The concept of tissue respiration. stages of tissue respiration. composition and function of the respiratory chain of the inner mitochondrial membrane. Cellular respiration The role of oxygen in the process of tissue respiration

Oxygen transported in the blood is used to oxidize various substances to form CO2, water and other substances excreted in the urine as end products. The process of tissue absorption of oxygen associated with the formation of water and the release of carbon dioxide is tissue respiration.

The study of tissue respiration is carried out using the micromanometric method. Thin sections of tissue are placed in closed vessels connected to a narrow manometric tube filled with liquid. When determining the absorption of oxygen by tissue, an alkali solution is placed in one compartment of the vessel, which absorbs the released CO2. To achieve constant temperature, the vessels are immersed in a thermostat equipped with a heater and thermostat. Under these conditions, the decrease in the amount of gas, determined by the decrease in pressure in the vessel, will be equal to the amount of oxygen absorbed.

With the help of this kind of research, it is possible to obtain only approximate data to characterize tissue respiration occurring in the body. Tissue sections, being removed from the body, are deprived of the nervous regulation of their metabolism. They are placed in an environment that differs sharply from normal tissue fluid in terms of nutrient content and gas composition. Therefore, in order to transfer the results obtained in such experiments to tissues in their natural conditions of existence, it is necessary to conduct research on the whole organism. One of the ways to study tissue respiration of this kind is to study the gas composition and amount of blood flowing in and out of the organ under study.

During tissue respiration, substances that are usually resistant to molecular oxygen undergo rapid oxidation. They tried to explain this by assuming that oxygen in the tissues is activated. A theory has been developed according to which tissues contain substances (oxygenases) that can combine with molecular oxygen and produce peroxides. The latter, according to this theory, with the participation of special enzymes - peroxidases - oxidize one or another substrate. According to other ideas, oxygen and tissue respiration are activated by iron ions and iron-containing organic compounds.

A fundamentally new path for considering tissue oxidative processes was outlined by studies with plant tissues. The possibility of oxidative processes during tissue respiration and in the absence of molecular oxygen has been shown. The oxidizing substances in this case were respiratory pigments, derivatives of orthoquinone, capable of attaching two hydrogen atoms, turning into respiratory chromogens (diphenol derivatives). Further development of this concept of tissue respiration led to the establishment that the oxidation of a substrate begins with the removal of two hydrogen atoms from it. An oxidizing substance that donates hydrogen atoms is called a hydrogen donor, and an oxidizing substance that adds hydrogen is called a hydrogen acceptor.

The study of the physicochemical nature of oxidation processes during tissue respiration has shown that they are based on electron transfer. Typically, in biological systems, electrons are transferred together with protons, therefore, as part of hydrogen atoms. The final electron acceptor is oxygen. Oxygen, having accepted two electrons and attached two protons, forms a water particle with them. During oxidative processes, some organic acids undergo decarboxylation, i.e., due to their carboxyl group, CO2 is split off.

The transfer of hydrogen from the substrate to oxygen during tissue respiration, as a rule, occurs not directly, but with the participation of a number of intermediate enzymatic systems.

The first of these tissue respiration systems during the oxidation of substances such as phosphoglyceraldehyde, lactic acid, and citric acid is dehydrase. The dehydrase system includes codehydrase, which plays the role of a hydrogen acceptor.

The resulting reduced codehydrase cannot be directly oxidized by oxygen. It undergoes dehydrogenation by interacting with the flavin enzyme. The latter, in turn, is oxidized by one of the cytochromes during tissue respiration.

Cytochromes are iron-containing cellular pigments, with reduced cytochrome containing divalent iron in the hemin group, and oxidized cytochrome containing trivalent iron. The system of oxidative enzymes of tissue respiration also ends with an iron-containing enzyme - cytochrome oxidase, which oxidizes cytochromes and is capable of reacting directly with oxygen, which oxidizes the ferrous iron of this enzyme into ferric iron.

When a gram molecule of water is formed by the oxidation of two gram hydrogen atoms of the substrate, approximately 56 large calories (kcal) of energy are released. When hydrogen atoms pass through a number of intermediate enzymatic systems, this energy is split into smaller portions. The biological significance of this stepwise course of the oxidative process of tissue respiration is that the energy of oxidative processes is accumulated in the form of phosphate bond energy in the composition of adenosine triphosphoric (ATP) acid. Tissue oxidative processes are associated with phosphorylation processes, i.e., with the introduction of inorganic phosphoric acid into the composition of ATP. The last compound is a universal energetic substance. The energy accumulated in it is about 10 kcal per gram molecule of phosphoric acid. This energy is used during muscle contraction, during the synthesis of various substances (disaccharides, polysaccharides, hippuric acid, urea), during bioluminescence phenomena.

When one water molecule is formed, 3 or even 4 molecules of inorganic phosphoric acid are involved in an organic bond. Thus, three or even four stages during the transfer of two hydrogen atoms from one system to another are associated with phosphorylation phenomena.

In addition to the described main stages of tissue respiration, a number of other hydrogen carriers take a significant part in oxidative processes. Low molecular weight compounds include glutathione, polyphenols, ascorbic acid, and a system of dicarboxylic acids.

The article was prepared and edited by: surgeon

Tissue respiration is a set of reactions of aerobic oxidation of organic molecules in a cell, in which molecular oxygen is an obligatory substrate for the formation of oxidation products. However, oxygen can be used by a cell for different purposes:

1. in the inner membrane of mitochondria oxygen is the final acceptor of electrons from oxidizable substrates (NADH H + or FADH 2) with the possibility of including its active form (oxide anion; atomic oxygen) in a water molecule - one of the final products of the oxidation of organic molecules in aerobic cells;

2. monooxygenase systems of the inner membrane of mitochondria or membranes of the endoplasmic reticulum (ER) they use one atom of molecular oxygen to incorporate it into molecules of organic substrates in order to modify their structure and the appearance of such functional groups as hydroxyl, keto, aldehyde, carboxyl groups;

3. ER dioxygenase systems use two molecular oxygen atoms to form peroxide compounds such as R 2 O 2. The cell utilizes such peroxides thanks to antioxidant enzymatic systems: glutathione peroxidase, etc.

Problem 1 is performed by an aerobic cell mainly when energy-source substances appear in the cell, and there is a need for energy production by including these energy-source substances in catabolic pathways. Tissue respiration of a cell can be represented in the form of stages, there are three of them:

1st stage of tissue respiration - 2nd stage of catabolic processes;

Stage 2 of tissue respiration – Tricarboxylic Acid Cycle (TCA);

Stage 3 of tissue respiration is a function of the respiratory chain of the inner mitochondrial membrane.

The 1st and 2nd stages of tissue respiration produce reduced forms of coenzymes and prosthetic groups in the cytosol and matrix of mitochondria - potential electron donors to the respiratory chain of the inner mitochondrial membrane. It is in this membrane that there is a special complex of enzymes and lipophilic substances (ubiquinone; coenzyme Q), which transfers electrons from reduced forms of coenzymes (NADH) and prosthetic groups (FADH 2) to atomic oxygen.

The structure of mitochondria is divided into an outer membrane, an inner membrane, a matrix, and an intermembrane space. The processes of the first and second stages of tissue respiration are localized in the matrix and, partially, in the inner membrane: beta-oxidation of higher fatty acids, amino acid exchange reactions - oxidative deamination, transamination, Krebs cycle (TCC), with the exception of the succinate dehydrogenase reaction.

Both membranes are penetrated by transport systems responsible for:

1. transport of amino acids;

2. ATP/ADP transport;

3. ion transport;

4. shuttle systems (malate-aspartate, glycerol phosphate), transporting electrons and protons from the cytosolic forms of reduced coenzymes into the matrix and into the inner membrane;

5. transport of tricarboxylic acids;

6. transport of VZhK acyls;

7. transport of cations and anions.

Transport systems ensure the constancy of the composition of the mitochondrial matrix, the exchange of substances with the cytoplasm, and the delivery of the resulting substrates from the matrix to the cytoplasm for the needs of the cell.

The most important from an energetic point of view is the third stage of tissue respiration, i.e. function of the respiratory chain of the inner mitochondrial membrane. The respiratory chain consists of electron carriers from reduced forms of coenzymes to oxygen. Electron transporters are combined into complexes of the respiratory chain. The division of participants in the respiratory chain into complexes (I-IV) arose during experimental studies on the isolation and separation of components of the respiratory chain in order to study their structure and function.

Complex I of the respiratory chain consists of the transmembrane protein-enzyme NADH dehydrogenase (non-protein part - FMN) and iron-sulfur-containing proteins (FeS proteins). From the matrix, NADH forms migrate to the inner mitochondrial membrane, where they are captured by the flavoprotein NADH dehydrogenase. A redox reaction occurs:

NADH N + + FMN DGaza ® NAD + + FMN N 2 DGaza

FMN FMNN 2

The reduced form of NADH-DHase transfers electrons to ubiquinone (CoQ) through the FeS proteins of complex I, and ubiquinone can capture protons from the matrix:

KoQ KoQH 2

Ubiquinone is a very lipophilic structure that moves freely in the direction from the surface of the inner membrane facing the matrix (CoQH 2) to the surface of the inner membrane facing the intermembrane space (MMP) and back (CoQ). The reduced form of ubiquinone donates electrons to complex III of the respiratory chain, containing cytochromes V, from 1 and FeS proteins. Cytochromes V And from 1– hemoproteins of tertiary structure. A special feature of hemes is the presence of iron cations in them, which change the oxidation state Fe² + /Fe³ +. Heme cytochromes V , from 1 or With is able to accept only 1 ē, therefore, for the transfer of 2 ē, which are transported by the respiratory chain from the oxidized substrate (the reduced form of the coenzyme), two cytochromes of each type are needed. Cytochromes V , from 1 And With are not able to accept H + ions into their structure. The next electron acceptor is cytochrome With ( the most mobile cytochrome in the inner membrane; is not included in any complex), this is also a hemoprotein of tertiary structure.

Reduced form of cytochrome With(Fe² +) further donates electrons to cytochrome With-oxidase (COX). Cytochrome With-oxidase is a transmembrane protein, a hemoprotein of quaternary structure, consisting of six subunits: 4 A and 2 a 3, the latter contain only Cu² + /Cu + . This protein is also called complex IV of the respiratory chain. Cytochrome With-oxidase, receiving 4ē from cytochromes C (Fe² +), acquires a high affinity for molecular oxygen. Each pair of electrons goes to 1 atom of molecular oxygen to form an oxide anion, which combines with four protons to form endogenous water: 4H + +4 ē +O 2 → 2H 2 O

Tissue respiration and biological oxidation. The breakdown of organic compounds in living tissues, accompanied by the consumption of molecular oxygen and leading to the release of carbon dioxide and water and the formation of biological types of energy, is called tissue respiration. Tissue respiration is represented as the final stage in the transformation of monosaccharides (mainly glucose) to these end products, which at different stages includes other sugars and their derivatives, as well as intermediate products of the breakdown of lipids (fatty acids), proteins (amino acids) and nucleic bases. The final tissue respiration reaction will look like this:

С6Н12О6 + 6O2 = 6СО2+ 6Н2O + 2780 kJ/mol.

The respiratory chain includes three protein complexes (complexes I, III and IV), embedded in the inner mitochondrial membrane, and two mobile carrier molecules - ubiquinone (coenzyme Q) and cytochrome c.

The respiratory chain complexes are composed of many polypeptides and contain a number of different redox coenzymes associated with proteins (see pp. 108, 144). These include flavin [FMN (FMN) or FAD (FAD), in complexes I and II], iron-sulfur centers (in I, II and III) and heme groups (in II, III and IV). The detailed structure of most complexes has not yet been established.

Electrons enter the respiratory chain in various ways. During the oxidation of NADH + H+, complex I transfers electrons through the FMN and Fe/S centers to ubiquinone. The electrons formed during the oxidation of succinate, acyl-CoA and other substrates are transferred to ubiquinone by complex II or another mitochondrial dehydrogenase through the enzyme FADH2 or flavoprotein associated with the enzyme (see p. 166), while the oxidized form of coenzyme Q is reduced to aromatic ubihydroquinone. The latter transfers electrons to complex III, which supplies them through two heme b, one Fe/S center and heme c1 to the small heme-containing protein cytochrome c. The latter transfers electrons to complex IV, cytochrome c oxidase. To carry out redox reactions, cytochrome c oxidase contains two copper-containing centers (CuA and CuB) and hemes a and a3, through which electrons finally reach oxygen. When O2 is reduced, a strong basic anion O2- is formed, which binds two protons and passes into water. The flow of electrons is associated with the proton gradient formed by complexes I, III and IV.

26. Conversion of carbohydrates in the body. Digestion of carbohydrates in the digestive tract. Glycogen formation.

Carbohydrate conversions

The process of converting carbohydrates begins with their digestion in the oral cavity under the influence of saliva, then continues for some time in the stomach and ends in the small intestine - the main place of hydrolysis of carbohydrates under the influence of enzymes contained in the digestive juice of the pancreas and small intestine. The products of hydrolysis - monosaccharides - are absorbed in the intestine and enter the blood of the portal vein, through which food monosaccharides enter the liver, where they are converted into glucose. Glucose then enters the blood and can enter into processes occurring in cells or passes into liver glycogen.

Digestive juices lack the enzyme cellulase, which hydrolyzes cellulose supplied with plant foods. However, there are microorganisms in the intestines whose enzymes can break down some cellulose. In this case, the disaccharide cellobiose is formed, which then breaks down to glucose.

Uncleaved cellulose is a mechanical irritant of the intestinal wall, activates its peristalsis and promotes the movement of food mass.

Under the influence of microbial enzymes, the breakdown products of complex carbohydrates can undergo fermentation, resulting in the formation of organic acids, CO2, CH4 and H2.

First of all, glucose undergoes phosphorylation with the participation of the enzyme hexokinase, and in the liver - glucokinase. Next, glucose-6-phosphate, under the influence of the enzyme phosphoglucomutase, is converted into glucose-1-phosphate:

The resulting glucose-1-phosphate is already directly involved in glycogen synthesis. At the first stage of synthesis, glucose-1-phosphate interacts with UTP (uridine triphosphate), forming uridine diphosphate glucose (UDP-glucose) and pyrophosphate. This reaction is catalyzed by the enzyme glucose-1-phosphate uridylyltransferase (UDPG-pyrophosphorylase):

Glucose-1-phosphate + UTP< = >UDP-glucose + Pyrophosphate.

Here is the structural formula of UDP-glucose

Stages of glycogen formation - the transfer of the glucose residue included in UDP-glucose to the glucoside chain of glycogen (“seed” amount) occurs. In this case, an α-(1–>4) bond is formed between the first carbon atom of the added glucose residue and the 4-hydroxyl group of the glucose residue of the chain. This reaction is catalyzed by the enzyme glycogen synthase. It must be emphasized once again that the reaction catalyzed by glycogen synthase is possible only if the polysaccharide chain already contains more than 4 D-glucose residues. The resulting UDP is then phosphorylated back into UTP at the expense of ATP, and thus the entire cycle of glucose-1-phosphate conversion begins all over again.

Tissue respiration is a complex of redox reactions occurring in cells with the participation of oxygen. The oxidation process is accompanied by the release of electrons, and the reduction process is accompanied by their addition. In the role of an electron acceptor, i.e. the oxidizing agent is oxygen, so the basic equation for the reaction of consumption of 0 2 in the cells of aerobic organisms will be

This reaction is well known to everyone as the reaction of the explosion of detonating gas, which releases a significant amount of energy. In living systems, of course, an explosion does not occur, since hydrogen is not present in them in free molecular form, but is part of organic compounds and does not join oxygen immediately, but gradually through a number of intermediate carriers - respiratory enzymes. The released energy in such a system is stored in the form of a proton concentration gradient.

Enzymes of the class of oxidoreductases act as catalysts for tissue respiration processes. These enzymes are located on the folds of the inner mitochondrial membrane, where the final reaction occurs - the formation of water.

Respiratory enzymes are arranged on the membrane in an orderly manner, forming four multienzyme complexes (Fig. 3.13).

Rice. 3.13. The sequence of inclusion of enzymatic complexes (1-4) in the process of tissue respiration:

abbreviations are explained in the text

Small organic molecules act as hydrogen carriers in them: unphosphorylated and phosphorylated nicotinamide adenine dinucleotide (NAD+, NADP) - derivatives of nicotinic acid (vitamin PP); flavin adenine dinucleotide and flavin mononucleotide (FAD, FMN) are derivatives of riboflavin (vitamin B 2); ubiquinone, highly soluble in membrane lipids (coenzyme Q) and a group of heme-containing proteins (cytochromes a, a 3, b, c). An important role in the electron transport chain of mitochondria is played by iron, which is part of the heme cytochromes and the FcS complex, as well as copper.

The mitochondrial respiratory chain is completed by a reaction catalyzed by the enzyme cytochrome c oxidase, in which electrons are transferred directly to oxygen. An oxygen molecule accepts four electrons and two water molecules are formed.

The transfer of electrons along the respiratory chain is accompanied by the pumping of protons from the mitochondrial matrix into the intermembrane space and the formation of a transmembrane proton gradient on the inner membrane. This gradient is used by ATP synthase (an enzyme complex) to synthesize ATP from ADP (see also Vol. 1, Ch. 1).

The passage of four protons through the inner mitochondrial membrane along the electrochemical gradient is sufficient for the synthesis and transfer of one ATP molecule from the mitochondrion to the cytoplasm. Since during the formation of two water molecules 20 protons are transferred into the intermembrane space, the energy thus stored is sufficient for the synthesis of five ATP molecules. There is also a shortened path, when 12 protons are transferred and three ATP molecules are synthesized.

The described mechanism is the main pathway for ATP synthesis by cells under aerobic conditions and is called oxidative phosphorylation(Fig. 3.14).

Rice. 3.14.

1-4 - enzyme complexes of the electron transport chain

The energy of electron transfer can be used not to synthesize ATP, but to generate heat. This effect is called uncoupling of oxidative phosphorylation and is normally observed in brown adipose tissue. The role of the uncoupler in it is taken on by a special protein called thermogenin.

The addition of four electrons to an oxygen molecule results in the formation of water. The transfer of fewer electrons causes the formation of reactive oxygen species (ROS): if only one electron is added, a superoxide radical ion is formed, if two electrons are formed, a peroxide radical ion is formed, if three electrons are formed, a hydroxyl radical ion is formed. All of these radicals are unusually chemically active and can have damaging effects on the cell (especially in terms of membrane destruction). In addition to mitochondria, ROS can be produced by other enzyme systems in the membranes of the endoplasmic reticulum. In a healthy body, the formation of ROS is controlled by various antioxidant systems: enzymatic and non-enzymatic. The enzymatic system consists of enzymes such as superoxide dismutase, catalase, glutathione peroxidase and others, and the non-enzymatic system consists of vitamins E, C, A, uric acid and a number of other substances.

ROS not only damage cells, but can also perform a protective function. For example, macrophages use the production of ROS to destroy phagocytosed microorganisms.

Tissue breathing(synonymous with cellular respiration) is a set of redox processes in cells, organs and tissues that occur with the participation of molecular oxygen and are accompanied by the storage of energy in the phosphoryl bond of ATP molecules. Tissue respiration is the most important part metabolism and energy in organism. As a result, D. t. with the participation of specific enzymes oxidative decomposition of large organic molecules - substrates of respiration - occurs into simpler ones and, ultimately, into CO 2 and H 2 O with the release of energy. The fundamental difference between aerobic aerobic processes and other processes that involve the absorption of oxygen (for example, lipid peroxidation) is the storage of energy in the form of ATP, which is not typical for other aerobic processes.

The process of tissue respiration cannot be considered identical to the processes of biological oxidation (enzymatic processes of oxidation of various substrates that occur in animal, plant and microbial cells), since a significant part of such oxidative transformations in the body occurs under anaerobic conditions, i.e. without the participation of molecular oxygen, unlike D. t.

Most of the energy in aerobic cells is generated due to D. t., and the amount of energy generated depends on its intensity. D.'s intensity is determined by the rate of oxygen absorption per unit mass of tissue; Normally, it is determined by the tissue’s need for energy. D.'s intensity is highest in the retina, kidneys, and liver; it is significant in the intestinal mucosa, thyroid gland, testicles, cerebral cortex, pituitary gland, spleen, bone marrow, lungs, placenta, thymus gland, pancreas, diaphragm, heart, skeletal muscle at rest. In the skin, cornea and lens of the eye, the intensity of D. t. is low. Hormones thyroid gland, fatty acid and other biologically active substances can activate tissue respiration.

D.'s intensity is determined polarographically (see. Polarography ) or by the manometric method in the Warburg apparatus. In the latter case, to characterize D. t., the so-called respiratory coefficient is used - the ratio of the volume of carbon dioxide released to the volume of oxygen absorbed by a certain amount of the tissue being studied over a certain period of time.

D.'s substrates are the products of the transformation of fats, proteins, and carbohydrates (see. Nitrogen exchange, Fat metabolism, Carbohydrate metabolism ), coming from food, from which, as a result of appropriate metabolic processes, a small number of compounds are formed that enter the tricarboxylic acid cycle - the most important metabolic cycle in aerobic organisms,

in which the substances involved undergo complete oxidation. The tricarboxylic acid cycle is a sequence of reactions that combine the final stages of the metabolism of proteins, fats and carbohydrates and provide reducing equivalents (hydrogen atoms or electrons transferred from donor substances to acceptor substances; in aerobes, the final acceptor of reducing equivalents is oxygen) to the respiratory chain in mitochondria ( mitochondrial respiration). In mitochondria, a chemical reaction occurs in the reduction of oxygen and the associated storage of energy in the form of ATP, formed from ADP and inorganic phosphate. The process of synthesizing an ATP or ADP molecule using the oxidation energy of various substrates is called oxidative or respiratory phosphorylation. Normally, mitochondrial respiration is always associated with phosphorylation, which is associated with the regulation of the rate of oxidation of nutrients by the cell’s need for useful energy. With certain effects on the body or tissues (for example, during hypothermia), the so-called uncoupling of oxidation and phosphorylation occurs, leading to the dissipation of energy, which is not fixed in the form of a phosphoryl bond of the ATP molecule, but takes the form of thermal energy. Thyroid hormones, fatty acids, 2,4-dinitrophenol, dicoumarin and some other substances also have an uncoupling effect.

Tissue respiration is energetically much more beneficial for the body than anaerobic oxidative transformations of nutrients, for example