The process of primary synthesis of glucose takes place in. The body is able to synthesize glucose. Significance of anaerobic glycolysis

Gluconeogenesis is the synthesis of glucose from non-carbohydrate compounds.

In the body of an adult, up to 250 g of glucose can be synthesized per day. Gluconeogenesis is carried out mainly in the liver (synthesizing up to 90% of all glucose), in the cortex of the kidneys and in enterocytes (very insignificantly).

Gluconeogenesis is stimulated during prolonged fasting, when the intake of carbohydrates from food is limited, during the recovery period after muscle load, in newborns in the first hours after birth.

Gluconeogenesis substrates. The true substrates of gluconeogenesis are pyruvate, oxaloacetate, phosphodoxyacetone, which are directly involved in this process. All substances of a non-carbohydrate nature that give these metabolites are substrates for gluconeogenesis: lactate → PVC, metabolites of the Krebs cycle → PAK, glycerol → phosphodioxyacetone, propionyl-CoA → metabolites of the Krebs cycle → PAA, glucogenic amino acids → PVA or PAA. The main source of substrates for gluconeogenesis is glucogenic amino acids. Glucogenic amino acids include all proteinogenic amino acids, except for leucine and lysine.

Stoichiometry:

2PVK + 4ATP + 2GTP + 2NADH + + 2H + 6H2O Glucose + 4ADP + 2GDF + 6Fn + 2NAD +

Gluconeogenesis proceeds mainly along the same path as glycolysis, but in the opposite direction. Four specific gluconeogenesis enzymes are used to bypass three key glycolysis reactions.
Key enzymes and key reactions of gluconeogenesis:

1. Pyruvate carboxylase
2. Phosphoenolpyruvate carboxykinase
3. Fructose-1,6-bisphosphatase (Fructose-1,6-bisphosphate + H2O and Fructose-6-phosphate + FN)
4. Glucose-6-phosphatase (Glucose-6-phosphate + H2O and Glucose + FN)

Energy balance. For the synthesis of a glucose molecule from two pyruvate molecules, 4ATP and 2GTP (6ATP) are consumed. Energy for gluconeogenesis is supplied by the β-oxidation of fatty acids.

Regulation of gluconeogenesis. Gluconeogenesis is stimulated in hypoglycemic conditions with low insulin levels and a predominance of its antagonists (glucagon, catecholamines, glucocorticoids).

1. Regulation of the activity of key enzymes:

fructose-1,6-bisphosphatase by the allosteric mechanism is activated by ATP, inhibited by Fr-1,6-PF and AMP;

pyruvate carboxylase is activated by CH3CO ~ CoA (allosteric activator).

2. Regulation of the amount of key enzymes: glucocorticoids and glucagon

induce the synthesis of key enzymes, and insulin represses.

3. Regulation of the amount of substrate: the amount of substrates of gluconeogenesis increases under the action of glucocorticoids (catabolic effect on proteins of muscle and lymphoid tissue, on adipose tissue), as well as glucagon (catabolic effect on adipose tissue).

The biological role of gluconeogenesis:

1. Maintaining blood glucose levels. With prolonged fasting (fasting for more than a day), gluconeogenesis is the only process that supplies glucose to the blood.

2. Return of lactate to the metabolic pool of carbohydrates. Lactate, formed during the anaerobic oxidation of glucose in erythrocytes and skeletal muscles, is transported by the blood to the liver and converted into glucose in hepatocytes. This is the so-called interorgan Corey cycle.

In pyruvate or one of the intermediate products of the tricarboxylic acid cycle.

In vertebrates, gluconeogenesis occurs most intensively in the cells of the liver and kidneys (in the cortex).

The first stage of synthesis takes place in the mitochondria (Fig. 10.6). Pyruvate carboxylase, which catalyzes this reaction, is an allosteric mitochondrial enzyme. Acetyl-CoA is required as an allosteric activator of this enzyme. The mitochondrial membrane is impermeable to the formed oxaloacetate. The latter here, in the mitochondria, is reduced to malate:

Further conversion of oxaloacetate to phosphoenolpyruvate occurs in the cell cytosol.

Conversion of fructose-1,6-bisphosphate to fructose-6-phosphate... Phospho-enolpyruvate, formed from pyruvate, is converted into fructose-1,6-bisphosphate as a result of a series of reversible glycolysis reactions. This is followed by the phosphofructokinase reaction, which is irreversible. Gluconeogenesis bypasses this endergonic reaction. The conversion of fructose-1,6-bis-phosphate to fructose-6-phosphate is catalyzed by a specific phosphatase:

Figure: 10.6.Formation of phosphoenol pyruvate from pyruvate. 1 - pyruvate carboxylase; 2 - malate dehydrogenase (mitochondrial); 3-malate dehydrogenase (cytoplasmic); 4 - phosphoenolpyruvate carboxy kinase.

Another important point in the regulation of gluconeogenesis is the reaction catalyzed by fructose-1,6-bisphosphatase, an enzyme that is inhibited by AMP. AMP has the opposite effect on phosphofructokinase, i.e. for this enzyme it is an allosteric activator. With a low concentration of AMP and a high level of ATP, gluconeogenesis is stimulated. On the contrary, when the value of the ATP / AMP ratio is small, glucose breakdown is observed in the cell.

In 1980, a group of Belgian researchers (G. Hers et al.) Discovered fructose-2,6-bisphosphate in the liver tissue, which is a powerful regulator of the activity of the two listed enzymes:

Fructose-2,6-bisphosphate activates phosphofructokinase and inhibits fructose-1,6-bisphosphatase. An increase in the level of fructose-2,6-bis-phosphate in the cell promotes increased glycolysis and a decrease in the rate of gluconeogenesis. With a decrease in the concentration of fructose-2,6-bisphosphate, the opposite picture is observed.

It was also shown that the bifunctional enzyme, in turn, is regulated by cAMP-dependent phosphorylation. Phosphorylation leads to an increase in phosphatase activity and a decrease in the phosphokinase activity of a bifunctional enzyme. This mechanism explains the rapid effect of hormones, in particular glucagon, on the level of fructose-2,6-bisphosphate in the cell (see Chapter 16).

The activity of the bifunctional enzyme is also regulated by some

49. Simplified scheme of starch and glycogen hydrolysis in an animal organism.
50. Glycolysis and its main stages. Significance of glycolysis.

Essence, total reactions and efficiency of glycolysis.

The role of carbohydrate metabolism. Sources of glucose and ways of using it in the body.

The main role of carbohydrates is determined by their energy function.

Glucose (from ancient Greek γλυκύς sweet) (C 6 H 12 O 6) or grape sugar is a white or colorless odorless substance with a sweet taste, soluble in water. Cane sugar is about 25% sweeter than glucose. Glucose is the most important carbohydrate for humans. In humans and animals, glucose is the main and most versatile source of energy for metabolic processes. Glucose is deposited in animals in the form of glycogen, in plants - in the form of starch.

Sources of glucose
Under normal conditions, food carbohydrates are the main source of carbohydrates for humans. The daily requirement for carbohydrates is approximately 400 g. In the process of assimilation of food, all exogenous polymers of carbohydrate nature are broken down into monomers, only monosaccharides and their derivatives enter the internal environment of the body from the intestine.

Blood glucose is a direct source of energy in the body. The rapidity of its decay and oxidation, as well as the possibility of rapid extraction from the depot, provide an emergency mobilization of energy resources with rapidly increasing energy consumption in cases of emotional excitement, with intense muscle stress, etc.
The blood glucose level is 3.3-5.5 mmol / l (60-100 mg%) and is the most important homeostatic constant in the body. The central nervous system is especially sensitive to a decrease in blood glucose levels (hypoglycemia). Minor hypoglycemia is manifested by general weakness and rapid fatigue. With a decrease in blood glucose to 2.2-1.7 mmol / l (40-30 mg%), convulsions, delirium, loss of consciousness develop, as well as autonomic reactions: increased sweating, changes in the lumen of skin vessels, etc. the name "hypoglycemic coma". The introduction of glucose into the blood quickly eliminates these disorders.

The energetic role of glucose.

1. Cells use glucose as an energy source. The main part of glucose, after going through a series of transformations, is spent on the synthesis of ATP in the process of oxidative phosphorylation. More than 90% of carbohydrates are consumed for energy production during glycolysis.

2. An additional way of energy use of glucose - without the formation of ATP. This path is called pentose phosphate. In the liver, it is about 30% of the conversion of glucose, in fat cells - slightly more. This energy is spent for the formation of NADP, which serves as a donor of hydrogen and electrons necessary for synthetic processes - the formation of nucleic and bile acids, steroid hormones.

3. The conversion of glucose into glycogen or fat occurs in liver cells and adipose tissue. When carbohydrate stores are low, for example, under stress, gluneogenesis develops - the synthesis of glucose from amino acids and glycerol.

The scheme of using glucose in the body

The metabolism of carbohydrates in the human body consists of the following processes:

1. Splitting in the digestive tract of poly- and disaccharides coming from food to monosaccharides, further absorption of monosaccharides from the intestine into the blood.

2. Synthesis and breakdown of glycogen in tissues (glycogenesis and glycogenolysis), primarily in the liver.

Glycogen - the main form of glucose deposition in animal cells. In plants, starch performs the same function. Structurally, glycogen, like starch, is a branched polymer of glucose. However, glycogen is more branched and more compact. Branching allows the rapid release of a large number of terminal monomers during the breakdown of glycogen.

The role of glycogen:

Is the main form of glucose storage in animal cells

Forms an energy reserve that can be quickly mobilized if necessary to replenish a sudden lack of glucose

It is deposited in the form of granules in the cytoplasm in many types of cells (mainly liver and muscles)

Only the glycogen stored in liver cells can be converted into glucose to feed the entire body. The total mass of glycogen in the liver can reach 100-120 grams in adults

Liver glycogen is never completely broken down

In muscles, glycogen is converted to glucose-6-phosphate, exclusively for local consumption. No more than 1% of the total muscle mass accumulates in the muscles of glycogen

A small amount of glycogen is found in the kidneys, and even less in glial cells of the brain and leukocytes

Synthesis and breakdown of glycogen are not turning into each other, these processes occur in different ways.

The glycogen molecule contains up to 1 million glucose residues, therefore, a significant amount of energy is spent on synthesis. The need to convert glucose into glycogen is due to the fact that the accumulation of a significant amount of glucose in the cell would lead to an increase in osmotic pressure, since glucose is a highly soluble substance. On the contrary, glycogen is contained in the cell in the form of granules, and is slightly soluble.

Glycogen synthesis:

Glycogen is synthesized during digestion (within 1-2 hours after ingestion of carbohydrate food). Glycogenesis is especially intense in the liver and skeletal muscles.

To include 1 glucose residue in the glycogen chain, 1 ATP and 1 UTP are spent

The main activator is the hormone INSULIN

Breakdown of glycogen:

It is activated in the intervals between meals and during physical work, when the level of glucose in the blood decreases (relative hypoglycemia)

The main activators of decay:

in the liver - the hormone GLUCAGON

in the muscles - the hormone ADRENALINE

Simplified scheme of starch and glycogen hydrolysis in an animal body.

3. Pentose phosphate pathway (pentose cycle) is an anaerobic pathway for the direct oxidation of glucose.

No more than 25-30% of glucose entered the cells goes along this path

The final equation of the pentose phosphate pathway:

6 glucose molecules + 12 NADPH → 5 glucose molecules + 6 CO2 + 12 NADPH2

The biological role of the pentose phosphate pathway in an adult, it consists in performing two important functions:

· He is a supplier of pentoses, which are necessary for the synthesis of nucleic acids, coenzymes, macroergs for plastic purposes.

Serves as a source of NADPH2, which, in turn, is used for:

1.reductive synthesis of steroid hormones, fatty acids

2. actively participates in the neutralization of toxic substances in the liver

4. Glycolysis - breakdown of glucose. Initially, this term meant only anaerobic fermentation, which ends with the formation of lactic acid (lactate) or ethanol and carbon dioxide. Currently, the term "glycolysis" is used more widely to describe the breakdown of glucose, passing through the formation of glucose-6-phosphate, fructose diphosphate and pyruvate, both in the absence and in the presence of oxygen. In the latter case, the term "aerobic glycolysis" is used, in contrast to "anaerobic glycolysis", resulting in the formation of lactic acid or lactate.

GLYCOLYSIS

A small, uncharged glucose molecule is capable of leaving the cell by diffusion. In order for glucose to remain in the cell, it must be converted to a charged form (usually glucose-6-phosphate). This reaction is called blocking, or blocking.

Further ways of using glucose-6-phosphate in cells:

Glycolysis and complete aerobic oxidation of glucose

Pentose phosphate cycle (partial oxidation of glucose to pentoses)

Glycogen synthesis, etc.

Glycolysisoccurs in the cytoplasm of cells. The end product of this stage is pyruvic acid.

ANAEROBIC GLYCOLYSIS - the process of splitting glucose with the formation of the final product lactate through pyruvate. It proceeds without the use of oxygen and therefore does not depend on the functioning of the mitochondrial respiratory chain.

Leaks in the muscles when performing intense loads, in the first minutes of muscle work, in erythrocytes (in which mitochondria are absent), as well as in various organs under conditions of a limited supply of oxygen, including in tumor cells. This process serves as an indicator of an increased rate of cell division with an insufficient supply of them with a blood vessel system.

Stages of glycolysis.

1. Preparatory stage (takes place with the consumption of two ATP molecules)

Glucose + 2ATP → glucose-6-phosphate → fructose-1,6-diphosphate

Enzymes: glucokinase; phosphofructoisomerase;

2. Stage of formation of triose (splitting glucose into 2 three-carbon fragments)

Fructose-1,6-diphosphate → 2 glyceroaldehyde-3-phosphate

3. Oxidative stage of glycolysis (gives 4 moles of ATP per 1 mole of glucose)

2 glyceroaldehyde-3-phosphate + 2NAD + → 2 PVC + 2 ATP

2 PVC + 2 NADH * H + → 2 lactate + 2NAD +

2 OVER gives 6 ATP

This method of ATP synthesis, which is carried out without the participation of tissue respiration and, therefore, without oxygen consumption, provided with a supply of substrate energy, is called anaerobic, or substrate, phosphorylation .

This is the fastest way to get ATP. It should be borne in mind that at the first stages, two ATP molecules are consumed for the activation of glucose and fructose-6-phosphate. As a result, the conversion of glucose to pyruvate is accompanied by the synthesis of eight ATP molecules.

The general equation for glycolysis looks like this:

Glucose + O2 + 8ADP + 8H 3 RO 4 → 2 Pyruvate + 2H2O + 8 ATP,

Glycolysis value:

1. Glycolysis is a mitochondria-independent way of obtaining ATP in the cytoplasm (2 mol of ATP per mol of glucose). Basic physiological significance - the use of energy that is released in this process for the synthesis of ATP. Glycolysis metabolites are used to synthesize new compounds (nucleosides; amino acids: serine, glycine, cysteine).

2. If glycolysis proceeds to lactate, then in the process there is a "regeneration" of NAD + without the participation of tissue respiration

3. In cells that do not contain mitochondria (erythrocytes, sperm), glycolysis is the only way to synthesize ATP

4. In case of poisoning of mitochondria with carbon monoxide and other respiratory poisons, glycolysis allows you to survive

Regulation of glycolysis:

1. The rate of glycolysis decreases if glucose does not enter the cell (regulation by the amount of substrate), but soon the breakdown of glycogen begins and the rate of glycolysis is restored

2. AMP (low energy signal)

3. Regulation of glycolysis by hormones. Stimulates glycolysis: Insulin, Adrenaline (stimulates the breakdown of glycogen; in this case, glucose-6 phosphate is formed in the muscles and glycolysis is activated by the substrate). Inhibits glycolysis: Glucagon (represses the pyruvate kinase gene; converts pyruvate kinase into an inactive form)

The meaning of anaerobic glycolysis in brief

• Under conditions of intense muscular work, with hypoxia (for example, an intense run at 200m for 30 s), the breakdown of carbohydrates temporarily occurs under anaerobic conditions
• NADH molecules cannot give up their hydrogen, since the respiratory chain in mitochondria "does not work"
• Then, in the cytoplasm, a good hydrogen acceptor is pyruvate- the end product of the 1st stage
• At rest, which occurs after intense muscle work, oxygen begins to flow into the cell
• This leads to the "start" of the respiratory chain
• As a result, anaerobic glycolysis is inhibited automatically and switches to aerobic, more energetically beneficial
• The inhibition of anaerobic glycolysis by oxygen entering the cell is called PASTER EFFECT

PASTER EFFECT. It consists in respiratory depression (O 2) of anaerobic glycolysis, i.e. there is a switch from aerobic glycolysis to anaerobic oxidation. If the tissues are supplied with O 2, then 2NADH 2, formed during the central oxidoreduction reaction, will be oxidized in the respiratory chain; therefore, PVC does not convert to lactate, but to acetyl-CoA, which is involved in CTX.

The first stage in the breakdown of carbohydrates is anaerobic glycolysis - practically reversible. From pyruvate, as well as from lactate (lactic acid) arising under anaerobic conditions, glucose can be synthesized, and from it glycogen.

The similarity between anaerobic and aerobic glycolysis lies in the fact that, prior to the stage of PVC formation, these processes proceed in the same way with the participation of the same enzymes.

TOTAL AEROBIC OXIDATION OF GLUCOSE (PAOG):

Thanks to the activity of mitochondria, it is possible to completely oxidize glucose to carbon dioxide and water.

In this case, glycolysis is the first step in the oxidative metabolism of glucose.

Before incorporating mitochondria into PAOG, glycolytic lactate should be converted to PVC.

The main stages of PAOG:

1. Glycolysis followed by the conversion of 2 mol of lactate into 2 mol of PVC and the transport of protons to mitochondria

2. Oxidative decarboxylation of 2 mol of pyruvate in mitochondria with the formation of 2 mol of acetylCoA

3. Combustion of the acetyl residue in the Krebs cycle (2 revolutions of the Krebs cycle)

4. Tissue respiration and oxidative phosphorylation: NADH * H + and FADH2 are used, generated in the Krebs cycle, oxidative decarboxylation of pyruvate and transferred by a malate shuttle from the cytoplasm

Stages of catabolism on the example of PAOG :

Glycolysis, transport of protons into mitochondria (stage I),

Oxidative decarboxylation of pyruvate (stage II)

Krebs cycle - stage III

Tissue respiration and associated oxidative phosphorylation - stage IV (mitochondrial ATP synthesis)

II. During the second phase carbon dioxide and two hydrogen atoms are split off from pyruvic acid. The split-off hydrogen atoms along the respiratory chain are transferred to oxygen with the simultaneous synthesis of ATP. Acetic acid is formed from pyruvate. It joins a special substance, coenzyme A.

This substance is a carrier of acid residues. The result of this process is the formation of the substance acetyl coenzyme A. This substance has high chemical activity.

The final equation of the second stage:

СЗН4ОЗ + 1 / 2О2 + HSKoA + 3 ADP + 3 НзРО4 - СН3- С ~ SKoA + СО2 + Н2О + 3ATP

Pyruvate Coenzyme A Acetyl-CoA

Acetyl coenzyme A undergoes further oxidation in the tricarboxylic acid cycle (Krebs cycle) and is converted into CO2 and H2O.

III. This is the third stage.... Due to the released energy at this stage, ATP synthesis is also carried out.

Tricarboxylic acid cycle (TCA) - this is the final stage of catabolism not only of carbohydrates, but also of all other classes of organic compounds. This is due to the fact that during the breakdown of carbohydrates, fats and amino acids, a common intermediate product is formed - acetic acid, associated with its carrier - co-fermeng A - in the form of acetyl coenzyme A.

The Krebs cycle takes place in mitochondria with mandatory oxygen consumption and requires the functioning of tissue respiration.

The first reaction of the cycle is the interaction of acetyl coenzyme A with oxalic-acetic acid (ABA) to form citric acid.

Citric acid contains three carboxyl groups, that is, it is a tricarboxylic acid, which gave rise to the name of this cycle.

Therefore, these reactions are called the citric acid cycle. Forming a series of intermediate tricarboxylic acids, citric acid is again converted to oxalic-acetic acid and the cycle repeats. The result of these reactions is the formation of split-off hydrogen, which, passing through the respiratory chain, forms water with oxygen. The transfer of each pair of hydrogen atoms to oxygen is accompanied by the synthesis of three ATP molecules. In total, during the oxidation of one molecule of acetyl coenzyme A, 12 ATP molecules are synthesized.

The final equation of the Krebs cycle (third stage):

СН3- С ~ SKoA + 2О2 + Н2О + 12ADP + 12 Н3РО → НSKoA + 2 СО2 + Н2О + 12АТФ

The Krebs cycle can be schematically represented as follows:

As a result of all these reactions, 36 ATP molecules are formed. In total, glycolysis gives 38 ATP molecules per one glucose molecule.

Glucose + 6 О2 + 38 ADP + 38 Н3 РО4 → 6СО2 + 6 Н2О +38 ATP

The biological role of TCA

The Krebs cycle plays an integrative, amphibolic (i.e. catabolic and anabolic), energetic and hydrogen-donor role.

1. The integration role is that TCA is the final common pathway for the oxidation of fuel molecules - carbohydrates, fatty acids and amino acids.

2. Acetyl-CoA is oxidized in the TCA - this is a catabolic role.

3. The anabolic role of the cycle is that it supplies intermediates for biosynthetic processes. For example, oxaloacetate is used for the synthesis of aspartate, a-ketoglutarate for the formation of glutamate, and succinyl-CoA for the synthesis of heme.

4. One ATP molecule is formed in the TCA at the level of substrate phosphorylation - this is an energetic role.

5. Hydrogen-donor consists in the fact that CTK provides reduced coenzymes NADH (H +) and FADH2 to the respiratory chain, in which the hydrogen of these coenzymes is oxidized to water, coupled with the synthesis of ATP. During the oxidation of one acetyl-CoA molecule in CTK 3 NADH (H +) and 1 FADH2 are formed

Stage IV. Tissue respiration and associated oxidative phosphorylation (mitochondrial ATP synthesis)

This is the transfer of electrons from reduced nucleotides to oxygen (through the respiratory chain). It is accompanied by the formation of the final product - a water molecule. This electron transport is associated with the synthesis of ATP during oxidative phosphorylation.

Oxidation of organic matter in cells, accompanied by the consumption of oxygen and the synthesis of water, is called tissue respiration, and the electron transport chain (CPE) - respiratory chain.

Features of biological oxidation:

1.Leaks at body temperature;

2. In the presence of H2O;

3. Proceeds gradually through numerous stages with the participation of carrier enzymes that reduce the activation energy, a decrease in free energy occurs, as a result of which the energy is released in portions. Therefore, oxidation is not accompanied by an increase in temperature and does not lead to an explosion.

The electrons entering the CPE, as they move from one carrier to another, lose free energy. Much of this energy is stored in ATP, and some is dissipated as heat.

The transfer of electrons from oxidized substrates to oxygen occurs in several stages. It involves a large number of intermediate carriers, each of which is able to attach electrons from the previous carrier and transfer to the next. This is how a chain of redox reactions arises, resulting in the reduction of O2 and the synthesis of H2O.

The transport of electrons in the respiratory chain is conjugated (connected) with the formation of a proton gradient, which is necessary for the synthesis of ATP. This process is called oxidative phosphorylation... In other words, oxidative phosphorylation is a process in which the energy of biological oxidation is converted into the chemical energy of ATP.

Respiratory circuit function - utilization of reduced respiratory carriers formed in the reactions of metabolic oxidation of substrates (mainly in the tricarboxylic acid cycle). Each oxidative reaction, in accordance with the amount of released energy, is "served" by the corresponding respiratory carrier: NADP, NAD or FAD. In the respiratory chain, protons and electrons are discriminated against: while protons are transported across the membrane, creating ΔpH, electrons move along the carrier chain from ubiquinone to cytochrome oxidase, generating the electrical potential difference necessary for the formation of ATP by proton ATP synthase. Thus, tissue respiration "charges" the mitochondrial membrane, and oxidative phosphorylation "discharges" it.

RESPIRATORY CONTROL

The transfer of electrons along the CPE and the synthesis of ATP are closely coupled, i.e. can only occur simultaneously and synchronously.

With an increase in the consumption of ATP in the cell, the amount of ADP and its entry into mitochondria increase. Increasing the concentration of ADP (a substrate of ATP synthase) increases the rate of ATP synthesis. Thus, the rate of ATP synthesis exactly matches the energy requirement of the cell. Acceleration of tissue respiration and oxidative phosphorylation with an increase in the concentration of ADP is called respiratory control.

In CPE reactions, part of the energy is not converted into the energy of high-energy ATP bonds, but is dissipated in the form of heat.

The difference in electrical potential across the mitochondrial membrane, created by the respiratory chain, which acts as a molecular conductor of electrons, is the driving force for the production of ATP and other types of useful biological energy. This concept of energy conversion in living cells was put forward by P. Mitchell in 1960 to explain the molecular mechanism of conjugation of electron transport and the formation of ATP in the respiratory chain and quickly gained international recognition. In 1978 P. Mitchell was awarded the Nobel Prize for the development of research in the field of bioenergy. In 1997, P. Boyer and J. Walker were awarded the Nobel Prize for elucidating the molecular mechanisms of action of the main enzyme of bioenergetics, proton ATP synthase.

Calculation of the energy yield of PAOG by stages:

Glycolysis - 2 ATP (substrate phosphorylation)

Transfer of protons into mitochondria - 2 NADH * H + \u003d 6 ATP

Oxidative decarboxylation of 2 mol PVCA - 2 NADH * H + \u003d 6 ATP

Krebs cycle (taking into account TD and RP) - 12 * 2 \u003d 24 mol of ATP during combustion of 2 acetyl residues

TOTAL: 38 mol of ATP with complete combustion of 1 mol of glucose

Glycolysis value:

1) carries out a connection between respiratory substrates and the Krebs cycle;

2) supplies two ATP molecules and two NADH molecules for the needs of the cell during the oxidation of each glucose molecule (under anoxia conditions, glycolysis, apparently, is the main source of ATP in the cell);

3) produces intermediates for synthetic processes in the cell (for example, phosphoenolpyruvate, which is necessary for the formation of phenolic compounds and lignin);

4) in chloroplasts, it provides a direct pathway for the synthesis of ATP, independent of the supply of NADPH; in addition, through glycolysis in chloroplasts, the stored starch is metabolized into trioses, which are then exported from the chloroplast.

The glycolysis efficiency is 40%.

5. Interconversion of hexoses

6. Gluconeogenesis - the formation of carbohydrates from non-carbohydrate products (pyruvate, lactate, glycerol, amino acids, lipids, proteins, etc.).

Similar information.

And the liver. Between meals, prolonged fasting or intense physical exertion, the supply of glucose can be depleted, therefore there is a metabolic pathway for gluconeogenesis, which ensures its formation from non-hydrocarbon precursors such as pyruvate and related tri- or chotiricarbon compounds. Gluconeogenesis is an energy-intensive process.

The metabolic pathway of gluconeogenesis is present in representatives of all major groups of living nature: bacteria, archaea, plants, fungi and animals. The reactions of gluconeogenesis are the same in all organisms in all tissues, but its metabolic context may differ.

Gluconeogenesis provides for the synthesis of glucose from pyruvate, and glycolysis, on the contrary, breaks down glucose to pyruvate, but gluconeogenesis is not the reverse copy of glycolysis, although many reactions (seven out of ten) are common to both pathways. Three glycolysis reactions are very ergonomic (i.e., have a large negative change in free energy) and irreversible in living cells: the conversion of glucose to glucose-6-phosphate, the conversion of fructose-6-phosphate to fructose-1, 6-bisphosphate, and the conversion of phosphoenolpyruvate ( FEP) to pyruvate (see glycolysis). In gluconeogenesis, there are shunts for these reactions, which also have a large negative change in free energy. Thus, both pathways - glycolysis and gluconeogenesis - are irreversible in the cell.

1. Localization and meaning

Gluconeogenesis occurs in the cells of bacteria, archaeobacteria, fungi, plants and animals. Like glycolysis, almost all transformations of gluconeogenesis are localized in the cytoplasm; however, in eukaryotes, the first reaction of this pathway takes place in the mitochondria.

In animals, the most important glucose precursors are tricarbon compounds such as pyruvate, lactate, glycerol and some amino acids. In mammals, gluconeogenesis occurs most intensively in the liver, and also, to some extent, in the cortex of the kidneys and the epithelium of the small intestine. Up to 80 g of glucose is synthesized in the human body per day. After physical exertion, lactic acid is formed in skeletal muscles, blood is transferred to the liver, where it is converted into glucose, which is transported back to the muscles and serves there as a substrate for glycogen synthesis. This metabolic pathway is called the measles cycle. Gluconeogenesis is of particular importance during fasting. so by the method of isotope labeling it was shown that at 22 hours of abstinence from food, it provides 64% of all glucose in the blood, and at 46 hours this figure approaches 100%.

Gluconeogenesis also occurs intensively in the seed, which germinates and is part of the pathway that converts storage lipids and proteins into disaccharides (mainly sucrose), which can be transported to all tissues of the young plant. Photoautotrophs also need gluconeogenesis to convert the primary products of photosynthesis to glucose. The latter is necessary for plants for the synthesis of the cell wall and as a precursor of nucleotides, coenzymes and many other substances.

Many microorganisms begin gluconeogenesis from dicarboxylic and tricarboxylic compounds found in the environment where they live, such as acetate, lactate, propionate.

2. Reactions of gluconeogenesis

Seven reactions of gluconeogenesis are inverse to the reactions of glycolysis. The energy barrier of three irreversible glycolytic reactions is overcome in gluconeogenesis by workarounds, these include: the synthesis of phosphoenolpyruvate from pyruvate, the conversion of fructose-1, 6-bisphosphate to fructose-6-phosphate, and the conversion of glucose-6-phosphate to glucose. This organization of opposite metabolic pathways not only allows both to be thermodynamically advantageous under the same conditions, but also makes it possible to resolve their regulation.

2.1. Synthesis of phosphoenolpyruvate from pyruvate

The last reaction of glycolysis - the conversion of phosphoenolpyruvate to pyruvate with simultaneous phosphorylation of ADP - has a large negative change in free energy and is irreversible. In gluconeogenesis, the opposite transformation (pyruvate to phosphoenolpyruvate) occurs in a roundabout way, consisting of at least two reactions, and in eukaryotes it requires enzymes of both mitochondria and cytoplasm. The course of this stage differs depending on whether pyruvate or lactate is a precursor in glucose synthesis.

Pyruvate is first converted to oxaloacetate by carboxylation with pyruvate carboxylase. This enzyme uses biotin as a coenzyme; the reaction is accompanied by the hydrolysis of one ATP molecule. Biotin acts as a carrier of bicarbonate and is pre-activated by the formation of a mixed anhydride (carboxyphosphate) due to the transfer of a phosphate group from ATP. Reaction equation:

Pyruvate + ATP + HCO - 3 → oxaloacetate + ADP + F n;

The carboxylation reaction is required for the metabolic activation of pyruvate.

The next reaction - simultaneous decabroxylation and phosphorylation of oxaloacetate - is catalyzed by the enzyme phosphoenolpyruvate carboxykinase, which requires the presence of Mg 2 + and GTP ions as a phosphate group donor. The product of this reaction is phosphoenolpyruvate, which is the opposite of cellular conditions.

Oxaloacetate + GTP → phosphoenolpyruvate + HDF + CO 2;

The overall equation of the process:

Pyruvate + ATP + GTP + HCO - 3 → Phosphoenolpyruvate + ADP + HDF + F n + CO 2, ΔG 0 \u003d 0.9 kJ / mol.

Thus, for the conversion of pyruvate to phosphoenolpyruvate, the hydrolysis of two nucleotide triphosphate molecules is necessary, while the opposite process in glycolysis allows the synthesis of only one ATP molecule. Although the standard change in free energy for the overall process is 0.9 kJ / mol, in real conditions, due to the very low concentration of phosphoenolpyruvate, ΔG \u003d -25 kJ / mol, i.e. the transformation is strongly eczergonic and irreversible.

2.1.1. Oxaloacetate shuttle transport

The retention of oxaloacetate is the so-called anaplerotic reaction of the tricarboxylic acid cycle, that is, one that maintains a sufficient level of its metabolites. Therefore, like the TCA itself, it occurs in the mitochondrial matrix; pyruvate carboxylase is exclusively a mitochondrial enzyme in eukaryotes. But the localization of PMT-carboxykinase differs in different organisms: in the liver of mice and rats, it is contained only in the cytosol, in rabbits and pigeons - only in mitochondria, and in humans and guinea pigs it is approximately equally distributed between the two compartments. The rest of the enzymes of gluconeogenesis is cytosolic; therefore, for this metabolic pathway to pass, oxaloacetate or phosphoenolpyruvate must be transported from mitochondria into the cytoplasm. The specific transport mechanism depends on the organism and the substance, acts as a precursor in glucose synthesis.

If the precursor is pyruvate, the malate transport route is used predominantly. Pyruvic acid is transferred to the mitochondrial matrix or is formed there from the amino acid alanine in the transamination reaction, here the carboxylase reaction takes place. The formed oxaloacetate cannot be transported to the cytzole, due to the fact that the inner mitochondrial membrane does not have a transporter. Therefore, oxaloacetate is reduced by malate dehydrogenase to malate due to the transfer of a hydride ion with NAD H. Despite the fact that the standard change in free energy for this reaction is quite high, under conditions typical for the mitochondrial matrix (in particular, a high concentration of oxaloacetate), it is reversible (ΔG ~ 0). The formed L-malate leaves the mitochondria mediated by a special carrier and is oxidized again to oxaloacetate in the cytoplasm. The latter turns into a FEP. This path ensures the export to the cytosol not only of oxaloacetate, but also of reducing equivalents of NADH, which are necessary for gluconeogenesis (reduction of 1,3-bisphosphogycerate to glyceraldehyde-3-phosphate). In the cytoplasm, the NADH / NAD + ratio is about 8 10 -4 and is a hundred thousand times less than in mitochondria. The formation of malate in the mitochondrial matrix, its transport into the cytoplasm and dehydrogenation provide a balance between the generated and used NADH in the cytoplasm during gluconeogenesis.

The onset of gluconeogenesis is somewhat different when lactate serves as a substrate for glucose synthesis (formed in erythrocytes or skeletal muscles during intense exertion). In this case, lactic acid is dehydrogenated in the cytoplasm, this reaction is a source of NADH, which means that there is no need to transfer reducing equivalents in the form of malate from mitochondria. The formed pyruvate is transported to the mitochondria, where it is a substrate for pyruvate carboxylase. After that, oxaloacetate immediately in the matrix is \u200b\u200bsubject to decarboxylation and phosphorylation due to mitochondrial phosphoenolpyruvate carboxykinase. Formed phosphoenolpyruvate leaves the mitochondria.

There is another way that does not provide for the transfer of NADH - aspartate. In this case, oxaloacetate in the matrix enters into a transamination reaction with amino acids, catalyzed by ASAT. As a result, it is converted to aspartate, which is transported to the cytosol. There again, transamination occurs with the participation of aspartate aminotransferase, resulting in the formation of oxaloacetate. This pathway is also used when lactic acid is the precursor in gluconeogenesis, in particular, organisms that do not contain mitochondrial PMT-kabroxykinase.

2.2. Phosphorylase reactions of gluconeogenesis

Two other irreversible stages of glycolysis are kinase reactions: phosphorylation of fructose-6-phosphate and glucose using ATP. Reverse reactions would require the transfer of the phosphate group from phosphorylated monosaccharides back to ADP, but this does not occur in gluconeogenesis, corresponding transformations instead of catalyzed by other enzymes - phosphatase (fructose-1, 6-bisphosphatase (PBP-1) and glucose-6-phosphatase). Phosphatase reactions are simple hydrolysis, the product of which is phosphate acid:

Fructose-1, 6-bisphosphate + H 2 O → fructose-6-phosphate + F n; Glucose-6-phosphate + H 2 O → glucose + F n.

Both enzymes are magnesium dependent. Glucose-6-phosphatase is absent in most tissues, therefore, gluconeogenesis in them ends with the formation of glucose-6-phosphate, which can be used for glycogen synthesis or participation in other metabolic pathways. Such tissues are unable to replenish blood glucose levels because glucose-6-phosphate cannot be transported by the plasma membrane. Glucose-6-phosphatase is present in hepatocytes and, to a lesser extent, in the cells of the liver and epithelium of the small intestine. It is localized in the cavity of the endoplasmic reticulum, where glucose-6-phosphate is transported by a special carrier, and later glucose and phosphate are downloaded by another transport protein.

3. Energy costs of gluconeogense

The formation of glucose from pyruvate is a thermodynamically unfavorable process; therefore, it must be associated with extragonic reactions, namely, the hydrolysis of nucleotide triphosphates. The total equation of gluconeogenesis, in the case when pyruvate acts as the initial substance, looks like this:

2 Pyruvate + 4ATP + 2GTP + 2NADH (H +) + 4H 2 O → glucose + 4ADP + 2GTP + 6F n + 2NAD +;

So for the formation of one glucose molecule, the energy of six high-energy phosphate groups is required (four from ATP and two from GTP). This process also uses two NADH molecules to reduce 1,3-bisphosphoglycerate.

For comparison, the total equation of glycolysis:

Glucose + 2ADP + 2P p + NAD + → 2 pyruvate + 2ATP + 2H 2 O + NADH (H +);

It is obvious that gluconeogenesis is not simply the reverse of glycolysis, since in this case only two ATP molecules would be enough for its passage. Gluconeogenesis is a relatively energetically "expensive" metabolic pathway, much of the energy is required to ensure its irreversibility. According to cellular conditions, the total change in free energy during glycolysis is about -63 kJ / mol, and in gluconeogenesis - 16 kJ / mol.

4. Precursors in glucose synthesis

Glucogenny amino acids
Alanin	Pyruvate
Cysteine
Glycine
Serine
Threonine
Tryptophan
Arginine	α-ketoglutarate
Glutamate
Glutamine
Histidine
Proline
Isoleucine	Succinyl-CoA
Methionine
Threonine
Valine
Phenylalanine	Fumarate
Tyrosine
Asparagine	Oxaloacetate
Aspartate

4.1. Pyruvate and TCA Intermediates

The described metabolic pathway of gluconeogenesis can be used for the biosynthesis of glucose not only from pyruvate and lactate, but also many other substances, in particular, intermediate products of the tricarboxylic acid cycle (TCA). Compounds such as citrate, isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate and malate are converted in the course of TCA to oxaloacetate, and therefore can be substrates for gluconeogenesis.

Among the glucogenic amino acids, alanine and glutamine are of greatest importance for gluconeogenesis, since they are the main carriers of amino groups from various organs to the liver. In the mitochondria of hepatocytes, amino groups are cleaved from them, and carbon skeletons are used for the biosynthesis of glucose.

4.2. Glycerol

The hydrolysis product of neutral fats, gilcerol, can also act as a precursor in the synthesis of glucose. For this, in liver cells, it is phosphorylated by glycerol kinase, after which the second carbon atom is oxidized and glyceraldehyde-3-phosphate is formed, which can enter into gluconeogenesis. Although glycerol phosphate is an important precursor in the synthesis of triglycerides in adipocytes, these cells lack glycerol kinase. Therefore, they use an abbreviated version of gluconeogenesis for the synthesis of this substance: hilceoneogenesis, which includes the conversion of pyruvate to dihydroxyacetone phosphate, followed by its reduction to glycerol phosphate.

4.3. Fatty acid

5. Regulation of gluconeogenesis

If glycolysis and gluconeogenesis could occur simultaneously with high intensity in the cell, the result would be the useless consumption of energy and converting it into heat. For example phosphofructokinase and fructose-1, 6-phosphatase reactions:

Fructose-6-phosphate + ATP → fructose-1, 6-bisphosphate + ADP; Fructose-1, 6-bisphosphate + H 2 O → fructose-6-phosphate + F n;

would give in total only ATP hydrolysis (the so-called substrate cycle occurs)

ATP + H 2 O → ADP + F n.

Therefore, these two pathways are reciprocally regulated alosterically, by covalent modification of enzymes and regulation of their synthesis. The rate of gluconeogenesis is also influenced by the availability of substrates. In general, when a cell needs energy, glycolysis occurs more actively in it, and when energy is in excess, gluconeogenesis prevails.

5.1. Regulation of pyruvate carboxylase

Piurvate carboxylase is the first regulatory enzyme of gluconeogenesis. To function, it requires the addition of an alosteric activator acetyl-CoA, a high level of which indicates a sufficient supply of fatty acids, which can be oxidized in order to obtain energy. However, the product of the pyruvate carboxylase reaction - oxaloacetate - is used to replenish the tricarboxylic acid cycle, and not for gluconeogenesis, unless the TCA is inhibited by high levels of ATP or NADH. ADP is a negative modulator of pyruvate carboxylase.

5.2. Regulation of PMT-carboxykinase

PMT-carboxykinase catalyzes the first comitational step of gluconeogenesis (that is, it uniquely determines the metabolism of a certain compound along this pathway). In mammals, its regulation occurs mainly at the transcriptional level in response to changes in diet and hormone levels. In particular, glucagon, a gene for PMT-carboxykinase, activating the expression of the latter.

5.3. Regulation of fructose-1, 6-bisphosphatase

The last regulatory enzyme of gluconeogenesis is inhibited by AMP, a high level of which indicates the depletion of ATP reserves. In hepatocytes, its activity is tied to the level of glucose in the blood due to the signaling molecule fructose-2, 6-bisphosphate, which simultaneously acts as an alosteric inhibitor of fructose-1, 6-bisphosphatase and an alosteric activator of the corresponding enzyme of glycolysis - phosphofructokinase. The concentration of fructose-2, 6-bisphosphate depends on the rate of its formation from fructose-6-phosphate phosphofructokinase-2 (FFK-2) and hydrolysis of fructose-2, 6-bisphosphatase (FBPhase-2). FFK-2 and FBFase-2 are two different activities of one bifunctional enzyme, which is "switched" by phosphorylation.

In the case when the level of glucagon in the blood is high, it stimulates the cAMP-dependent signaling pathway in hepatocytes, which leads to the phosphorylation of the bifunctional enzyme by protein kinase A. The phosphorylated form of this protein functions as PBS-2 and hydrolyzes fructose-2, 6-bisphosphate, as a result which is the activation of fructose-1, 6-bisphosphatase and inhibition of phosphofructokinase-1. So gluconeogenesis is more intense than glycolysis. Insulin causes the opposite response: dephosphorylation of a bifunctional enzyme, an increase in the concentration of fructose-2, 6-bisphosphate, activation of FFK-1 and inhibition of FBPase-1.

Notes

Sources

• Berg JM, Tymoczko JL, Stryer L Biochemistry 6th. - WH Freeman and Company, 2007. ISBN 0-7167-8724-5.
• Nelson DL, Cox MM Lehninger Principles of Biochemistry 5th. - WH Freeman, 2008. ISBN 978-0-7167-7108-1.
• Prescott LM Microbiology 5th. - McGraw-Hill, 2002. ISBN 0-07-282905-2.
• Voet D., Voet JG Biochemistry 4th. - S. 487-496. - Wiley, 2011. ISBN 978-0470-57095-1.
• Gubsky Yu.I. Biological chemistry. - P. 191. - Kiev-Odessa: New book, 2007.

Aerobic breakdown of glucose

The energy value of aerobic breakdown of glucose.

Aerobic glycolysis produces 10 moles of ATPR per mole of glucose. So, in reactions 7, 10, 4 mol of ATP is formed by substrate phosphorylation, and in reaction 6, 6 mol of ATP (per 2 mol of glyceroaldehyde phosphate) is synthesized by oxidative phosphorylation.

Balance aerobic glycolysis.

The total effect of aerobic glycolysis is 8 mol of ATP, since reactions 1 and 3 use 2 mol of ATP. Further oxidation of two mol of pyruvate in the general pathways of catabolism is accompanied by the synthesis of 30 mol of ATP (15 mol for each molecule of pyruvate. Therefore, the total energetic effect of aerobic decomposition of glucose to end products is 38 mol of ATP.

Significance of anaerobic glycolysis

Anaerobic and aerobic glycolysis are energetically unequal. The formation of two moles of lactate from glucose is accompanied by the synthesis of only two moles of ATP, because NADH, obtained by oxidation of glyceroaldehyde phosphate, is not used by the respiratory chain, but is accepted by pyruvate.

Anaerobic breakdown of glucose.

Anaerobic glycolysis, despite its small energetic effect, is the main source of energy for skeletal muscles in the initial period of intense work, that is, in conditions when oxygen supply is limited. In addition, mature red blood cells extract energy through anaerobic oxidation of glucose because they do not have mitochondria.

Alcoholic fermentation - chemical reaction fermentation, carried out by yeast, as a result of which one glucose molecule is converted into 2 molecules of ethanol and 2 molecules of carbon dioxide.

Alcoholic fermentation (carried out by yeast and some types of bacteria), during which pyruvate is split into ethanol and carbon dioxide. From one glucose molecule, the result is two molecules of drinking alcohol (ethanol) and two molecules of carbon dioxide. This type of fermentation is very important in the production of bread, brewing, winemaking and distilling. If the starter culture has a high concentration of pectin, a small amount of methanol may also be produced. Usually only one of the products is used; in the production of bread, alcohol evaporates during baking, and in the production of alcohol, carbon dioxide is usually released into the atmosphere, although recently they are trying to utilize it.

40 gluconeogenesis - the process of formation in the liver and partly in the cortical substance of the kidneys (about 10%) of glucose molecules from molecules of other organic compounds - energy sources, for example, free amino acids, lactic acid, glycerin

.

The summary equation of gluconeogenesis: 2 CH 3 COCOOH + 4ATP + 2GTP + 2NADH. H + + 6 H 2 O \u003d C 6 H 12 O 6 + 2NAD + 4ADP + 2GDP + 6P n .

Role in the body

During fasting in the human body, nutrient reserves are actively used ( glycogen, fatty acid). They split up amino acids, keto acids and other non-carbohydrate compounds. Most of these compounds are not excreted from the body, but are reused. Substances are transported by blood to liver from other tissues, and are used in gluconeogenesis for the synthesis glucose - the main source of energy in the body. Thus, when the body's reserves are depleted, gluconeogenesis is the main supplier of energy substrates.

Most stages gluconeogenesis represents reversal of glycolysis reaction... Only 3 glycolysis reactions (hexokinase, phospho-fructokinase and pyruvate kinase) are irreversible, therefore, in the process of gluconeogenesis at 3 stages, other enzymes... Consider the synthesis path glucose from pyruvate. Formation of phosphoenolpyruvate from pyruvate. The synthesis of phosphoenolpyruvate is carried out in several stages. Initially pyruvate influenced pyruvate carboxylase and with the participation of CO 2 and ATF carboxylated to form oxaloacetate: Then oxaloacetate as a result decarboxylation and phosphorylation under the influence enzyme phosphoenolpyruvate carboxylase is converted to phosphoenolpyruvate. Donor phosphate residue in reactions serves as guanosine triphosphate (GTP): It was found that the formation of phosphoenolpyruvate involves enzymes cytosol and mitochondria... The first stage of synthesis takes place in mitochondria (Figure 10.6). Pyruvate carboxylase, which catalyzes this reaction, is an allosteric mitochondrial enzyme... As allosteric activator given enzyme requires acetyl-CoA. Membrane mitochondria impermeable to the resulting oxaloacetate. The last one is here, in mitochondria, is reduced to malate: Reaction proceeds with the participation of mitochondrial NAD-dependent malate dehydrogenase... AT mitochondriathe ratio of NADH / NAD + is relatively high, and therefore intramitochondrial oxaloacetate is easily reduced to malate, which easily leaves mitochondria through mitochondrial membrane... In the cytosol, the NADH / NAD + ratio is very small, and malate is re-oxidized with the participation of the cytoplasmic NAD-dependent malate dehydrogenase: Further conversion of oxaloacetate to phosphoenolpyruvate occurs in the cytosol cells... Conversion of fructose-1,6-bisphosphate to fructose-6-phosphate. Phospho-enolpyruvate, formed from pyruvate, as a result of a number of reversible glycolysis reactions turns into fructose-1,6-bisphosphate. This is followed by phosphofructokinase reactionwhich is irreversible. Gluconeogenesis goes around this endergonic reactions... The conversion of fructose-1,6-bis-phosphate to fructose-6-phosphate is catalyzed by a specific phosphatase: .Education glucosefrom glucose-6-phosphate. In the subsequent reversible stage biosynthesis of glucosefructose-6-phosphate is converted to glucose-6-phosphate. The latter can be dephosphorylated (i.e. reactionbypasses hexokinase reactions) influenced enzyme glucose 6-phosphatase: Regulation gluconeogenesis... An important point in the regulation of gluconeogenesis is reactioncatalyzed pyruvate carboxylase... The role of a positive allosteric modulator of this enzymeperforms acetyl-CoA. In the absence of acetyl-CoA enzyme almost completely devoid of activity... When in cageaccumulates mitochondrial acetyl-CoA, biosynthesis of glucose from pyruvate is enhanced. It is known that acetyl-CoA is simultaneously a negative modulator of the pyruvate dehydrogenase complex (see below). Consequently, the accumulation of acetyl-CoA slows down the oxidative decarboxylation pyruvate, which also contributes to the conversion of the latter into glucose... Another important point in regulation gluconeogenesis – reactioncatalyzed by fructose-1,6-bisphosphatase - enzymewhich is inhibited AMF... Opposite action AMF has on phosphofructokinase, i.e. for this enzyme he is allosteric activator... At low concentration of AMP and high level ATF stimulation occurs gluconeogenesis... On the contrary, when the value of the ratio ATF/AMF small, in cage splitting is observed glucose... Shown, that gluconeogenesis can also be regulated indirectly, i.e. through change enzyme activitynot directly involved in the synthesis glucose... So, it was found that glycolysis enzymepyruvatkinase exists in 2 forms - L and M. Form L (from English liver - liver) prevails in tissuescapable of gluconeogenesis... This form is inhibited by excess ATF and some amino acids, in particular ala-nin. The M-form (from the English muscle - muscles) is not subject to such regulation. In conditions of sufficient security cells energy is inhibition of the L-form pyruvate kinase... As a consequence of inhibition, it slows down glycolysis and conditions are created that favor gluconeogenesis. Finally, it is interesting to note that between glycolysisflowing intensively in muscle tissue with her vigorous activity, and gluco-neogenesis, especially characteristic of hepatic fabrics, there is a close relationship. At maximum activity muscles as a result of strengthening glycolysis excess is formed lactic aciddiffusing into blood, at liver a significant part of it turns into glucose(gluconeogenesis). Such glucose can then be used as an energy substraterequired for activity muscle tissue.

41. Glycogen - the main form of glucose deposition in animal cells. In plants, starch performs the same function. Structurally, glycogen, like starch, is a branched polymer of glucose.

However, glycogen is more branched and more compact. Branching allows for the rapid release of a large number of terminal monomers during the breakdown of glycogen. The synthesis and breakdown of glycogen are not reversed, these processes occur in different ways.

Biosynthesis of *** glycogen

Glycogen is synthesized during digestion (within 1-2 hours after ingestion of carbohydrate food). Glycogenesis is especially intense in the liver and skeletal muscles. In the initial reactions, UDF-glucose is formed (reaction 3), which is an activated form of glucose that is directly involved in the polymerization reaction (reaction 4). This last reaction is catalyzed by glycogen synthase, which attaches glucose to the oligosaccharide or to the glycogen molecule already present in the cell, increasing the chain with new monomers. For preparation and incorporation into the growing polysaccharide chain, an energy of 1 mole of ATP and 1 mole of UTP is required. Branching of the polysaccharide chain occurs with the participation of the enzyme amylo -1,4-1,6-glycosyl transferase by breaking one -1,4-bond and transferring the oligosaccharide residue from the end of the growing chain to its middle with the formation of -1 in this place, 6-glycosidic linkage. The glycogen molecule contains up to 1 million glucose residues, therefore, a significant amount of energy is spent on synthesis. The need to convert glucose into glycogen is due to the fact that the accumulation of a significant amount of glucose in the cell would lead to an increase in osmotic pressure, since glucose is a highly soluble substance. On the contrary, glycogen is contained in the cell in the form of granules, and is slightly soluble. The breakdown of glycogen - glycogenolysis - occurs between meals.

The second option for ticket 40.

Glucose biosynthesis - gluconeogenesis

Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors. In mammals, this function is performed mainly by the liver, to a lesser extent by the kidneys and cells of the intestinal mucosa. The body has enough glycogen stores to meet the glucose needs between meals. With carbohydrate or complete starvation, as well as under conditions of prolonged physical work, the concentration of glucose in the blood is maintained due to gluconeogenesis. This process can involve substances that are capable of converting into pyruvate or any other metabolite of gluconeogenesis.

Moreover, the use of primary substrates in gluconeogenesis occurs in various physiological states. Thus, under starvation conditions, part of tissue proteins breaks down into amino acids, which are then used in gluconeogenesis. During the breakdown of fats, glycerin is formed, which is involved in gluconeogenesis through dioxyacetone phosphate. Lactate, formed during intense physical work in the muscles, is then converted into glucose in the liver. Therefore, the physiological role of gluconeogenesis from lactate and from amino acids and glycerol is different. The synthesis of glucose from pyruvate proceeds as in glycolysis, but in the opposite direction.

Gluconeogenesis.

Enzymes: 1-pyruvate carboxylase, 2-phosphoenolpyruvate carboxykinase, 3-phosphatase fru-1,6-diphosphate, 4-glucose-6-phosphatase.

Seven glycolysis reactions are readily reversible and are used in gluconeogenesis. But the three kinase reactions are irreversible and must be shunted. Thus, fructose-1,6-diphosphate and glucose-6-phosphate are dephosphorylated by specific phosphatases, and pyruvate is phosphorylated to phosphoenolpyruvate through two intermediate steps via oxaloacetate. The formation of oxaloacetate is catalyzed by pyruvate carboxylase. This enzyme contains biotin as a coenzyme. Oxaloacetate is formed in mitochondria, transported to the cytosol, and involved in gluconeogenesis. It should be noted that each of the irreversible reactions of glycolysis, together with the corresponding irreversible reaction of gluconeogenesis, constitute a cycle called the substrate cycle.

Gluconeogenesis, irreversible reactions.

There are three such cycles - corresponding to three irreversible reactions. The result of the simultaneous occurrence of the reactions of the substrate cycles will be energy consumption. Substrate cycles can proceed under conditions of normal metabolism in the liver and have a definite biological significance. In addition, these cycles serve as points of application of regulatory mechanisms, as a result of which the flow of metabolites changes either along the path of glucose breakdown or along the path of its synthesis. The summary equation of gluconeogenesis from pyruvate:

2 pyruvate + 4 ATP + 2 GTP + 2 (NADH) + 4 H 2 O Glucose + 4 ADP + 2 GDP + 2 NAD + + 6 H 3 PO 4.

Up to 80 g of glucose can be synthesized in the human body per day. The synthesis of 1 mol of glucose from pyruvate consumes 6 high-energy bonds (4 ATP and 2 GTP).

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