molecules obtained in reactions of substrate phosphorylation of ADP.

In aerobic organisms, the end products of glycolysis undergo further transformations in biochemical cycles related to cellular respiration. As a result, after complete oxidation of all metabolites of one glucose molecule, at the last stage of cellular respiration - oxidative phosphorylation, which occurs on the mitochondrial respiratory chain in the presence of oxygen - an additional 34 or 36 ATP molecules are synthesized for each glucose molecule.

Path

The first reaction of glycolysis is the phosphorylation of a glucose molecule, which occurs with the participation of the tissue-specific enzyme hexokinase with the energy consumption of 1 molecule of ATP; the active form of glucose is formed - glucose-6-phosphate (G-6-P):

For the reaction to occur, the presence of Mg2+ ions in the medium is necessary, with which the ATP molecule is complexly bound. This reaction is irreversible and is the first key reaction of glycolysis.

Phosphorylation of glucose has two purposes: firstly, due to the fact that the plasma membrane, permeable to the neutral glucose molecule, does not allow negatively charged G-6-P molecules to pass through, phosphorylated glucose is locked inside the cell. Secondly, during phosphorylation, glucose is converted into an active form that can participate in biochemical reactions and be included in metabolic cycles. Glucose phosphorylation is the only reaction in the body in which glucose itself is involved.

The hepatic isoenzyme of hexokinase, glucokinase, is important in regulating blood glucose levels.

In the following reaction (2), G-6-P is converted to fructose-6-phosphate (F-6-P) by the enzyme phosphoglucoisomerase:

No energy is required for this reaction and the reaction is completely reversible. At this stage, fructose can also be included in the glycolysis process through phosphorylation.

Then, almost immediately, two reactions follow one another: irreversible phosphorylation of fructose-6-phosphate (3) and reversible aldol cleavage of the resulting fructose-1,6-biphosphate (F-1,6-bP) into two trioses (4).

Phosphorylation of P-6-P is carried out by phosphofructokinase with the expenditure of energy of another ATP molecule; This is the second key reaction of glycolysis; its regulation determines the intensity of glycolysis as a whole.

Aldol cleavage of F-1,6-bP occurs under the action of fructose-1,6-biphosphate aldolase:

As a result of the fourth reaction, dihydroxyacetone phosphate and glyceraldehyde-3-phosphate are formed, and the first almost immediately, under the action of phosphotriose isomerase, transforms into the second (5), which is involved in further transformations:

Each glyceraldehyde phosphate molecule is oxidized by NAD+ in the presence of glyceraldehyde phosphate dehydrogenase to 1,3-diphosphoglycerate(6):

This is the first reaction of substrate phosphorylation. From this moment, the process of glucose breakdown ceases to be unprofitable in terms of energy, since the energy costs of the first stage are compensated: 2 ATP molecules are synthesized (one for each 1,3-diphosphoglycerate) instead of the two spent in reactions 1 and 3. For this reaction to occur the presence of ADP in the cytosol is required, that is, when there is an excess of ATP in the cell (and a lack of ADP), its speed decreases. Since ATP, which is not metabolized, is not deposited in the cell but is simply destroyed, this reaction is an important regulator of glycolysis.

Then sequentially: phosphoglycerol mutase forms 2-phosphoglycerate (8):

Enolase forms phosphoenolpyruvate (9):

And finally, the second reaction of substrate phosphorylation of ADP occurs with the formation of the enol form of pyruvate and ATP (10):

The reaction occurs under the action of pyruvate kinase. This is the last key reaction of glycolysis. Isomerization of the enol form of pyruvate to pyruvate occurs non-enzymatically.

From the moment of formation of F-1,6-bP, only reactions 7 and 10 occur with the release of energy, in which substrate phosphorylation of ADP occurs.

Further development

The final fate of pyruvate and NAD∙H produced during glycolysis depends on the organism and conditions within the cell, particularly the presence or absence of oxygen or other electron acceptors.

In anaerobic organisms, pyruvate and NAD∙H are further fermented. During lactic acid fermentation, for example in bacteria, pyruvate is reduced to lactic acid by the enzyme lactate dehydrogenase. In yeast, a similar process is alcoholic fermentation, where the end products are ethanol and carbon dioxide. Butyric acid and citric acid fermentation are also known.

Butyric acid fermentation:

glucose → butyric acid + 2 CO2 + 2 H2O.

Alcoholic fermentation:

glucose → 2 ethanol + 2 CO2.

Citric acid fermentation:

glucose → citric acid + 2 H2O.

Fermentation is important in the food industry.

In aerobes, pyruvate typically enters the tricarboxylic acid cycle (Krebs cycle), and NAD∙H is ultimately oxidized by oxygen in the respiratory chain in mitochondria during the process of oxidative phosphorylation.

Although human metabolism is predominantly aerobic, anaerobic oxidation occurs in intensively working skeletal muscles. Under conditions of limited access to oxygen, pyruvate is converted into lactic acid, as occurs during lactic acid fermentation in many microorganisms:

PVK + NAD∙H + H+ → lactate + NAD+.

Muscle pain that occurs some time after unusual intense physical activity, are associated with the accumulation of lactic acid in them.

The formation of lactic acid is a dead-end branch of metabolism, but is not the final product of metabolism. Under the action of lactate dehydrogenase, lactic acid is oxidized again, forming pyruvate, which is involved in further transformations.

To understand what glycolysis is, you will have to turn to Greek terminology, because this term comes from Greek words: glycos - sweet and lysis - splitting. The name glucose comes from the word Glykos. Thus, this term refers to the process of saturating glucose with oxygen, as a result of which one molecule of a sweet substance breaks down into two microparticles of pyruvic acid. Glycolysis is a biochemical reaction that occurs in living cells and is aimed at breaking down glucose. There are three options for the breakdown of glucose, and aerobic glycolysis is one of them.

This process consists of a number of intermediate chemical reactions accompanied by the release of energy. This is the main essence of glycolysis. The released energy is spent on the general vital activity of a living organism. The general formula for the breakdown of glucose looks like this:

Glucose + 2NAD + + 2ADP + 2Pi → 2 pyruvate + 2NADH + 2H + + 2ATP + 2H2O

Aerobic oxidation of glucose followed by the breakdown of its six-carbon molecule is carried out through 10 intermediate reactions. The first 5 reactions are united by the preparatory phase of preparation, and subsequent reactions are aimed at the formation of ATP. During the reactions, stereoscopic sugar isomers and their derivatives are formed. The main accumulation of energy by cells occurs in the second phase, associated with the formation of ATP.

Stages of oxidative glycolysis. Phase 1.

Aerobic glycolysis has two phases.

The first phase is preparatory. In it, glucose reacts with 2 ATP molecules. This phase consists of 5 successive steps of biochemical reactions.

1st stage. Phosphorylation of glucose

Phosphorylation, that is, the process of transfer of phosphoric acid residues in the first and subsequent reactions, is carried out by molecules of adesine triphosphoric acid.

In the first step, phosphoric acid residues from adesine triphosphate molecules are transferred to the molecular structure of glucose. The process produces glucose-6-phosphate. Hexokinase acts as a catalyst in the process, accelerating the process with the help of magnesium ions acting as a cofactor. Magnesium ions are also involved in other glycolytic reactions.

2nd stage. Formation of glucose-6-phosphate isomer

At the 2nd stage, isomerization of glucose-6-phosphate into fructose-6-phosphate occurs.

Isomerization is the formation of substances that have the same weight and composition of chemical elements, but have different properties due to the different arrangement of atoms in the molecule. Isomerization of substances is carried out under the influence of external conditions: pressure, temperatures, catalysts.

In this case, the process is carried out under the action of a phosphoglucose isomerase catalyst with the participation of Mg + ions.

3rd stage. Phosphorylation of fructose 6-phosphate

At this stage, the phosphoryl group is added due to ATP. The process is carried out with the participation of the enzyme phosphofructokinase-1. This enzyme is intended only to participate in hydrolysis. The reaction produces fructose 1,6-bisphosphate and the nucleotide adesine triphosphate.

ATP is adesine triphosphate, a unique source of energy in a living organism. It is a rather complex and bulky molecule consisting of hydrocarbon, hydroxyl groups, nitrogen and phosphoric acid groups with one free bond, assembled in several cyclic and linear structures. The release of energy occurs as a result of the interaction of phosphoric acid residues with water. ATP hydrolysis is accompanied by the formation of phosphoric acid and the release of 40-60 J of energy, which the body spends on its vital functions.

But first, phosphorylation of glucose must occur due to the adesine triphosphate molecule, that is, the transfer of a phosphoric acid residue into glucose.

4th stage. Fructose 1,6-bisphosphate breakdown

In the fourth reaction, fructose 1,6-bisphosphate breaks down into two new substances.

• Dihydroxyacetone phosphate,
• Glyceraldehyde-3-phosphate.

In this chemical process, the catalyst is aldolase, an enzyme involved in energy metabolism and necessary in diagnosing a number of diseases.

5th stage. Formation of triose phosphate isomers

And finally, the last process is the isomerization of triose phosphates.

Glyceral 3-phosphate will continue to participate in the process of aerobic hydrolysis. And the second component, dihydroxyacetone phosphate, is converted into glyceraldehyde-3-phosphate with the participation of the enzyme triosephosphate isomerase. But this transformation is reversible.

Phase 2. Synthesis of Adesine Triphosphate

In this phase of glycolysis, biochemical energy will be accumulated in the form of ATP. Adesine triphosphate is formed from adesine diphosphate by phosphorylation. NADH is also formed.

The abbreviation NADH has a very complex and difficult to remember decoding for a non-specialist - Nicotinamide adenine dinucleotide. NADH is a coenzyme, a non-protein compound involved in the chemical processes of a living cell. It exists in two forms:

1. oxidized (NAD + , NADox);
2. reduced (NADH, NADred).

In metabolism, NAD takes part in redox reactions by transporting electrons from one chemical process to another. By donating or accepting an electron, the molecule is converted from NAD + to NADH, and vice versa. In the living body, NAD is produced from the amino acids tryptophan or aspartate.

Two microparticles of glyceraldehyde-3-phosphate undergo reactions during which pyruvate and 4 ATP molecules are formed. But the final yield of adesine triphosphate will be 2 molecules, since two were spent in the preparatory phase. The process continues.

6th step – oxidation of glyceraldehyde-3-phosphate

In this reaction, oxidation and phosphorylation of glyceraldehyde-3-phosphate occurs. The result is 1,3-diphosphoglyceric acid. Glyceraldehyde-3-phosphate dehydrogenase is involved in accelerating the reaction

The reaction occurs with the participation of energy received from the outside, which is why it is called endergonic. Such reactions proceed in parallel with exergonic ones, that is, releasing and releasing energy. In this case, the following process serves as such a reaction.

7th stage. Transfer of a phosphate group from 1,3-diphosphoglycerate to adesine diphosphate

In this intermediate reaction, the phosphoryl group is transferred by phosphoglycerate kinase from 1,3-diphosphoglycerate to adesine diphosphate. The result is 3-phosphoglycerate and ATP.

The enzyme phosphoglycerate kinase gets its name from its ability to catalyze reactions in both directions. This enzyme also transports a phosphate residue from adesine triphosphate to 3-phosphoglycerate.

The 6th and 7th reactions are often considered as a single process. 1,3-diphosphoglycerate is considered as an intermediate product. Together, the 6th and 7th reactions look like this:

Glyceraldehyde-3-phosphate + ADP + Pi + NAD + ⇌ 3 -phosphoglycerate + ATP + NADH + H +, ΔG′о = −12.2 kJ/mol.

And in total these 2 processes release part of the energy.

8th stage. Transfer of phosphoryl group from 3-phosphoglycerate.

The production of 2-phosphoglycerate is a reversible process; it occurs under the catalytic action of the enzyme phosphoglycerate mutase. The phosphoryl group is transferred from the divalent carbon atom of 3-phosphoglycerate to the trivalent carbon atom of 2-phosphoglycerate, resulting in the formation of 2-phosphoglyceric acid. The reaction takes place with the participation of positively charged magnesium ions.

9th stage. Release of water from 2-phosphoglycerate

This reaction is essentially the second reaction of glucose breakdown (the first was the 6th step reaction). In it, the enzyme phosphopyruvate hydratase stimulates the abstraction of water from the C atom, that is, the process of elimination from the 2-phosphoglycerate molecule and the formation of phosphoenolpyruvate (phosphoenolpyruvic acid).

10th and final step. Transfer of phosphate residue from PEP to ADP

The final reaction of glycolysis involves coenzymes - potassium, magnesium and manganese, and the enzyme pyruvate kinase acts as a catalyst.

The conversion of the enol form of pyruvic acid to the keto form is a reversible process, and both isomers are present in cells. The process of transferring isometric substances from one to another is called tautomerization.

What is anaerobic glycolysis?

Along with aerobic glycolysis, that is, the breakdown of glucose with the participation of O2, there is also the so-called anaerobic breakdown of glucose, in which oxygen does not participate. It also consists of ten sequential reactions. But where does the anaerobic stage of glycolysis occur, is it associated with the processes of oxygen breakdown of glucose, or is it an independent biochemical process? Let’s try to figure it out.

Anaerobic glycolysis is the breakdown of glucose in the absence of oxygen to form lactate. But during the formation of lactic acid, NADH does not accumulate in the cell. This process is carried out in those tissues and cells that function under conditions oxygen starvation– hypoxia. These tissues primarily include skeletal muscles. In red blood cells, despite the presence of oxygen, lactate is also formed during glycolysis, because blood cells lack mitochondria.

Anaerobic hydrolysis occurs in the cytosol (liquid part of the cytoplasm) of cells and is the only act that produces and supplies ATP, since in this case oxidative phosphorylation does not work. Oxidative processes require oxygen, but anaerobic glycolysis does not have it.

Both pyruvic and lactic acids serve as sources of energy for the muscles to perform certain tasks. Excess acids enter the liver, where under the action of enzymes they are again converted into glycogen and glucose. And the process begins again. The lack of glucose is compensated for by nutrition - eating sugar, sweet fruits, and other sweets. So you can’t completely give up sweets for the sake of your figure. The body needs sucrose, but in moderation.

In this article we will take a detailed look at aerobic glycolysis, its processes, and analyze the stages and stages. Let's get acquainted with anaerobic, learn about the evolutionary modifications of this process and determine its biological significance.

What is glycolysis

Glycolysis is one of three forms of glucose oxidation, in which the oxidation process itself is accompanied by the release of energy, which is stored in NADH and ATP. In the process of glycolysis, a molecule is converted into two molecules of pyruvic acid.

Glycolysis is a process that occurs under the influence of various biological catalysts - enzymes. The main oxidizing agent is oxygen - O 2, however, the processes of glycolysis can occur in its absence. This type of glycolysis is called anaerobic glycolysis.

The process of glycolysis in the absence of oxygen

Anaerobic glycolysis is a stepwise process of glucose oxidation, in which glucose is not completely oxidized. One molecule of pyruvic acid is formed. And with energy point In view, glycolysis without the participation of oxygen (anaerobic) is less beneficial. However, when oxygen enters the cell, the anaerobic oxidation process can turn into aerobic and proceed in its full form.

Mechanisms of glycolysis

The process of glycolysis is the decomposition of six-carbon glucose into three-carbon pyruvate in the form of two molecules. The process itself is divided into 5 stages of preparation and 5 stages during which energy is stored in ATP.

The glycolysis process of 2 stages and 10 stages is as follows:

• Stage 1, stage 1 - phosphorylation of glucose. At the sixth carbon atom in glucose, the saccharide itself is activated through phosphorylation.
• Stage 2 - isomerization of glucose-6-phosphate. At this stage, phosphoglucose imerase catalytically converts glucose into fructose-6-phosphate.
• Stage 3 - Fructose-6-phosphate and its phosphorylation. This step involves the formation of fructose-1,6-bisphosphate (aldolase) by the action of phosphofructokinase-1, which accompanies the phosphoryl group from adenosine triphosphate to the fructose molecule.
• Step 4 is the process of cleavage of aldolase to form two triose phosphate molecules, namely eldose and ketose.
• Stage 5 - triose phosphates and their isomerization. At this stage, glyceraldehyde-3-phosphate is sent to subsequent stages of glucose breakdown, and dihydroxyacetone phosphate is converted to the form of glyceraldehyde-3-phosphate under the influence of an enzyme.
• Stage 2, stage 6 (1) - Glyceraldehyde-3-phosphate and its oxidation - a stage in which this molecule is oxidized and phosphorylated to diphosphoglycerate-1,3.
• Stage 7 (2) - is aimed at transferring the phosphate group to ADP from 1,3-diphosphoglycerate. The end products of this stage are the formation of 3-phosphoglycerate and ATP.
• Stage 8 (3) - transition from 3-phosphoglycerate to 2-phosphoglycerate. This process occurs under the influence of the enzyme phosphoglycerate mutase. A prerequisite for a chemical reaction to occur is the presence of magnesium (Mg).
• Step 9 (4) - 2 phosphoglycert is dehydrated.
• Stage 10 (5) - phosphates obtained as a result of the previous stages are transferred to ADP and PEP. Energy is transferred from phosphoenulpyrovate to ADP. For the reaction to occur, the presence of potassium (K) and magnesium (Mg) ions is necessary.

Modified forms of glycolysis

The process of glycolysis can be accompanied by additional production of 1,3 and 2,3-bisphosphoglycerates. 2,3-phosphoglycerate, under the influence of biological catalysts, is able to return to glycolysis and transform into the form of 3-phosphoglycerate. The role of these enzymes is varied, for example, 2,3-bisphosphoglycerate, being in hemoglobin, causes oxygen to pass into tissues, promoting dissociation and reducing the affinity of O 2 and red blood cells.

Many bacteria change the forms of glycolysis at various stages, reducing their total amount or modifying them under the influence of different enzymes. A small proportion of anaerobes have other methods of carbohydrate decomposition. Many thermophiles have only 2 glycolytic enzymes, enolase and pyruvate kinase.

Glycogen and starch, disaccharides and other types of monosaccharides

Aerobic glycolysis is a process that is also characteristic of other types of carbohydrates, and specifically it is inherent in starch, glycogen, and most disaccharides (manose, galactose, fructose, sucrose and others). The functions of all types of carbohydrates are generally aimed at obtaining energy, but may differ in the specifics of their purpose, use, etc. For example, glycogen is amenable to glycogenesis, which is essentially a phospholytic mechanism aimed at obtaining energy from the breakdown of glycogen. Glycogen itself can be stored in the body as a reserve source of energy. For example, glucose received during a meal, but not absorbed by the brain, accumulates in the liver and will be used when there is a lack of glucose in the body in order to protect the individual from serious disruptions of homeostasis.

The importance of glycolysis

Glycolysis is a unique, but not the only type of glucose oxidation in the body, the cell of both prokaryotes and eukaryotes. Glycolytic enzymes are water soluble. The glycolysis reaction in some tissues and cells can only occur in this way, for example, in the brain and liver nephron cells. Other methods of glucose oxidation are not used in these organs. However, the functions of glycolysis are not the same everywhere. For example, adipose tissue and liver, during the digestion process, extract the necessary substrates from glucose for the synthesis of fats. Many plants use glycolysis as a way to obtain the bulk of their energy.