Aerobic and anaerobic glycolysis. What is their role in the life of the human body? Summary equation of glycolysis Aerobic glycolysis ATP

IN anaerobic process pyruvic acid is reduced to lactic acid (lactate), therefore, in microbiology, anaerobic glycolysis is called lactic acid fermentation. Lactate is not further converted into anything, the only way to utilize lactate is to oxidize it back to pyruvate.

Many body cells are capable of anaerobic oxidation of glucose. For erythrocytes it is the only source of energy. Cells skeletal muscles due to the oxygen-free breakdown of glucose, they are able to perform powerful, fast, intense work, such as sprinting, stress in strength sports. Outside of physical exertion, oxygen-free oxidation of glucose in cells is enhanced during hypoxia - with various types of anemia, at circulatory disorders tissue, regardless of cause.

glycolysis

Anaerobic glucose conversion takes place in cytosol and includes two stages of 11 enzymatic reactions.

First step of glycolysis

The first step in glycolysis is preparatory, here ATP energy is consumed, glucose is activated and the formation of glucose from it triose phosphates.

First reaction glycolysis is reduced to the conversion of glucose into a reactive compound due to phosphorylation of the 6th carbon atom not included in the ring. This reaction is the first in any glucose conversion, catalyzed by hexokinase.

Second reaction necessary to remove one more carbon atom from the ring for its subsequent phosphorylation (enzyme glucose phosphate isomerase). As a result, fructose-6-phosphate is formed.

Third reaction– enzyme phosphofructokinase phosphorylates fructose-6-phosphate with the formation of an almost symmetrical fructose-1,6-diphosphate molecule. This reaction is central to the regulation of the rate of glycolysis.

IN fourth reaction fructose 1,6-diphosphate cut in half fructose-1,6-diphosphate- aldolase with the formation of two phosphorylated triose isomers - aldoses glyceraldehyde(GAF) and ketoses dihydroxyacetone(DAF).

Fifth reaction preparatory stage - the transition of glyceraldehyde phosphate and dihydroxyacetone phosphate into each other with the participation triose phosphate isomerase. The equilibrium of the reaction is shifted in favor of dihydroxyacetone phosphate, its share is 97%, the share of glyceraldehyde phosphate is 3%. This reaction, for all its simplicity, determines the fate of glucose:

• with a lack of energy in the cell and activation of glucose oxidation, dihydroxyacetone phosphate turns into glyceraldehyde phosphate, which is further oxidized at the second stage of glycolysis,
• with a sufficient amount of ATP, on the contrary, glyceraldehyde phosphate isomerizes into dihydroxyacetone phosphate, and the latter is sent to the synthesis of fats.

Second stage of glycolysis

The second stage of glycolysis is energy release contained in glyceraldehyde phosphate and storing it in the form ATP.

sixth reaction glycolysis (enzyme glyceraldehyde phosphate dehydrogenase) - the oxidation of glyceraldehyde phosphate and the addition of phosphoric acid to it leads to the formation of a high-energy compound of 1,3-diphosphoglyceric acid and NADH.

IN seventh reaction(enzyme phosphoglycerate kinase) the energy of the phosphoester bond contained in 1,3-diphosphoglycerate is spent on the formation of ATP. The reaction received an additional name - , which specifies the energy source for obtaining macroergic bonds in ATP (from the reaction substrate) in contrast to oxidative phosphorylation (the use of the energy of the electrochemical gradient of hydrogen ions on the mitochondrial membrane).

Eighth reaction- 3-phosphoglycerate synthesized in the previous reaction under the influence of phosphoglycerate mutase isomerizes to 2-phosphoglycerate.

Ninth reaction– enzyme enolase detaches a water molecule from 2-phosphoglyceric acid and leads to the formation of a macroergic phosphoester bond in the composition of phosphoenolpyruvate.

Tenth reaction glycolysis is another substrate phosphorylation reaction- consists in the transfer of high-energy phosphate from phosphoenolpyruvate to ADP by pyruvate kinase and the formation of pyruvic acid.

The last reaction of oxygen-free oxidation of glucose, eleventh- formation of lactic acid from pyruvate under the action of lactate dehydrogenase. It is important that this reaction occurs only in anaerobic conditions. This reaction is necessary for the cell, since NADH, which is formed in the 6th reaction, cannot be oxidized in mitochondria in the absence of oxygen.

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

Pancreatic α-amylase

In the duodenum, the pH of the gastric contents is neutralized, since the secret of the pancreas has a pH of 7.5-8.0 and contains bicarbonates (HCO 3 -). With the secret of the pancreas 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 maltose disaccharide containing 2 glucose residues linked by an α-1,4 bond. Of those glucose residues that are in the starch molecule at the branching sites and are connected by an α-1,6-glycosidic bond, isomaltose disaccharide is formed. In addition, oligosaccharides containing 3-8 glucose residues linked by α-1,4 and α-1,6 bonds are formed.

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 intestine unchanged. Nevertheless, undigested cellulose performs the important function of a ballast substance, giving food additional volume and positively In addition, in the large intestine, cellulose can be exposed to the action of 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 triose sugars, formed in the upper intestines from starch, are intermediate products. Their further digestion occurs under the action of specific enzymes in the small intestine. Dietary disaccharides sucrose and lactose are also hydrolyzed by specific disaccharidases in the small intestine.

The peculiarity of carbohydrate digestion in the small intestine is that the activity of specific oligo- and disaccharidases in the intestinal lumen is low. But enzymes are active on the surface of intestinal epithelial cells.

The small intestine from the inside has the form of finger-shaped outgrowths - 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. For 1 mm 2 of the surface of the small intestine in humans, there are 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 sucrase-isomaltase complex is attached to the membrane of the intestinal microvilli with the help of a hydrophobic (transmembrane) domain formed by the N-terminal part of the polypeptide. The catalytic site protrudes into the intestinal lumen.

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

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

The connection of this digestive enzyme with the membrane contributes to the efficient absorption of hydrolysis products by the cell.

Sucrase-isomaltase complex hydrolyzes sucrose and isomaltose, splitting 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 derived from starch). The sucrase-isomaltase complex accounts for 80% of all intestinal maltase activity. But despite its inherent high maltase activity, this enzymatic complex is named in accordance with the main specificity. In addition, the sucrose subunit is the only enzyme in the intestine that hydrolyzes sucrose. The isomaltase subunit hydrolyzes glycosidic bonds in isomaltose at a faster rate than in maltose and maltotriose.

The action of the sucrase-isomaltase complex on maltose and maltotriose.

The action 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 referred to as exoglycosidases. The complex also cleaves bonds in maltose, acting like maltase. The glycoamylase complex contains two different catalytic subunits, resulting in slight differences in substrate specificity. 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 unevenly distributed throughout the small intestine. Lactase activity fluctuates with age. Thus, the activity of lactase in the fetus is especially increased in late pregnancy and remains at a high level until the age of 5-7 years. Then the activity of the enzyme decreases, amounting in adults to 10% of the level of activity characteristic of children.

Tregalase- also a glycosidase complex that hydrolyzes 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, in a smaller amount - 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

The transport of monosaccharides into the cells of the intestinal mucosa can be carried out in different ways: by facilitated diffusion along the concentration gradient and active transport by the symport mechanism due to the concentration gradient of Na + ions. Na + enters the cell along the concentration gradient, and at the same time glucose is transported against the concentration gradient (secondary active transport). Therefore, the greater the Na + gradient, the greater the entry of glucose into enterocytes. If the concentration of Na + 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 by the mechanism of secondary active transport is also characteristic of galactose.

At different concentrations of glucose in the intestinal lumen, various mechanisms of transport "work". Due 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 by facilitated diffusion into the circulatory system.

Glucose catabolism 1 is accompanied by the consumption of 2 ATP molecules for substrate phosphorylation of hexoses, the formation of 4 ATP molecules in substrate phosphorylation reactions, the reduction of 2 NADH 2 molecules and the synthesis of 2 PVC molecules. 2 cytoplasmic molecules of NADH 2, depending on the shuttle mechanism, give from 4 to 6 ATP molecules in the respiratory chain of mitochondria.

Thus, the final energy effect of aerobic glycolysis, depending on the shuttle mechanism, is from 6 to 8 ATP molecules.

Anaerobic glycolysis

Under anaerobic conditions, PVC, like O 2 in the respiratory chain, ensures the regeneration of NAD + from NADH 2, which is necessary for the continuation of glycolysis reactions. PVC is then converted to lactic acid. The reaction takes place in the cytoplasm with the participation of lactate dehydrogenase.

11. Lactate dehydrogenase(lactate: NAD + oxidoreductase). Consists of 4 subunits, has 5 isoforms.

Lactate is not a metabolic end product that is removed from the body. This substance from the tissue enters the bloodstream and is utilized, turning into glucose in the liver (Cori cycle), or, when oxygen is available, it turns into PVC, which enters the general path of catabolism, oxidizing to CO 2 and H 2 O.

ATP output during anaerobic glycolysis

Anaerobic glycolysis is less efficient than aerobic glycolysis. The catabolism of 1 glucose is accompanied by the consumption of 2 ATP molecules for substrate phosphorylation, the formation of 4 ATP molecules in reactions of substrate phosphorylation, and the synthesis of 2 lactate molecules. Thus, the final energy effect of anaerobic glycolysis is equal to 2 ATP molecules.

The plastic significance of glucose catabolism

During catabolism, glucose can perform plastic functions. Glycolysis metabolites are used to synthesize new compounds. Thus, fructose-6f and 3-PGA are involved in the formation of ribose-5-f (a component of nucleotides); 3-phosphoglycerate can be included in the synthesis of amino acids such as serine, glycine, cysteine. In the liver and adipose tissue, Acetyl-CoA is used in the biosynthesis of fatty acids, cholesterol, and DAP is used for the synthesis of glycerol-3p.

Regulation of glycolysis

Pasteur effect– decrease in the rate of glucose consumption and lactate accumulation in the presence of oxygen.

The Pasteur effect is explained by the presence of competition between the enzymes of the aerobic (DG malate, glycerol-6f DG, PVA DG) and anaerobic (LDG) oxidation pathways for the common metabolite of PVA and the coenzyme NADH 2 . Without oxygen, mitochondria do not consume PVK and NADH 2, as a result, their concentration in the cytoplasm increases and they go to the formation of lactate. In the presence of oxygen, mitochondria pump out PVC and NADH2 from the cytoplasm, interrupting the lactate formation reaction. Since anaerobic glycolysis produces little ATP, there may be an excess of AMP (ADP + ADP = AMP + ATP), which, via phosphofructokinase 1, stimulates glycolysis. During aerobic catabolism of glucose, ATP is formed a lot, a possible excess of ATP through phosphofructokinase 1 and pyruvate kinase, on the contrary, inhibits glycolysis. The accumulation of glucose-6p inhibits hexokinase, which reduces the consumption of glucose by cells.

FRUCTOSE AND GALACTOSE METABOLISM

Fructose and galactose, along with glucose, are used to obtain energy or synthesize substances: glycogen, TG, GAG, lactose, etc.

Fructose metabolism

A significant amount of fructose, formed during the breakdown of sucrose, is converted into glucose already in the intestinal cells. Part of the fructose goes to the liver.

general review

The glycolytic pathway is 10 consecutive reactions, each catalyzed by a different enzyme.

The process of glycolysis can be conditionally divided into two stages. The first stage, proceeding with the energy consumption of 2 ATP molecules, is the breakdown 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 primary 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 with the help of carrier proteins. The work of these transporter proteins is controlled by hormones and, first of all, by insulin. Most of all, insulin stimulates the transport of glucose in muscle 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:

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

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

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

Way

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

For the reaction to proceed, the presence of Mg 2+ ions in the medium is necessary, with which the ATP molecule complex binds. This reaction is irreversible and is the first key reaction of glycolysis.

Phosphorylation of glucose has two goals: first, because the plasma membrane, which is permeable to a 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.

The hepatic isoenzyme of hexokinase - glucokinase - is important in the regulation of blood glucose levels.

In the next reaction ( 2 ) by the enzyme phosphoglucoisomerase G-6-P is converted into fructose-6-phosphate (F-6-F):

Energy is not required for this reaction, and the reaction is completely reversible. At this stage, fructose can also be included in the process of glycolysis by phosphorylation.

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

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

Aldol cleavage F-1,6-bF occurs under the action of fructose-1,6-bisphosphate aldolase:

As a result of the fourth reaction, dihydroxyacetone phosphate And glyceraldehyde-3-phosphate, and the first one is almost immediately under the action phosphotriose isomerase goes to the second 5 ), which is involved in further transformations:

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

Coming from 1,3-diphosphoglycerate, containing a macroergic bond in 1 position, the phosphoglycerate kinase enzyme transfers a phosphoric acid residue to the ADP molecule (reaction 7 ) - an ATP molecule is formed:

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, with an excess of ATP in the cell (and a lack of ADP), its rate 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 proceeds 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.

Since its inception F-1,6-bF only reactions proceed with the release of energy 7 And 10 where substrate phosphorylation of ADP occurs.

Further development

The ultimate fate of pyruvate and NAD∙H formed during glycolysis depends on the host and conditions within the cell, especially 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 action of the enzyme lactate dehydrogenase. In yeast, a similar process is alcoholic fermentation, where the end products will be ethanol and carbon dioxide. Butyric and citrate fermentation is also known.

Butyric fermentation:

Glucose → butyric acid + 2 CO 2 + 2 H 2 O.

Alcoholic fermentation:

Glucose → 2 ethanol + 2 CO 2.

Citric fermentation:

Glucose → citric acid + 2 H 2 O.

Fermentation is essential in the food industry.

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

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

PVC + NAD∙H + H + → lactate + NAD + .

Muscle pain that occurs some time after unusual intense physical activity is 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 end product of metabolism. Under the action of lactate dehydrogenase, lactic acid is oxidized again, forming pyruvate, which is involved in further transformations.

Regulation of glycolysis

Distinguish between local and general regulation.

Local regulation is carried out by changing the activity of enzymes under the influence of various metabolites inside the cell.

The regulation of glycolysis as a whole, immediately for the whole organism, occurs under the action of hormones, which, influencing through molecules of secondary messengers, change intracellular metabolism.

Insulin plays an important role in stimulating glycolysis. Glucagon and adrenaline are the most significant hormonal inhibitors of glycolysis.

Insulin stimulates glycolysis through:

• activation of the hexokinase reaction;
• stimulation of phosphofructokinase;
• stimulation of pyruvate kinase.

Other hormones also influence glycolysis. For example, somatotropin inhibits glycolysis enzymes, and thyroid hormones are stimulants.

Glycolysis is regulated through several key steps. Reactions catalyzed by hexokinase ( 1 ), phosphofructokinase ( 3 ) and pyruvate kinase ( 10 ) are characterized by a significant decrease in free energy and are practically irreversible, which allows them to be effective points of regulation of glycolysis.

Regulation of hexokinase

Hexokinase inhibited by the reaction product - glucose-6-phosphate, which allosterically binds to the enzyme, changing its activity.

Due to the fact that the bulk of G-6-P in the cell is produced by the breakdown of glycogen, the hexokinase reaction, in fact, is not necessary for the occurrence of glycolysis, and glucose phosphorylation in the regulation of glycolysis is not of exceptional importance. The hexokinase reaction is an important step in the regulation of glucose concentration in the blood and in the cell.

During phosphorylation, glucose loses its ability to be transported through the membrane by carrier molecules, which creates conditions for its accumulation in the cell. Inhibition of hexokinase G-6-P limits the entry of glucose into the cell, preventing its excessive accumulation.

Glucokinase (IV isotype of hexokinase) of the liver is not inhibited by glucose-6-phosphate, and liver cells continue to accumulate glucose even at a high content of G-6-P, from which glycogen is subsequently synthesized. Compared to other isotypes, glucokinase has a high value of the Michaelis constant, that is, the enzyme works at full capacity only under conditions of high glucose concentration, which occurs almost always after a meal.

Glucose-6-phosphate can be converted back to glucose by the action of glucose-6-phosphatase. The enzymes glucokinase and glucose-6-phosphatase are involved in maintaining normal blood glucose levels.

Phosphofructokinase regulation

The intensity of the phosphofructokinase reaction has a decisive effect on the entire throughput of glycolysis, and the stimulation of phosphofructokinase is considered the most important step in the regulation.

Phosphofructokinase (PFK) is a tetrameric enzyme that exists alternately in two conformational states (R and T), which are in equilibrium and alternately pass from one to another. ATP is both a substrate and an allosteric inhibitor of PFK.

Each of the FFK subunits has two ATP binding sites: a substrate site and an inhibition site. The substrate site is equally capable of attaching ATP in any tetramer conformation. Whereas the site of inhibition binds ATP exclusively when the enzyme is in the T conformational state. Another substrate for FPA is fructose 6-phosphate, which attaches to the enzyme preferably in the R state. At a high concentration of ATP, the inhibition site is occupied, transitions between enzyme conformations become impossible, and most of the enzyme molecules are stabilized in the T-state, unable to attach P-6-P. However, inhibition of ATP phosphofructokinase is suppressed by AMP, which attaches to the R-conformations of the enzyme, thus stabilizing the state of the enzyme for binding F-6-P.

The most important allosteric regulator of glycolysis and gluconeogenesis is fructose 2,6-bisphosphate, which is not an intermediate link of these cycles. Fructose-2,6-bisphosphate allosterically activates phosphofructokinase.

The synthesis of fructose-2,6-biphosphate is catalyzed by a special bifunctional enzyme - phosphofructokinase-2 / fructose-2,6-biphosphatase (FFK-2 / F-2,6-BPase). In its unphosphorylated form, the protein is known as phosphofructokinase-2 and has catalytic activity on fructose 6-phosphate, producing fructose 2-6-bisphosphate. As a result, the activity of FFK is significantly stimulated and the activity of fructose-1,6-biphosphatase is strongly inhibited. That is, under the condition of FFK-2 activity, the balance of this reaction between glycolysis and gluconeogenesis is shifted towards the first - fructose-1,6-bisphosphate is synthesized.

In the phosphorylated form, the bifunctional enzyme does not have kinase activity; on the contrary, a site is activated in its molecule that hydrolyzes P2,6BP into P6P and inorganic phosphate. The metabolic effect of phosphorylation of the bifunctional enzyme is that allosteric stimulation of PFK stops, allosteric inhibition of F-1,6-BPase is eliminated, and the equilibrium shifts towards gluconeogenesis. F6F is produced and then glucose.

Interconversions of the bifunctional enzyme are carried out by cAMP-dependent protein kinase (PC), which, in turn, is regulated by peptide hormones circulating in the blood.

When the concentration of glucose in the blood decreases, the formation of insulin is also inhibited, and the release of glucagon, on the contrary, is stimulated, and its concentration in the blood rises sharply. Glucagon (and other contrainsular hormones) bind to receptors on the plasma membrane of liver cells, causing activation of membrane adenylate cyclase. Adenylate cyclase catalyses the conversion of ATP to cyclic AMP. cAMP binds to the regulatory subunit of protein kinase, causing the release and activation of its catalytic subunits, which phosphorylate a number of enzymes, including the bifunctional FFK-2/P-2,6-BPase. At the same time, glucose consumption in the liver stops and gluconeogenesis and glycogenolysis are activated, restoring normoglycemia.

pyruvate kinase

The next step, where the regulation of glycolysis is carried out, is the last reaction - the stage of action of pyruvate kinase. For pyruvate kinase, a number of isoenzymes have also been described that have regulatory features.

Hepatic pyruvate kinase(L-type) is regulated by phosphorylation, by allsteric effectors and by regulation of gene expression. The enzyme is inhibited by ATP and acetyl-CoA and activated by fructose-1,6-bisphosphate. Inhibition of ATP pyruvate kinase occurs similarly to the action of ATP on PFK. The binding of ATP to the site of enzyme inhibition reduces its affinity for phosphoenolpyruvate. Hepatic pyruvate kinase is phosphorylated and inhibited by protein kinase, and is thus also under hormonal control. In addition, the activity of hepatic pyruvate kinase is also regulated quantitatively, that is, by changing the level of its synthesis. This is a slow, long-term regulation. An increase in carbohydrates in the diet stimulates the expression of genes encoding pyruvate kinase, as a result, the level of the enzyme in the cell increases.

M-type pyruvate kinase found in brain, muscle and other glucose-demanding tissues is not regulated by protein kinase. This is fundamental in that the metabolism of these tissues is determined only by internal needs and does not depend on the level of glucose in the blood.

Muscle pyruvate kinase is not subject to external influences, such as lowering blood glucose levels or hormonal release. Extracellular conditions that lead to phosphorylation and inhibition of the hepatic isoenzyme do not alter the activity of M-type pyruvate kinase. That is, the intensity of glycolysis in striated muscles is determined only by the conditions inside the cell and does not depend on the general regulation.

Meaning

Glycolysis is a catabolic pathway of exceptional importance. It provides energy for cellular reactions, including protein synthesis. The intermediate products of glycolysis are used in the synthesis of fats. Pyruvate can also be used to synthesize alanine, aspartate, and other compounds. Thanks to glycolysis, mitochondrial performance and oxygen availability do not limit muscle power during short-term extreme loads.

see also

Links

• glycolysis (English)

Wikimedia Foundation. 2010 .

To understand what glycolysis is, you will have to turn to Greek terminology, because this term comes from the Greek words: glycos - sweet and lysis - splitting. From the word Glycos comes the name of glucose. Thus, this term refers to the process of saturation of 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 types of glucose breakdown, 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 essence of glycolysis. The released energy is spent on the general vital activity of a living organism. The general formula for glucose breakdown looks like this:

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

Aerobic oxidation of glucose, followed by cleavage of its six-carbon molecule, is carried out through 10 intermediate reactions. The first 5 reactions are combined by the preparatory phase of preparation, and subsequent reactions are aimed at the formation of ATP. During the reactions, stereoscopic isomers of sugars 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

In aerobic glycolysis, 2 phases are distinguished.

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

1st step. Phosphorylation of glucose

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

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 reactions of glycolysis.

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

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

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

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

3rd step. Phosphorylation of fructose-6-phosphate

At this stage, the addition of a phosphoryl group occurs due to ATP. The process is carried out with the participation of the enzyme phosphofructokinase-1. This enzyme is intended only for participation in hydrolysis. As a result of the reaction, fructose-1,6-bisphosphate and nucleotide adesine triphosphate are obtained.

ATP - 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. Hydrolysis of ATP is accompanied by the formation of phosphoric acid and the release of 40-60 J of energy that the body spends on its vital activity.

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

4th step. The breakdown of fructose-1,6-diphosphate

In the fourth reaction, fructose-1,6-diphosphate decomposes into two new substances.

• dihydroxyacetone phosphate,
• Glyceraldehyde-3-phosphate.

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

5th step. Formation of triose phosphate isomers

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

Glycerald-3-phosphate will continue to participate in the process of aerobic hydrolysis. And the second component, dihydroxyacetone phosphate, with the participation of the enzyme triose phosphate isomerase, is converted into glyceraldehyde-3-phosphate. 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. It also produces NADH.

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. restored (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 a living organism, NAD is produced from tryptophan or amino acid aspartate.

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

6th step - oxidation of glyceraldehyde-3-phosphate

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

The reaction occurs with the participation of energy received from outside, therefore it is called endergonic. Such reactions proceed in parallel with exergonic, that is, releasing, giving off energy. In this case, such a reaction is the following process.

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

In this intermediate reaction, a 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 in it 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'o \u003d -12.2 kJ / mol.

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

8th step. Transfer of a phosphoryl group from 3-phosphoglycerate.

Obtaining 2-phosphoglycerate is a reversible process, 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 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 step. Isolation of water from 2-phosphoglycerate

This reaction is essentially the second reaction of glucose breakdown (the first was the reaction of the 6th step). In it, the enzyme phosphopyruvate hydratase stimulates the elimination 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 last step. Transfer of a phosphate residue from PEP to ADP

The final reaction of glycolysis involves coenzymes - potassium, magnesium and manganese, 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 transition of 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 consecutive reactions. But where does the anaerobic stage of glycolysis take place, 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 in the process of 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 of 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 there are no mitochondria in blood cells.

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. Oxygen is needed for oxidative processes, but it is not present in anaerobic glycolysis.

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 starts again. The lack of glucose is replenished by nutrition - the use of sugar, sweet fruits, and other sweets. So you can’t completely refuse sweets for the sake of the figure. The body needs sucrose, but in moderation.