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Metabolism of carbohydrates in muscles. Carbohydrate metabolism and features of energy supply to the brain

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Biology and genetics

At rest, significant amounts of glucose are stored in the form of glycogen. Metabolism of carbohydrates in muscles ensures the creation of tissue reserves of glycogen at rest and the use of these reserves, as well as incoming glucose, during strenuous work; the basic energy needs of all types of muscles are satisfied mainly through the oxidation of fat metabolic products. Phosphorylation of glucose in muscles occurs under the action of hexokinase in the liver; this process is catalyzed by glucokinase. If in the blood flowing to the brain...

Ticket 32.

Metabolism of carbohydrates in muscles.

The liver takes into account the requests of other organs and tissues regarding carbohydrate metabolism. In muscles, carbohydrate metabolism occurs in accordance with the principle of self-service.

The goal of the muscle cell is to most effectively use incoming glucose to produce ATP, which is necessary for the mechanical work of contraction. At rest, significant amounts of glucose are stored in the form of glycogen. The cytoplasm of muscle cells contains high concentrations of glycolytic enzymes, and the abundance of mitochondria ensures the efficient breakdown of glycolytic products through the citric acid pathway and the electron transport chain. Only under conditions of extreme fatigue do these aerobic processes cope with the accumulation of lactate.

Glycogenesis occurs in the muscles; the muscle performs only a few synthetic functions. Key enzymes of gluconeogenesis are absent in muscles, andgluconeogenesis does not occur. For restorative synthesis of NADP in muscle. N is not required, and phosphoglucone This pathway is almost non-functional.

Carbohydrate metabolism in muscles ensures the creation of tissue glycogen reserves at rest and the use of these reserves, as well as incoming glucose during strenuous work; the basic energy needs of all types of muscles are satisfied mainly through the oxidation of fat metabolic products. Neither slow-twitch smooth muscle tissue nor cardiac muscle consumes glucose significantly. During hard work, the heart provides itself with lactate for oxidation.

Carbohydrate metabolism in muscle.

Phosphorylation of glucose in muscles occurs under the action of hexokinase, in the liver this process is catalyzed by glucokinase. These enzymes differ in K m. K m hexokinase is significantly lower than K m glucokinase. The muscle enzyme hexokinase is involved in intracellular regulation, i.e. this enzyme will phosphorylate glucose only as long as glucose-6-p is used in the muscles for glycolysis or glycogen formation.

Another major difference between liver and muscle tissue is the absence of the enzyme glucose-6-phosphatase in muscle.

Carbohydrate metabolism in the brain.

Compared to all organs of the body, brain function is most dependent on carbohydrate metabolism. If the glucose concentration in the blood flowing to the brain becomes half normal, then loss of consciousness occurs within a few seconds, and death occurs within a few minutes. In order to ensure the release of sufficient energy, glucose catabolism must be carried out in accordance with aerobic mechanisms; This is evidenced by the even higher sensitivity of the brain to hypoxia than to hypoglycemia. Glucose metabolism in the brain ensures the synthesis of neurotransmitters, amino acids, lipids, and nucleic acid components.The phosphogluconate pathway functionsto a small extent, providing NADP. H for some of these syntheses. The main catabolism of glucose in brain tissue occurs through the glycolytic pathway.

Brain hexokinase has a high affinity for glucose, which ensures efficient use of glucose by the brain. The activity of glycolytic enzymes is high.

The high activity of mitochondrial enzymes of the citric acid cycle prevents the accumulation of lactate in brain tissue; Most of the pyruvate is oxidized to Ac-CoA. A small portion of Ac-CoA is used to form the neurotransmitter acetylcholine. The main amount of Ac-CoA undergoes oxidation in the citric acid cycle and provides energy. Krebs cycle metabolism is used to synthesize aspartate and glutamate. These amino acids ensure the neutralization of ammonia in brain tissue.

The brain contains little glycogen (0.1% of total weight); this reserve is used up very quickly.

Metabolism of carbohydrates in brain tissue.

During prolonged fasting, the brain uses ketone bodies as an energy source. In extreme cases, amino acids such as glutamate and aspartate are converted into the corresponding keto acids, which are capable of oxidation to produce energy.

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Carbohydrates are a large group of organic compounds found in all living organisms. Carbohydrates are considered the body's main source of energy. In addition, they are necessary for the normal functioning of the nervous system, mainly the brain. It has been proven that during intense mental activity, carbohydrate consumption increases. Carbohydrates also play an important role in protein metabolism and fat oxidation, but their excess in the body creates fat deposits.

Carbohydrates come from food in the form of monosaccharides (fructose, galactose), disaccharides (sucrose, lactose) and polysaccharides (starch, fiber, glycogen, pectin), turning into glucose as a result of biochemical reactions. The body's need for carbohydrates is approximately 1 g per kilogram of body weight. Excessive consumption of carbohydrates, especially sugar, is extremely harmful.

The main sources of carbohydrates from food are: bread, potatoes, pasta, cereals, and sweets. Sugar is a pure carbohydrate. Honey, depending on its origin, contains 70-80% glucose and fructose. In addition, consumption of carbohydrates in the form of refined sugar and sweets contributes to the development of dental caries. Therefore, it is recommended to use more foods containing polysaccharides (porridge, potatoes), fruits and berries as sources of carbohydrates.

The average daily human need for carbohydrates is 4-5 g per kilogram of body weight. It is recommended to introduce 35% of carbohydrates in the form of granulated sugar, honey, jam, and the rest should preferably be replenished with bread, potatoes, cereals, apples

Nervous regulation

Excitation of sympathetic nerve fibers leads to the release of adrenaline from the adrenal glands, which stimulates the breakdown of glycogen through the process of glycogenolysis. Therefore, when the sympathetic nervous system is irritated, a hyperglycemic effect is observed. On the contrary, irritation of parasympathetic nerve fibers is accompanied by increased secretion of insulin by the pancreas, the entry of glucose into the cell and a hypoglycemic effect.

Hormonal regulation

Insulin, catecholamines, glucagon, somatotropic and steroid hormones have different, but very pronounced effects on various processes of carbohydrate metabolism. For example, insulin promotes the accumulation of glycogen in the liver and muscles, activating the enzyme glycogen synthetase, and suppresses glycogenolysis and gluconeogenesis.

The insulin antagonist glucagon stimulates glycogenolysis. Adrenaline, stimulating the action of adenylate cyclase, affects the entire cascade of phosphorolysis reactions. Gonadotropic hormones activate glycogenolysis in the placenta. Glucocorticoid hormones stimulate the process of gluconeogenesis. Growth hormone affects the activity of enzymes of the pentose phosphate pathway and reduces the utilization of glucose by peripheral tissues.

Carbohydrate metabolism is assessed by the content of sugar (glucose), lactic acid (lactate) and other acids in the blood.

Lactic acid Normally it is 0.33-0.78 mmol/l. After training (competition), lactate increases to 20 mmol/l or even more. Lactic acid is the end product of glycolysis; its level in the blood allows us to judge the relationship between the processes of aerobic oxidation and anaerobic glycolysis. Hypoxia during physical activity leads to an increase in the content of lactic acid in the blood; the resulting lactate has an adverse effect on contractile processes in the muscles. In addition, a decrease in intracellular pH can reduce enzymatic activity and thereby inhibit physico-chemical mechanisms of muscle contraction, which ultimately negatively affects athletic performance.

Blood glucose concentration normal - 4.4-6.6 mmol/l. With prolonged physical activity, the presence of sugar in the blood decreases, especially in weakly trained athletes during participation in competitions held in hot and humid climates.

The level of glucose and lactic acid in the blood can be used to judge the ratio of aerobic and anaerobic processes in working muscles.

Creatine before training is 2.6-3.3 mg%, and after training it increases to 6.4 mg%. As training increases, the creatine content in the blood after exercise decreases. An athlete’s body, adapted to physical activity, reacts by increasing the level of creatine in the blood to a lesser extent than a poorly trained one. Prolonged persistence of elevated levels of creatine in the blood indicates incomplete recovery.

A child’s need for carbohydrates is significant: an infant should receive 10-15 g per 1 kg of body weight, approximately the same amount of carbohydrates is required for children under the age of one year and older, and in children school age the amount of carbohydrates in the diet can increase to 15 g/kg body weight.

When determining the optimal amount of carbohydrates in the diet, calorie content and a certain ratio of other food components, fats, proteins and carbohydrates must be taken into account. The most physiological ratio should be considered B:F:U: 1:1:4 (that is, 100 g protein: 100 g fat: 400 g carbohydrates)

In the first months of life, the main carbohydrate in food is the disaccharide lactose (milk sugar). The lactose content in human milk averages 70 g/l, and in cow's milk - 48 g/l. Lactose in the gastrointestinal tract is hydrolyzed into glucose and galactose by the enzyme lactase. The intensity of enzymatic hydrolysis of lactose in the intestines of children of different ages is not the same: it is somewhat reduced in newborns and maximum in infancy.

Monosaccharides are absorbed, enter the blood and are carried to different organs and tissues, entering the path of intracellular metabolism. Most of the galactose in the liver is converted into glucose, partly it is used for the synthesis of gangliosides and cerebrosides. Glucose from the liver and muscles is deposited in the form of glycogen.

As the child grows, lactose in the diet gives way to sucrose, starch, glycogen, and in schoolchildren 7-9 years old, half of all carbohydrates are polysaccharides; lactose metabolism decreases. New enzyme systems are included in the digestion process. However, enzymes that provide cavity digestion in older children early age inactive and even completely absent. Young children are characterized by membrane digestion.

Nerve tissue, which makes up only 2% of the human body weight, consumes 20% of the oxygen entering the body. 100-120 g of glucose are oxidized in the brain per day. In a state of quiet wakefulness, the brain accounts for approximately 15% of total metabolism; therefore, at rest, brain metabolism per unit tissue mass is approximately 7.5 times higher than the average metabolism of tissues not related to the nervous system. Most of the increased brain metabolism is associated with neurons, not glial tissue.

The main consumer of energy in neurons is the ion pumps of their membranes, transporting mainly sodium and calcium ions outward, and potassium ions into the cell. During an action potential, the need for additional membrane transport increases to restore the appropriate difference in ion concentrations on both sides of the neuronal membranes. The function of a nerve cell is to conduct a nerve impulse, which depends on the concentration gradient of K+ and Na+ ions inside and outside the cell. ATP is needed to maintain active work Na+/K+ - ATPase - an enzyme that maintains the resting potential and restores it after the passage of a nerve impulse.

Therefore, during intense brain activity, the metabolism of nervous tissue can increase by 100-150%. The main way to obtain energy is the aerobic breakdown of glucose along the GBP pathway. Glucose is almost the only energy substrate entering the nervous tissue, which can be used by its cells to form ATP. Complete oxidation of 1 gram molecule of glucose is accompanied by the release of 686,000 calories of energy, while only 12,000 calories are needed to form 1 gram molecule of ATP. Due to the sequential step-by-step breakdown of a glucose molecule during the oxidation of each mole, 38 moles of ATP are formed. The penetration of glucose into brain tissue does not depend on the action of insulin, which does not penetrate the blood-brain barrier. The effect of insulin is manifested only in peripheral nerves. Consequently, in patients with severe diabetes, with a practically zero level of insulin secretion, glucose easily diffuses into neurons, which is extremely important for preventing the loss of mental functions in this category of patients.

Under normal conditions, almost all the energy used by brain cells is provided by glucose delivered by the blood. Glucose must be constantly supplied from capillary blood: at any moment, a two-minute supply of glucose in neurons in the form of glycogen is required. Oxidation of non-carbohydrate substrates to produce energy is impossible, therefore, during hypoglycemia and/or even short-term hypoxia, little ATP is formed in the nervous tissue. The consequence of this is the rapid onset of a coma and irreversible changes in brain tissue. The processes of glucose metabolism are carried out in the body of the neuron and its processes, Schwann cells (myelin sheath), therefore, all parts of the nervous tissue are capable of synthesizing ATP.

Glucose immediately binds to phosphate and in this form can no longer leave the cell. The activity of isocitrate dehydrogenase, even with a normal level of glucose utilization at rest, is maximum. Therefore, with increased energy consumption, there is no possibility of accelerating TTC reactions. The formation of NADPH2, which is used in nervous tissue mainly for the synthesis of fatty acids and steroids, is ensured by the relatively high rate of the GMP pathway of glucose breakdown. ATP energy is used unevenly in nervous tissue. Similar to skeletal muscles, the functioning of nervous tissue is accompanied by sharp changes in energy consumption. An abrupt increase in energy expenditure occurs during a very rapid transition from sleep to wakefulness.

There is another mechanism for this: the formation of creatine phosphate. Despite the exceptional importance of ATP as a method of energy transformation, this substance is not the most representative store of high-energy phosphate bonds in cells. The amount of creatine phosphate containing high-energy phosphate bonds in cells is 3-8 times greater. In addition, under body conditions, the high-energy phosphate bonds of creatine phosphate contain more than 13,000 k/mol.

Unlike ATP, creatine phosphate cannot act as an agent directly coupled to energy transfer nutrients functional systems of the cell, but it can exchange energy with ATP. When extremely large amounts of ATP are present in cells, the energy from ATP is used to synthesize creatine phosphate, which becomes an additional energy store. Then, as ATP is used, the energy contained in phosphocreatine is quickly returned to ATP, which the latter can transfer to the functional systems of cells. This reaction is completely reversible, its direction depends on the ATP/ADP ratio in the cells of the nervous tissue. Under resting conditions, the concentration of ADP in cells is low, so chemical reactions that depend on ADP as one of the substrates occur slowly. Thus, ADP is the main rate-limiting factor in almost all energy metabolic pathways. When cells are activated, ATP is converted to ADP, increasing its concentration in proportion to the degree of cell activity. Increasing the concentration of ADP automatically increases the rate of all metabolic reactions aimed at releasing energy from nutrients. Reduced cell activity stops the release of energy due to the very rapid conversion of ADP to ATP.

It is known that about 20% of the energy produced by the human body is spent on brain function. But what does the brain itself spend this energy on? Until recently, it was believed that almost all the energy consumed by the brain is used to transmit nerve impulses, in other words, to mental activity. Today it is believed that only two-thirds of the energy consumed by the brain is spent on the propagation of impulses, and the remaining part goes to maintaining the vital activity of the cells of the brain itself (S.E. Severin, 2009). Experiments conducted on laboratory rats using magnetic resonance imaging helped establish the relationship between metabolic rate - the "rate" of ATP molecule synthesis - and energy consumption at different levels of brain activity. This, in turn, made it possible to estimate what part of the total energy expenditure does not depend on brain activity and is spent on “own needs,” in this case, on maintaining the so-called isoelectric state: the equality of positive and negative charges in the cells of the brain tissue.

It is known that physical exercise leads to significant consumption of glucose by muscles. For this reason, during physical activity, the level of glucose in a person’s blood decreases. In this case, the brain switches to using lactic acid. One of the most important factors that determines the specific response of different neurons to a lack of oxygen is their difference in energy needs. The latter, apparently, is determined by the degree of dendritic branching and the total area of the cell membrane, the polarization of which requires constant energy consumption. Systems and centers that include predominantly neurons rich in dendrites (the neocortex with its rich network of interneurons, Purkinje cells of the cerebellum), according to this hypothesis, are especially vulnerable to hypoxia.

Probably, the peculiarities of the biochemistry of neurons in different areas of the brain also play a significant role (the theory of pathoclysis is the tendency of a certain anatomical formation of the central nervous system to react with a certain pathological process to a given damaging factor, for example, the formation of foci of necrosis and cysts in the globus pallidus during carbon monoxide poisoning (Rubenstein, 1998) It is by the difference in the biochemical structure of neurons that they try to explain the unequal vulnerability of different sectors of the hippocampus. When dying from blood loss against the background of prolonged arterial hypotension, the characteristics of the blood supply to various formations of the brain become of utmost importance, since in these cases the areas of the brain located closer to the great vessels are in a more advantageous position (subcortical areas, systems of the base of the brain, especially the brainstem), the functions of which fade away later than the functions of the new cortex of the cerebral hemispheres.

The distribution of areas of damage in the brain that has experienced cessation of blood circulation is determined by the specifics of metabolism various types neurons, as well as the characteristics of the blood supply to different parts and areas of the brain. To these two factors of selective vulnerability of various parts of the brain, one should add the factor of the relative complexity of the function (and, accordingly, its phylogenetic “age”), since phylogenetically younger functions, which are also more complex (for example, thinking), are served by a large number of neural systems, located at many, including higher anatomical levels and, naturally, turn out to be more vulnerable when oxygen starvation. Of no small importance is the degree of functional activity of the brain systems (and, consequently, their energy needs and the state of blood supply) at the time of hypoxia.

Cerebral energy metabolism in middle age and aging Literature 1. In the cell, nutrients are oxidized under the influence of oxygen and with the participation of enzymes. Subject to the physical and chemical conditions characteristic of the body, the energy of phosphate macroergic bonds of the ATP molecule is 7300 calories per 1 mole. When energy is released, ATP is converted to adenosine diphosphate.

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BRAIN METABOLISM

1. The role of cellular organelles in energy processes of the nerve cell.

3. Lipid metabolism

10. Cerebral energy metabolism in middle age and aging

Literature

1. The role of cellular organelles in energy processes, nerve cell.

The main source of energy for the cell is nutrients: carbohydrates, fats and proteins. Before reaching the body cells, carbohydrates are converted into glucose, proteins are broken down into amino acids, lipids into fatty acids due to the activity gastrointestinal tract and liver. In the cell, nutrients are oxidized under the influence of oxygen and with the participation of enzymes. Almost all oxidative reactions occur in mitochondria, and the released energy is stored in the form of the high-energy compound ATP. Subsequently, it is ATP, and not nutrients, that is used to provide intracellular metabolic processes with energy.

ATP synthesis is 95% carried out in mitochondria. Pyruvic acid, fatty acids and amino acids in the mitochondrial matrix are eventually converted into acetyl-CoA, which in turn undergoes a series of enzymatic reactions under common name"tricarboxylic acid cycle" to give away its energy.

In addition, hydrogen oxidation occurs in mitochondria. During these reactions, each hydrogen atom is converted into a hydrogen ion and an electron; the electrons eventually bond with dissolved atomic oxygen to form water molecules and hydroxyl ions. Subsequently, hydrogen ions and the resulting hydroxyl ions combine to form water. These reactions release enormous amounts of energy in the form of ATP. This mechanism of ATP formation is called oxidative phosphorelation. The process occurs in mitochondria through a highly specialized mechanism called chemoosmotic.

The ATP molecule contains the nitrogenous base adenine, the pentose carbohydrate ribose and three phosphoric acid residues. Subject to the physical and chemical conditions characteristic of the body, the energy of phosphate macroergic bonds of the ATP molecule is 7300 calories per 1 mole. These connections are easily destroyed, providing intracellular processes with energy as soon as the need arises. When energy is released, ATP is converted to adenosine diphosphate. Then ATP reserves are replenished by recombining ADP with the phosphoric acid residue at the expense of nutrient energy. ATP turnover time is several minutes (Guyton A. and D. Hall, 2008)

ATP energy is used by the nerve cell to perform three essential functions:

transport of substances through numerous cell membranes (ions of potassium, calcium, magnesium, phosphorus, chlorine, organic substances);
synthesis of substances in different parts of the cell, especially during the growth phase;
conduction of a nerve impulse.

2 Carbohydrate metabolism and features of energy supply to the brain.

Nerve tissue, which makes up only 2% of the human body weight, consumes 20% of the oxygen entering the body. 100-120 g of glucose are oxidized in the brain per day.

In a state of quiet wakefulness, the brain accounts for approximately 15% of total metabolism; therefore, at rest, brain metabolism per unit tissue mass is approximately 7.5 times higher than the average metabolism of tissues not related to the nervous system. Most of the increased brain metabolism is associated with neurons, not glial tissue. The main consumer of energy in neurons is the ion pumps of their membranes, transporting mainly sodium and calcium ions outward, and potassium ions into the cell. During an action potential, the need for additional membrane transport increases to restore the appropriate difference in ion concentrations on both sides of the neuronal membranes. The function of a nerve cell is to conduct a nerve impulse, which depends on the concentration gradient of K ions+ and Na + inside and outside the cell. ATP is necessary to maintain the active functioning of Na+ /K + ATPase an enzyme that maintains the resting potential and restores it after the passage of a nerve impulse. Therefore, during intense brain activity, the metabolism of nervous tissue can increase by 100-150%.

The main way to obtain energy is the aerobic breakdown of glucose along the GBP pathway. Glucose is almost the only energy substrate entering the nervous tissue, which can be used by its cells to form ATP. Complete oxidation of 1 gram molecule of glucose is accompanied by the release of 686,000 calories of energy, while only 12,000 calories are needed to form 1 gram molecule of ATP. Due to the sequential step-by-step breakdown of a glucose molecule during the oxidation of each mole, 38 moles of ATP are formed.

The penetration of glucose into brain tissue does not depend on the action of insulin, which does not penetrate the blood-brain barrier. The effect of insulin is manifested only in peripheral nerves. Consequently, in patients with severe diabetes, with a practically zero level of insulin secretion, glucose easily diffuses into neurons, which is extremely important for preventing the loss of mental functions in this category of patients.

The processes of glucose metabolism are carried out in the body of the neuron and its processes, Schwann cells (myelin sheath), therefore, all parts of the nervous tissue are capable of synthesizing ATP.

The high rate of glucose consumption by nerve cells is ensured, first of all, by the work of highly active brain hexokinase. Unlike other tissues, here hexokinase is not a key enzyme in all glucose metabolic pathways. Brain hexokinase is 20 times more active than the corresponding liver and muscle isoenzyme. Under the influence of hexokinase and with the participation of ATP, glucose is converted into glucose-6-phosphate. Glucose phosphorylation is an irreversible process and serves as a way for glucose to be taken up by cells. Glucose immediately binds to phosphate and in this form can no longer leave the cell. The activity of isocitrate dehydrogenase, even with a normal level of glucose utilization at rest, is maximum. Therefore, with increased energy consumption, there is no possibility of accelerating TTC reactions.

Formation of NADPH 2 , which is used in nervous tissue mainly for the synthesis of fatty acids and steroids, is ensured by the relatively high rate of the GMP pathway of glucose breakdown.

ATP energy is used unevenly in nervous tissue. Similar to skeletal muscles, the functioning of nervous tissue is accompanied by sharp changes in energy consumption. An abrupt increase in energy expenditure occurs during a very rapid transition from sleep to wakefulness. There is another mechanism for this:formation of creatine phosphate. Despite the critical importance of ATP as a means of energy transformation, this substance is not the most representative store of high-energy phosphate bonds in cells

The amount of creatine phosphate containing high-energy phosphate bonds in cells is 3-8 times greater. In addition, under body conditions, the high-energy phosphate bonds of creatine phosphate contain more than 13,000 k/mol. Unlike ATP, creatine phosphate cannot act as an agent directly coupled to the transfer of nutrient energy to the functional systems of the cell, but it can exchange energy with ATP. When extremely large amounts of ATP are present in cells, the energy from ATP is used to synthesize creatine phosphate, which becomes an additional energy store. Then, as ATP is used, the energy contained in phosphocreatine is quickly returned to ATP, which the latter can transfer to the functional systems of cells.

This reaction is completely reversible, its direction depends on the ATP/ADP ratio in the cells of the nervous tissue.

Under resting conditions, the concentration of ADP in cells is low, so chemical reactions that depend on ADP as one of the substrates occur slowly. Thus, ADP is the main rate-limiting factor in almost all energy metabolic pathways. When cells are activated, ATP is converted to ADP, increasing its concentration in proportion to the degree of cell activity. Increasing the concentration of ADP automatically increases the rate of all metabolic reactions aimed at releasing energy from nutrients. Reduced cell activity stops the release of energy due to the very rapid conversion of ADP to ATP.

It is known that about 20% of the energy produced by the human body is spent on brain function. But what does the brain itself spend this energy on?

Until recently, it was believed that almost all the energy consumed by the brain is used to transmit nerve impulses, in other words, for mental activity. Today it is believed that only two-thirds of the energy consumed by the brain is spent on the propagation of impulses, and the remaining part goes to maintaining the vital activity of the cells of the brain itself (S.E. Severin, 2009).

Experiments conducted on laboratory rats using magnetic resonance imaging helped establish the relationship between metabolic rate “rate” of ATP molecule synthesis and energy consumption at different levels of brain activity.

This, in turn, made it possible to estimate what part of the total energy expenditure does not depend on brain activity and is spent on “own needs,” in this case, on maintaining the so-called isoelectric state: the equality of positive and negative charges in the cells of the brain tissue.

One of the most important factors that determines the specific response of different neurons to a lack of oxygen is their difference in energy needs. The latter, apparently, is determined by the degree of dendritic branching and the total area of the cell membrane, the polarization of which requires constant energy consumption. Systems and centers that primarily include neurons rich in deidrites (the neocortex with its rich network of interneurons, Purkinje cells of the cerebellum), according to this hypothesis, are especially vulnerable to hypoxia. Probably, the peculiarities of the biochemistry of neurons in different areas of the brain also play a significant role (the theory of pathoclysis is the tendency of a certain anatomical formation of the central nervous system to react with a certain pathological process to a given damaging factor, for example, the formation of foci of necrosis and cysts in the globus pallidus during carbon monoxide poisoning (Rubenstein, 1998) It is by the difference in the biochemical structure of neurons that they try to explain the unequal vulnerability of different sectors of the hippocampus.

When dying from blood loss against the background of prolonged arterial hypotension, the characteristics of the blood supply to various formations of the brain become of utmost importance, since in these cases, areas of the brain located closer to the main vessels (subcortical areas, systems of the base of the brain, especially the brain stem), whose functions fade away later than the functions of the neocortex of the cerebral hemispheres. The distribution of areas of damage in the brain that has experienced cessation of blood circulation is determined both by the specific metabolism of different types of neurons and by the characteristics of the blood supply to different parts and areas of the brain.

To these two factors of selective vulnerability of various parts of the brain, one should add the factor of the relative complexity of the function (and, accordingly, its phylogenetic “age”), since phylogenetically younger functions, which are also more complex (for example, thinking), are served by a large number of neural systems, located at many, including higher anatomical levels and, naturally, turn out to be more vulnerable during oxygen starvation. Of no small importance is the degree of functional activity of the brain systems (and, consequently, their energy needs and the state of blood supply) at the time of hypoxia.

3. Lipid metabolism

Most of the lipids in nervous tissue are found in the plasma and subcellular membranes of neurons and in the myelin sheaths. In nervous tissue, compared to other tissues of the body, the lipid content is very high. A feature of the lipid composition of nervous tissue can be considered the presence of phospholipids (PL), glycolipids (GL) and cholesterol (CS) and the absence of neutral fats. The nervous system contains a large number of sphingomyelins, which are insulators due to their electrical properties. Cholesterol esters can only be found in areas of active myelination. Cholesterol is intensively synthesized only in the developing brain, since in an adult the activity of OMG-CoA reductase, the key enzyme in cholesterol synthesis, is low. The content of free fatty acids in the brain is very low.

The important role of cholesterol and phospholipids in the formation of structural components of cells is due to the low rate of replacement of these substances, and their functional participation in ensuring memory processes in brain cells is associated precisely with this.

Some neurotransmitters, after interacting with specific receptors, change their conformation and change the conformation of the enzyme phospholipase C, which catalyzes the cleavage of the bond in phosphatidylinositol between glycerol and the phosphate residue, resulting in the formation of phosphoinositol and diacylglycerol. These substances are regulators of intracellular metabolism. Diacylglycerol activates protein kinase C, and phosphoinositol causes an increase in Ca concentration 2+ . Calcium ions affect the activity of intracellular enzymes and participate in the work of the contractile elements of nerve cells: microfilaments, which ensures the movement of various substances in the body of the nerve cell, the axon and its growing tip. Protein kinase C is involved in protein phosphorylation reactions inside nerve cells. If these are enzyme proteins, then their activity changes; if these are ribosomal or nuclear proteins, then the rate of protein biosynthesis changes.

Lipids in nervous tissue are constantly renewed. Their update speed varies, but is generally low. Some lipids (for example: cholesterol, cerebrosides, phosphatidylethanolamines, sphingomyelins) are exchanged slowly - over several months and even years. The exception is phosphatidylcholine and, especially, phosphatidylinositols (contain glycerol, phosphate, alcohol (inositol, fatty acids) - they are exchanged very quickly (within days or weeks).

In the developing brain during the period of myelination, the synthesis of cerebrosides and gangliosides occurs at high speed. In adults, almost all cerebrosides (up to 90%) are found in myelin sheaths, and gangliosides are found in neurons. In this case, brain cells cannot use fatty acids for energy.

4. Metabolism of proteins and amino acids

Free amino acids in nervous tissue, or the so-called amino acid pool, have been the subject of careful study for many years. This is explained not only by the exclusive role of amino acids as a source of synthesis of a large number of biologically important compounds, such as proteins, peptides, some lipids, a number of hormones, vitamins, biologically active amines, etc. Amino acids or their derivatives are also involved in synaptic transmission, in the implementation of interneuronal networks as neurotransmitters and neuromodulators. Their energy significance is also significant, since the amino acids of the glutamic group are directly related to the tricarboxylic acid cycle. Brain tissue intensively exchanges amino acids with the blood. For this there are two special transport systems for uncharged ones and a few more - for amino acids having a positive or negative charge.

Up to 75% of the total number of amino acids in nervous tissue are aspartate, glutamate, as well as products of their transformations or substances synthesized with their participation (glutamine, acetyl derivatives, glutathione, GABA and others). Their concentration, and primarily glutamate, in nervous tissue is very high. For example, the concentration of glutamic acid can reach 10 mmol/l (A.Ya. Nikolaev, 2004).

Glutamic acid rightfully occupies a central place in the metabolism of amino acids in the brain. It is used to form glutathione, glutamine and gamma-aminobutyric acid. Glutamate is formed from its keto analogue - -ketoglutaric acid during the transamination reaction. The reaction of converting alpha-KG into glutamate occurs in brain tissue at high speed. The resulting glutamate is a by-product for the TCA cycle. The large consumption of alpha-CG is replenished due to the conversion of aspartic acid into the metabolite of the TCA cycle - PCHUK.

GABA, formed from glutamate, can be converted back into PIKE as a result of several reactions. This is how a GABA shunt is formed, which is present in the tissues of the brain and spinal cord. Therefore, in these tissues the content of GABA, as an intermediate metabolite of the cyclic process, is significantly higher than in others. Up to 20% of the total amount of glutamate is used here for the formation of GABA (Fig. 1). The remaining pathways of amino acid metabolism are similar to those found in other tissues. It is still unclear that the brain contains an almost complete set of ornithine cycle enzymes that do not contain carbamoyl phosphate synthase, so urea is not formed here.

Rice. 1. Scheme of GABA bypass (details in the text).

Brain tissue, like other tissues, is capable of synthesizing non-essential amino acids. Ammonia is constantly being formed here; its direct source is the deamination of AMP. The resulting ammonia binds to glutamate and leaves the brain in the form of glutamine. The primary sources of the amino group for the regeneration of AMP from IMP are various amino acids, and the intermediate carriers are glutamate and aspartate. Thus, the primary source of ammonia in the brain is amino acids.

Deamination is the process of donating an amino group to an acid, which is based on transamination, i.e. transfer of an amino group to some acceptor. The amino group of the amino acid is transferred to -ketoglutaric acid, which then becomes glutamic acid. Glutamic acid can transfer the amino group to some substances or release it in the form of ammonia. In the process of losing the amino group, glutamic acid becomes β-ketoglutaric acid again, and the cycle can be repeated again. After deamination of amino acids, the resulting keto acids can in most cases be oxidized, releasing energy for metabolic needs. In this case, two sequential processes are usually carried out: 1) keto acids are converted into chemicals that can be included in the citric acid cycle; 2) then these substances, broken down in the citric acid cycle, serve as a source of energy similar to acetyl CoA formed during the metabolism of carbohydrates. In general, the oxidation of 1 g of protein produces slightly less ATP than the oxidation of 1 g of glucose.

5. Features of nucleic acid metabolism.

Pyrimidines cannot be synthesized in nervous tissue cells (nervous tissue lacks the enzyme carbamoyl phosphate synthase). Pyrimidines must come from the blood - the BBB is permeable to them. The BBB is also easily permeable to purine mononucleotides, in contrast to pyrimidine mononucleotides, which can be synthesized in nervous tissue.

In nervous tissue, as well as in other tissues, nucleic acids ensure the storage and transmission of genetic information and its implementation during the synthesis of cellular proteins. For example, strong stimuli: loud sounds, strong visual stimuli and emotions lead to an increase in the rate of RNA and protein synthesis in certain areas of the brain. This indicates that changes in the nervous system, reflecting the individual experience of the organism, are encoded in the form of synthesized macromolecules.

The information through which neurons establish selective connections with certain neurons is encoded in the structure of the polysaccharide branches of membrane glycoproteins. The formation of such connections that were not laid down during the period embryonic development, is the result of an individual’s experience and constitutes the material basis for storing information that determines the behavioral characteristics of a given organism.

6. The role of water in ensuring the functioning of the brain

With dehydration of the body, the volume of cellular fluid first decreases, then extracellular fluid, and then water is removed from the bloodstream. This mechanism is designed to provide water to the brain, which contains about 75% water. Losing even 10% of water leads to serious consequences. The leading role of water for the brain of a child in the womb is emphasized by various researchers. The child is almost always upside down there. In this position, the blood supply to the brain improves, on which the entire subsequent life of a person depends during this period. Brain cells, which must constantly remove toxic products resulting from brain activity, are especially sensitive to a lack of water. In order for the brain to use the energy obtained from food, it must go through many intermediate reactions, which requires a sufficient amount of water, which in itself is not an energy product.

In addition, the brain is bathed in fluid produced by the brain's capillaries (cerebrospinal fluid contains more sodium and less potassium than all other fluids).

7. Chemical features of myelin

Nerve fibers are surrounded by a myelin sheath, which in the brain is formed by glial cells (oligodendroglial cells). Based on dry matter weight, the myelin sheath contains 70% lipids and 30% proteins. About 65% of all brain lipids are located in myelin sheaths (Table 2).

Myelin proteins, as a rule, are hydrophobic, do not dissolve in water, but form non-covalent compounds with membrane lipids. About 1/3 of all myelin proteins are water-soluble alkaline protein, called “encephalitis” protein.

Table 1.

Lipid composition of myelin in human nervous tissue

lipids
Cholesterol	27,7
Cerebrosides	22,7
Phosphatidylethanolamines	15,6
Phosphatidylcholines	11,2
Sphingomyelins
Phosphatidylserines
Plasmalogens	12,3

8. Providing energy for the conduction of excitation along the nerves.

The energy used to conduct a nerve impulse is a derivative of the potential energy stored as the difference in ion concentrations on either side of the nerve fiber membrane. Thus, a high concentration of potassium ions inside the fiber and a low concentration outside is a type of energy storage method. The high concentration of sodium ions on the outer surface of the membrane and the low concentration on the inside represent another example of energy storage. The energy required to conduct each action potential along the fiber membrane is a derivative of the stored energy when a small amount of potassium leaves the cell and a stream of sodium ions rushes into the cell. However, the active transport system provided by ATP energy returns the displaced ions to their original position relative to the fiber membrane.

For primary active transport, energy is extracted directly from the breakdown of adenosine triphosphate. The active transport mechanism is best studied for the sodium-potassium pump ( Na+/K+ - pump) transport process that “pumps” sodium ions out and “pumps” potassium ions into the cell. This mechanism is responsible for maintaining different concentrations of sodium and potassium ions on both sides of the membrane, as well as for the presence of a negative electrical potential inside cells. The carrier protein is a complex of two globular proteins: a larger one, called the -subunit, with a molecular weight of about 100,000, and a smaller one, called the -subunit, with a molecular weight of about 55,000. The large protein has three specific characteristics:

1) on the part of the protein facing the inside of the cell there are three receptor sites for binding sodium ions;

2) on the outer part of the protein there are two receptor sites for binding potassium ions;

3) the internal part of the protein, located near the sodium ion binding sites, has ATPase activity.

When two potassium ions bind to the outside of the carrier protein and three sodium ions bind to the inside, the ATPase function of the protein is activated. This leads to the breakdown of one ATP molecule into ADP, releasing energy. It is assumed that this energy causes a chemical and conformational change in the carrier protein molecule, resulting in the movement of ions.

Na+/K+ -ATPase can also work in the opposite direction. The relative concentrations of ATP, ADP and phosphates and the electrochemical gradients of sodium and potassium determine the direction of the reaction. In nerve cells, about 70% of all energy consumed is used to move sodium out and potassium into the cell. Na+/K+ - the pump is called electrogenic because it creates a transmembrane potential difference, i.e. creates an excess of positive charges on the surface of the cell, and the inside of the cell becomes negatively charged. The presence of electrical potential is the basis for signal transmission in nerve fibers.

Another important primary active transport mechanism is the calcium pump. One of them is located in the cell membrane and “pumps” calcium ions out of the cell. The other “pumps” calcium ions into the mitochondria. In each of these cases, the carrier protein penetrates the membrane and functions as an ATPase.

In the choroid plexus of the brain, substances must be transported not just through cell membrane, but through a layer of cells. The main mechanisms of transport through the cell layer are:

1) active transport through the cell membrane on one side of the transporting cells;

2) simple or facilitated diffusion through the membrane on the opposite side of these cells.

The amount of energy required to actively transport a substance across a membrane is determined by the degree of concentration of the substance during transport. The required energy is proportional to the decimal logarithm of the degree of concentration of the substance and is expressed by the following formula (1).

, (1)

where C 1 concentration of the substance outside the cell, C 2 - concentration of a substance inside the cell (According to A. Guyton and D. Hall, 2008).

In nerve fibers, information is transmitted through action potentials, which are rapid changes in membrane potential propagating along the fiber membrane. Local circular currents propagate from depolarized areas of the membrane to adjacent unexcited areas. These currents arise due to the transfer of positive electrical charges through the depolarized membrane in the form of sodium ions diffusing into the fiber, which then spread over several millimeters in both directions along the axon axis. As a result, sodium channels immediately open in these new areas, which underlies the propagation of the action potential. These newly depolarized areas enhance local circular currents flowing further along the membrane, gradually depolarizing more and more distant areas. Thus, the depolarization process spreads along the entire length of the fiber. This conduction of depolarization along a nerve fiber is called a nerve impulse.

Conducting each action potential along a nerve fiber slightly reduces the difference in the concentrations of sodium and potassium ions inside and outside the membrane. For a single action potential, these changes are so small that they cannot be measured. From 100 thousand to 50 million impulses can pass along a large nerve fiber before the concentration differences reach a level at which the conduction of the action potential stops. Over time, it becomes necessary to restore the difference in concentrations for ions on both sides of the membrane. This is ensured by work Na+/K+ - pump. Because this pump requires energy to operate, recharging the nerve fiber is an active metabolic process that uses the energy of ATP. Special property Na+/K+ - the pump is a sharp increase in the level of its activity when an excess of sodium ions appears inside the fiber. Pump activity increases in proportion to approximately the third degree of change in intracellular sodium ion concentration.

9. Cerebral energy metabolism in childhood

Studies of the dynamics of cerebral energy metabolism are based mainly on the analysis of changes in blood flow, the state of the BBB, and the metabolism of glucose and oxygen in humans.

The supply of energy substrates from the blood to the brain occurs through the BBB. The basic functions of the BBB are thought to mature during the prenatal period. More recently, evidence has emerged indicating a number of subtle changes in intracranial vascular resistance and changes in capillary size that occur during development in humans and animals.

The flow of glucose from the blood into the brain is associated with the development of a system of transport proteins, the main of which are GLUT 1 and GLUT 3 , localized in the BBB, as well as in neurons and glia. Studies in rats have shown that GLUT 1 with a molecular weight of 55 kDa is found in endothelial cells, GLUT 1 with a molecular weight of 45 kDa - in the non-vascularized brain, probably in glia; GLUT 3 is the main neuronal glucose transporter. Increased glucose utilization in the brain during brain maturation is closely related to the expression pattern of nonvascular GLUT 1 (45 kDa) and more specific GLUT 3 . Cellular expression of glucose transporter protein is hypothesized to be an indicator of glucose utilization in the developing rat brain.

In newborns, the intensity of glucose metabolism is low. Glucose metabolism in the brain of rat pups increases between 1 and 3 months of age, which approximately corresponds to the first decade of human life. Data were obtained on the peculiarities of changes in glucose metabolism in various structures of the human brain during development. The highest rate of glucose metabolism (GMR) in newborns occurs in the sensorimotor cortex, thalamus, brain stem and cerebellar vermis. During the first year of life, the SMG pattern changes in accordance with the maturation of phylogenetically younger structures. In the second and third months, the highest SMG is observed in the parietal, temporal, primary visual areas of the cortex, in the basal ganglia and cerebellar hemispheres. Glucose metabolism remains low in the dorsolateral visual cortex compared to the primary visual cortex. SMG is not high in the frontal areas until 2-4 months. By the end of the first year, the SMG pattern is qualitatively the same as in an adult, but quantitative changes occur throughout childhood. In the interval from 4 to 9 years, the highest values of SMG of the cortex and relatively young subcortical formations are observed, then at the end of the second decade of life, SMG decreases almost by half.

In early childhood, the central nervous system uses ketone bodies as an energy substrate in addition to glucose, which leads to acidification of the brain. For this reason, the relationship between the intensity of cerebral blood flow and glucose metabolism at this age is less than in an adult body.

As the brain develops and oxidative reactions intensify, the number of mitochondria per nerve cell doubles (N.D. Eshchenko, 1999). As the brain matures, the content of the main components of the mitochondrial respiratory chain increases 2-3 times: cytochromes and flavoproteins.

In the early stages of postnatal ontogenesis, the ability to maintain a constant pH is limited. It was shown that acute metabolic acidosis (or alkalosis), which was created in immature rats to test their ability to maintain pH in the brain, stabilized between 7.1 and 7.5 in the cortex one week after birth. At this age, the brain of rats was more resistant to the effects of metabolic acidosis than alkalosis.

The increase in cerebral blood flow and glucose metabolism occurs in parallel with an increase in the functional activity of the brain. It is assumed that the fast ascending part of the SMG curve is associated with overproduction of synapses and terminals, the plateau is associated with a period of increased energy requirements due to the active formation of synaptic contacts between neurons, the descending period is associated with selective reduction of synapses, during which a noticeable decrease in brain plasticity is observed.

10. Cerebral energy metabolism in middle age

and with aging.

Differences between men and women in the level of glucose consumption by the brain were studied. The results obtained are very ambiguous. Many studies have not found such differences, while a number of other studies have identified higher levels of glucose consumption in women. The authors attribute such differences to high estrogen levels, since the women were examined from days 5 to 15 of the menstrual cycle.

When examining healthy adult subjects, it was found that in a state of quiet wakefulness, the level of glucose consumption in both men and women was higher in the associative areas on the left, and in the limbic regions of the temporal lobe on the right. In men, metabolism in the limbic parts of the temporal lobe is higher, and in the cingulate gyrus, lower than in women.

The integrity of the cerebral vascular system is one of the decisive factors for the preservation of human cognitive functions in adulthood and aging. There is substantial evidence that cerebrovascular function declines with aging. Many authors have shown an age-dependent deterioration in blood flow due to atherosclerosis and loss of innervation of the basal surface of the cerebral arteries.

The main changes in the transport function of the BBB during aging are associated with restructuring in the composition of the connective tissue and smooth muscle of the vascular walls, thickening of the vascular basement membrane, thinning of the endothelium, an increase in pericytic glia and loss of endothelial mitochondria. These changes, in general, entail profound disturbances in the microvessels, the inclusion of foreign substances in the basement membrane and changes in the specific proteins and lipids that form it. With aging, focal and transient gaps in the BBB develop. Thus, neuronal populations in a certain region of the brain become vulnerable. In old age and senility, the effect of proteolytic enzymes on the basement membrane also increases, which increases the permeability of the BBB with an increase in the transcellular transport activity of endothelial cells.

At the same time, for a number of substances, the permeability of the BBB decreases with aging. A decrease in the transport of hexose and butyrate, choline and triiodothyronine was found. The transport of most neutral and basic amino acids is stable during aging. However, methionine transport assessed by positron emission tomography in humans decreases with age, starting at 5 years. A potential mechanism for age-dependent changes is associated with an increase in the number of arteriovenous anastomoses, which deprives some parts of the brain of sufficient nutrition. Changes in microvessels are also caused by a restructuring of the protein composition and accumulation of lipid peroxidation products along with a change in the viscosity of the membrane of isolated microvessels. The concentration of monoamine and purine metabolites and norepinephrine metabolism products depends on the intensity of energy metabolism; the latter have a strong effect on the permeability of the BBB. With aging, the neurotransmitter regulation of local cerebral blood flow also changes. Transmitter activity, especially beta-adrenergic neurotransmitters, decreases significantly in cerebral microvessels with aging. Many neurotransmitters do not pass well through the endothelial membrane and accumulate within the endothelium of brain capillaries. Capillary walls normally contain DOPA decarboxylase and monoamine oxidase, which break down neurotransmitters that act on blood vessels. With aging, this mechanism is disrupted.

Along with vascular system The cerebrospinal fluid (CSF) circulatory system also ages. In this case, the choroid plexus becomes calcified and CSF turnover decreases. The arachnoid membrane thickens, and as a result, contamination of the CSF with various metabolites occurs.

The permeability of the BBB can be affected by substances in the blood, as well as blood acidity. It was shown that when rats were given drugs that lowered blood pH, the entry of labeled sodium into the choroid plexus and CSF decreased. Acid salts were administered intraperitoneally to rats with removed kidneys, and the rate of entry of labeled sodium into various parts of the brain and into the CSF was determined. Severe acidosis (arterial pH 7.2) caused by hydrochloric acid injection reduced the rate of sodium entry into both CSF and brain tissue by approximately 25%, while mild acidosis (pH = 7.3) from injection N.H. 4 Cl decreased sodium intake into the brain by 18% and into the CSF by 10%. (V.A. Murphy and S. Johanson, 1989).

With aging, the transport of a number of substances to the brain decreases somewhat due to an increase in vascular resistance caused by atherosclerosis, the appearance of arteriovenous anastomoses and changes in the permeability of the BBB; the main substances easily reach the cells of the nervous tissue.

The average level of oxygen metabolism significantly decreases with aging. With age, this indicator decreases significantly in the cerebral hemispheres, and to a greater extent in the left. Particularly noticeable decrease in O metabolism 2 observed in the region of the left caudate nucleus. The pattern is so characteristic that in some cases the rate of O absorption 2 used to determine biological age.

Normal aging of the mammalian brain is associated with a number of genetic metabolic changes that include likely primary inherited variations in neuronal insulin receptors, desensitization of neuronal insulin receptors by circulating stress hormone cortisol, and subsequent receptor dysfunction due to changes in membrane structure and function. The consequences of even mild disturbances in glucose metabolism and energy production are associated with changes in homeostasis that are characteristic of the aging process. Due to shifts in glucose metabolism and energy production, deviations occur in the binding and release of acetylcholine, Ca metabolism 2+ etc. Additional formation of free radicals and structural changes in membranes are considered as primary changes during aging. Stress in old age causes more severe and long-lasting disturbances in homeostasis, affecting membranes.

Glucose hypometabolism can occur in humans and animals even with normal levels of cerebral blood flow. It has been shown that in rats older than 3 months, glucose consumption in many parts of the brain decreases, although blood flow remains normal up to 12 months. The disruption of the coupling of blood flow and glucose metabolism during aging compared to adulthood is due to the use of other substances, in particular ketone bodies, as an energy substrate, in addition to glucose. This change in energy metabolism is accompanied by a decrease in cerebral pH.

With aging, glucose consumption changes differently in different parts of the brain. The most typical hypometabolism of glucose is in the frontal areas. It has been shown that during normal aging, a relative decrease in energy metabolism in the frontal regions is covariately associated with an increase in metabolism in the parieto-occipital association areas, basal ganglia, midbrain and cerebellum. This profile was correlated with age. Glucose hypometabolism is observed in addition to the frontal areas and in other associative areas - the temporal, temporo-parietal areas, as well as in the anterior cingulate gyrus and anterior thalamus.

It was also found that with aging under conditions of quiet wakefulness, the correlation between the level of glucose consumption in the frontal and parietal regions of the brain decreases in both men and women.

With aging, changes occur in the oxygen and glycolytic pathways of glucose metabolism in humans and animals. The activity of many enzymes in the glycolytic pathway of glucose metabolism decreases. The content of the final product of glycolysis, lactate, in the brain of rats decreases at the ages of 24 and 30 months and corresponds to 91 and 87% of the level at a young age; at the age of 24 months, the pyruvate content decreases by 15% compared to 12-month-old animals.

Due to mitochondrial changes, disturbances occur in the oxygen pathway of glucose metabolism, and these deviations are more significant than in glycolysis. With aging, changes occur in the mitochondrial genome, which leads to disruption of the functional activity of mitochondria, a decrease in tissue respiration and oxidative phosphorylation.

The content of high-energy compounds (ATP and creatine phosphate) gradually decreases with age. Thus, the level of ATP in the brain of rats was 1.1 times lower at 12 months of age compared to 6 months of age; at 30 months the decrease was 6% of the level at 12 months. Creatine phosphate levels decreased in rats at 24 and 30 months of age to 93 and 90%, respectively, of their levels at 12 months.

In humans, the content of creatinine and creatine in the CSF, as indicators of brain energy metabolism (these substances are formed as a result of the breakdown of the high-energy compound creatine phosphate), also has a positive correlation with age.

With aging, the pH level in neurons decreases. This effect was found in studies of hippocampal slices in mice, and extracellular pH did not change with age. This pattern was subsequently confirmed when studying intracellular pH in the occipital regions using NMR spectroscopy in healthy people aged 23 to 69 years who were in a state of quiet wakefulness. It was also found that in people over 40 years of age, pH decreases immediately after photostimulation; this is not observed at a younger age. The development of intraneuronal acidosis during aging can disrupt the processes of tissue respiration and oxidative phosphorylation in mitochondria and contribute to increased free radical oxidation.

Literature

MAIN LITERATURE

Smirnov V.M., Budylina S.M. Physiology of sensory systems and higher nervous activity. M.: “Academy”. 2009. 336 p.

Smirnov V.M. et al. Physiology of the central nervous system. M.: “Academy”. 2008. 368 p.

Shulgovsky V.V. Fundamentals of neurophysiology. Textbook manual for university students. M.: “Aspect Press”. - 2005. 277 p.

ADDITIONAL LITERATURE.

Atlas. Human nervous system. Structure and disturbances. /Edited by V.M. Astapova, Yu.V. Mikaze. 4th ed., revised. and additional - M.: PER SE. - 2004. - 80 p.

Abrahams P. Physiology. M.: JSC BMM. 2008. 192 p.

Agadzhanyan N.A. Fundamentals of human physiology. - Textbook for university students. - 2nd ed. - M.: RUDN. - 2001.- 408 p.

Aleynikova T.V. et al. Physiology of the central nervous system. Rostov on Don: Phoenix. 2006. 376 p.

Luria A.R. Fundamentals of neuropsychology. - M.: “Academy”. 2009. 384 p.

Ashmarin I.P., Eshchenko N.D., Karazeeva E.P. Neurochemistry in tables and diagrams. M.: “Exam”. 2007. 143 p.

Beginnings of physiology. - Textbook for universities. / Ed. HELL. Nozdracheva. St. Petersburg. 2002. 1088 p.

Tevs G., Schmidt R. Human physiology in 3 volumes. M.: Mir. 2005. T.1.- 323 p.

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The main role of carbohydrates is determined by their energy function. And although the oxidation of 1 g of carbohydrates produces the same amount of energy as the oxidation of 1 g of protein (17.6 kJ), but due to the amount of carbohydrates consumed (the ratio of proteins, fats and carbohydrates is 1: 1: 4) and rapid mobilization blood glucose is a direct source of energy in the body. The speed of its disintegration and oxidation, as well as the possibility of rapid extraction from the depot, provide emergency mobilization of energy resources with rapidly increasing energy costs in cases of emotional arousal, intense muscle loads, etc.

The blood glucose level is 3.3-5.5 mmol/l (60-100 mg%) and is the most important homeostatic constant of the body. The central nervous system is especially sensitive to low blood glucose levels (hypoglycemia). Minor hypoglycemia is manifested by general weakness and fatigue. When the level of glucose in the blood decreases to 2.2-1.7 mmol/l (40-30 mg%), convulsions, delirium, loss of consciousness, as well as vegetative reactions develop: increased sweating, changes in the lumen of skin vessels, etc. called "hypoglycemic coma". The introduction of glucose into the blood quickly eliminates these disorders.

Changes in carbohydrates in the body. Glucose entering the blood from the intestines is transported to the liver, where glycogen is synthesized from it (Fig. 9.7).

Rice. 9.7.

Liver glycogen represents a reserve, i.e. stored in reserve, carbohydrate. Its amount can reach 150-200 g in an adult. The formation of glycogen with a relatively slow flow of glucose into the blood occurs quite quickly, so after the introduction of a small amount of carbohydrates, an increase in blood glucose (hyperglycemia) is not observed. If a large amount of easily broken down and quickly absorbed carbohydrates enters the digestive tract, the glucose level in the blood quickly increases. Developing at the same time hyperglycemia called alimentary, in other words, food. Its result is glucosuria, those. the release of glucose in the urine, which occurs if the level of glucose in the blood rises to 8.9-10.0 mmol/l (160-180 mg%).

In the complete absence of carbohydrates in food, they are formed in the body from the breakdown products of fats and proteins.

As the concentration of glucose in the blood decreases, glycogen is broken down in the liver and glucose enters the blood (glycogen mobilization). Thanks to this, the blood glucose level remains relatively constant.

Glycogen It is also deposited in the muscles, where it contains about 1-2%. The amount of glycogen in muscles increases during heavy meals and decreases during fasting. When muscles work under the influence of the enzyme phosphorylase, which is activated at the beginning of muscle contraction, increased breakdown of glycogen occurs, which is one of the sources of energy for muscle contraction.

The uptake of glucose by different organs from the incoming blood is not the same: the brain retains 12% of glucose, the intestines - 9%, muscles - 7%, kidneys - 5% (E.S. London).

The breakdown of carbohydrates in the body of animals occurs both in an oxygen-free way to lactic acid (anaerobic glycolysis), and by oxidation of carbohydrate breakdown products to carbon dioxide and water (aerobic way).

Regulation of carbohydrate metabolism. The main parameter for regulating carbohydrate metabolism is maintaining blood glucose levels within the range of 3.3-5.5 mmol/l. Changes in blood glucose levels are perceived by glucoreceptors, concentrated mainly in the liver and blood vessels, as well as by cells of the ventromedial hypothalamus. The participation of a number of parts of the central nervous system in the regulation of carbohydrate metabolism has been shown.

Claude Bernard showed back in 1849 that an injection of the medulla oblongata in the area of the bottom of the fourth ventricle (the so-called sugar injection) causes an increase in the glucose (sugar) content in the blood. With irritation of the hypothalamus, you can get the same hyperglycemia as with an injection into the bottom of the fourth ventricle. The role of the cerebral cortex in the regulation of blood glucose levels illustrates the development of hyperglycemia in students during exams, in athletes before important competitions, and also during hypnotic suggestion. The central link in the regulation of carbohydrate and other types of metabolism and the place of formation of signals that control glucose levels is the hypothalamus. From here, regulatory influences are realized by the autonomic nerves and the humoral pathway, including the endocrine glands (Fig. 9.8).

Insulin, a hormone produced by the 3-cells of the islet tissue of the pancreas, has a pronounced effect on carbohydrate metabolism. When insulin is administered, the level of glucose in the blood decreases. This occurs due to insulin enhancing the synthesis of glycogen in the liver and muscles and increasing glucose consumption by body tissues. Insulin is the only hormone that lowers blood glucose levels, therefore, with a decrease in the secretion of this hormone, persistent hyperglycemia and subsequent glycosuria develop ( diabetes, or diabetes diabetes).

Rice. 9.8.

An increase in blood glucose levels occurs under the action of several hormones: glucagon, produced by a-cells of islet tissue of the pancreas; adrenaline - adrenal medulla hormone; glucocorticoids - hormones of the adrenal cortex, which mainly cause the synthesis of carbohydrates from non-carbohydrate compounds - gluconeogenesis; growth hormone pituitary gland; thyroxine And triiodothyronine- thyroid hormones. Due to the unidirectionality of their influence on carbohydrate metabolism and functional antagonism in relation to the effects of insulin, these hormones are often combined with the concept "contrinsular hormones".