Breath. Aerobic oxidation of carbohydrates occurs in the presence of atmospheric oxygen, which is why it is often called respiration.
In contrast to glycolysis (glycogenolysis), where provine acid serves as the final acceptor of hydrogen atoms and electrons, during respiration oxygen plays the role of such an acceptor. In the first case, lactic acid is formed as the final product, in which the total oxidation state of carbon remains the same as that of glucose; in the second case, carbon dioxide is formed - a much simpler compound in which the only carbon atom is completely oxidized. At the same time, respiration and glycolysis have many common links.
Respiration, like glycolysis, is accompanied by the formation of phosphoric esters of glucose and fructose, phosphotriose-dioxyacetone phosphate and glyceraldehyde-3-phosphate, as well as intermediate products such as 1,3-diphosphoglyceric acid, 3-phosphoglycerate, phosphoenolpyruvate pyruvic acid. Many reactions of glycolysis and respiration are catalyzed by the same enzymes. In other words, during respiration, the conversion of glucose to lactic acid goes through all the same stages as during glycolysis. However, in this case, the hydrogen atoms split off from glyceraldehyde-3-phosphate do not reduce pyruvic acid, but are transferred to oxygen, passing through a complex system of enzymes of the respiratory chain.
Lactic acid, formed during the process of glycolysis, as already mentioned, still contains a fairly significant reserve (approximately 93%) of potential energy. However, despite this, the first living organisms that extracted energy under anaerobic conditions released it into the environment.
With the advent of oxygen in the Earth's atmosphere, living organisms developed new, more advanced oxidation mechanisms, as a result of which the amount of energy released was much greater than during glycolysis, since the final product of respiration is CO 2, the carbon atom of which is completely oxidized. Along with this, nature has created new mechanisms for the additional oxidation of the final product of glycolysis, which is released into the environment. In other words, it seemed to create a superstructure over glycolysis for the oxidation of its final product under aerobic conditions, keeping many of its stages the same.
Lactic acid is not produced during respiration. Therefore, pyruvic acid is the common substrate, or central link, where glycolysis ends and respiration begins (or the paths of glycolysis and respiration - anaerobic and aerobic oxidation of glucose - diverge).
Having retained the previous stages of glycolysis, the cells of the human body and higher animals retained the ability to oxidize glucose under anaerobic conditions, as a result of which, when there is a lack of oxygen, they are able to obtain energy in this way. However, in this case, lactic acid formed under anaerobic conditions, which has a fairly large reserve of energy, is not released into the environment, but accumulates in the muscles. From the muscles it is delivered by the bloodstream to the liver, where it is again converted into glucose. When a sufficient amount of oxygen enters the cell, part of the lactic acid is oxidized further to CO 2 and H 2 O.
Conversion of lactic acid. Lactic acid formed during the anaerobic oxidation of glucose is oxidized to CO 2 and H 2 O as follows. First, under the action of an enzyme lactate dehydrogenase, the coenzyme of which is NAD, it is oxidized to pyruvic acid:
which is then influenced pyruvate decarboxylase, which is a complex multienzyme complex, undergoes oxidative decarboxylation to form the active form of acetic acid - acetyl-CoA:
where TPP is thiamine pyrophosphate; LA - lipoic acid; HSKoA - coenzyme A.
In the case when the tissues are well supplied with oxygen, pyruvic acid undergoes oxidative decarboxylation immediately, without being reduced to lactic acid. The reduced coenzyme NAD H + H +, formed during the oxidation of glyceraldehyde-3-phosphate, transfers hydrogen through aerobic metabolic enzymes (i.e., the respiratory chain) to oxygen, forming water.
The conversion of pyruvic acid to acetyl-CoA is a preparatory, or transitional, stage, due to which carbohydrates, through pyruvic acid, and then through acetyl-CoA, are included in a new stage - oxygen oxidation. In other words, this process is the link between glycolysis and respiration itself. However, as a result of the oxidative decarboxylation of pyruvic acid to acetyl-CoA, about 9% of the total energy of glucose oxidation is released, i.e. more than during glycolysis in general, where only 5-7% of energy is released. If we take into account 5-7 % energy of glycolysis and 9% of the energy of oxidative decarboxylation of pyruvic acid, then a total of 14-16% of the energy accumulated in carbohydrates is released. Therefore, the remaining 84-86 % energy is still stored in the acetic acid molecule.
The tricarboxylic acid cycle (Krebs cycle) is a new, more advanced mechanism for the oxidation of carbohydrates, developed in living organisms with the appearance of oxygen on Earth. Using this mechanism, acetic acid is further converted in the form of acetyl-CoA to CO 2 and H 2 O under aerobic conditions with the release of energy.
Due to the fact that the first substrates in the oxidation of acetic acid are tricarboxylic acids, and the hypothesis about the mechanism of this oxidation was put forward by H. A. Krebs, the process was called the tricarboxylic acid cycle, or the Krebs cycle.
The first reaction of the cycle is the condensation reaction of acetyl-CoA with oxaloacetic acid, which is catalyzed by the enzyme citrate synthase. As a result, the active form of citric acid is formed - citril-CoA:
When hydrolyzed, citril-CoA is converted into citric acid:
The latter is under the action of an enzyme aconitate hydratase turns into cis-aconitic acid, which, adding water, turns into isocitric acid:
Isocitric acid is further oxidized by the elimination of two hydrogen atoms, turning into oxalosuccinic acid. This reaction begins the elimination of CO 2 and the first oxidation of acetyl-CoA in the tricarboxylic cycle. Oxalic-succinic acid, decarboxylated, turns into α-ketoglutaric acid. Dehydrogenation of isocitric and decarboxylation of oxalic-succinic acids is catalyzed by the enzyme isocitrate dehydrogenase with the participation of the coenzyme NAD +:
The next stage of the tricarboxylic acid cycle is the oxidative decarboxylation reaction of α-ketoglutaric acid, which results in the formation of succinic acid. This process occurs in two stages. First, α-ketoglutaric acid undergoes oxidative decarboxylation to form the active form of succinic acid - succinyl-CoA - and CO 2. This reaction resembles the reaction of the conversion of pyruvic acid to acetyl-CoA and is also catalyzed by a complex multienzyme complex - α -ketoglutarate dehydrogenase. As a result of this reaction, a second elimination of carbon dioxide occurs and the dehydrogenation of acetic acid entering the cycle:
The resulting active form of succinic acid, succinyl-CoA, in contrast to acetyl-CoA, is a high-energy thioether compound in which the energy of oxidation of α-ketoglutaric acid is accumulated.
In the next step, this energy is used to form GTP (guanosine triphosphoric acid) from GDP and inorganic phosphoric acid and is stored in the phosphate bonds of this compound. The reaction is catalyzed by an enzyme succinylthiokinase:
The GTP formed as a result of this reaction interacts with ADP, resulting in the formation of ATP:
GTP + ADP GDP + ATP.
ATP synthesis coupled with substrate oxidation is another example of substrate phosphorylation.
In the further course of the tricarboxylic acid cycle, two more dehydrogenations occur. Succinic acid under the influence succinate dehydrogenase with the participation of the coenzyme FAD + splits off two hydrogen atoms and turns into fumaric acid, and FAD + is reduced to FAD H 2. Then fumaric acid, adding a water molecule, forms malic acid (malate), which, with the help of malate dehydrogenase and the coenzyme NAD + undergoes dehydrogenation again. In this case, oxalic-acetic acid is formed, i.e. the substrate from which the tricarboxylic acid cycle begins:
The regenerated oxaloacetic acid can react again with a new acetyl-CoA molecule, and the process will begin in the same order.
The general scheme of the tricarboxylic acid cycle can be represented as follows:
Tricarboxylic acid cycle
(the end products of acetyl-CoA oxidation are shown in the box).
From the above diagram it follows that the main function of the Krebs cycle is the dehydrogenation of acetic acid. If we balance the enzymatic dehydrogenation of one cycle, we can easily calculate that the reactions produce eight hydrogen atoms: six atoms are used to reduce NAD + and two are used to reduce FAD + succinate hydrogenase.
The overall reaction of this cycle is described by the following equation:
CH 3 COOH + 2H 2 O → 2CO 2 + 8H,
from which it follows that four hydrogen atoms belong to water. Consequently, the remaining four were formed by dehydrogenation of acetic acid, i.e. this is all the hydrogen that was part of its molecule. At the same time, two carbon atoms were released twice in the form of carbon monoxide (IV) (once during the decarboxylation of oxalic-succinic acid, the second during the decarboxylation of α-ketoglutaric acid), i.e. exactly as many of them entered the cycle in the form of an acetal group.
It also follows from the above equation that neither oxygen, nor ATP, nor inorganic phosphoric acid are involved in the cycle. All these metabolites interact in the respiratory chain, which involves inorganic phosphoric acid, hydrogen atoms and oxygen removed during dehydrogenation, and ATP is formed as a result of oxidative phosphorylation. The energy for this process is released as a result of redox reactions when hydrogen atoms and electrons are transferred from the reduced forms NAD H 2 and FAD H 2 to oxygen.
The process of oxidative phosphorylation is described in detail in Chap. 22. Let us only recall that for every pair of electrons (a pair of hydrogen atoms) in the respiratory chain, three ATP molecules are formed by oxidative phosphorylation (one when transferring hydrogen atoms from NAD H + H + to FAD, the second when transferring a pair of electrons from cytochrome b to cytochrome With and the third - from cytochrome a 3 to the oxygen atom). Thus, each oxidative stage of the conversion of glucose to CO 2 and H 2 O, associated with NAD, is accompanied by the formation of three ATP molecules, associated with FAD - the formation of two ATP molecules.
Energy balance of carbohydrate oxidation. First, let's summarize the energy balance due to the dehydrogenation of acetic acid in the Krebs cycle. As we have already established, in this cycle four dehydrogenations occur, as a result of which three reduced forms of NAD and one FAD were formed, and one ATP molecule was synthesized by substrate phosphorylation:
Thus, the Krebs cycle synthesizes six times more ATP than glycolysis. If we take into account two more reduced NAD molecules formed during the oxidation of lactic and pyruvic acids, then this will amount to 6 more ATP molecules, and a total of 18. Since glucose breaks down into two phosphotrioses, the amount of ATP increases by 2 times and will amount to 36 molecules.
Adding to this 2 ATP molecules formed during glycolysis, we obtain the total balance of energy accumulated in the macroergic bonds of ATP during the oxidation of glucose to CO 2 and H 2 O: 36 + 2 = 38.
It has been established that the complete oxidation of 1 mole of glucose to CO 2 and H 2 O is accompanied by the release of 2872 kJ. 38 ATP molecules accumulate 1270-1560 kJ, i.e. approximately 50% of the total energy released during oxidation. Therefore, the remaining 50 % Energy is dissipated in the body in the form of heat to maintain an appropriate temperature.
Of the considered phases of glucose oxidation, the aerobic phase is of exceptional importance. If during anaerobic oxidation, i.e. during the formation of lactic acid, only 197 kJ of energy is released, of which 40 % accumulates in the high-energy bonds of two ATP molecules, then 2872 - 197 = 2675 kJ are released in the aerobic phase, which is about 93% of the total energy. Thus, the body receives the bulk of its energy through breathing.
Apotomic path glucose oxidation. Along with the Krebs cycle, in many cells there is another pathway for the breakdown of glucose, called apotomical, or pentose phosphate. It has been experimentally established that under aerobic conditions in erythrocytes, liver, and kidneys, glucose can be oxidized to 6-monophosphogluconic acid, and fructose-1,6-diphosphate is not formed in this process. As a result of this oxidation of glucose, a significant amount of pentoses is formed. This pathway was discovered by the Soviet biochemist V.A. Engelhardt, and its individual stages were studied by O. Warburg, F. Dickens, I.D. Golovatsky and others. The pentose phosphate pathway is not the main pathway of glucose oxidation. Its main purpose is to supply cells with reduced forms of NADP necessary for the biosynthesis of fatty acids, cholesterol, purine and pyrimidine bases, steroids, etc. The second function of this pathway is that it supplies pentoses, mainly D-ribose, for the synthesis of nucleic acids.
The pentose phosphate pathway for the breakdown of glucose can be summarized by the following equation:
Glucose-6-monophosphate + 2 NADP + → Ribose-5-monophosphate + CO 2 + 2 NADP·H + H + + 2H + .
Pentoses not used for the biosynthesis of nucleic acids and nucleotides are spent on the biosynthesis of other compounds and glucose regeneration.
Biosynthesis of carbohydrates
There are two main methods for the biosynthesis of carbohydrates from relatively simple metabolites. One of them is to reduce carbon dioxide to glucose. This process, characteristic of green plants and called photosynthesis, is carried out due to the energy of sunlight with the help of chlorophyll according to the following equation:
CO 2 + 2H 2 O 1/6C 6 H 12 O 6 + O 2 + H 2 O.
By capturing the sun's rays and converting their energy into carbohydrate energy, green plants ensure the preservation and development of life on Earth. This, according to K. A. Timiryazev, is the cosmic role of green plants as an intermediary between the sun and all life on Earth.
Recently, the work of a group of scientists from the Institute of Biochemistry. A. V. Palladin of the Academy of Sciences of the Ukrainian SSR, under the leadership of Academician M. F. Guly, showed that the tissues of higher animals are also capable of fixing carbon dioxide, although the mechanism of its fixation differs from that of photosynthetic cells. It consists in building up the carbon skeleton with carbon monoxide (IV) of substrates such as keto acids, fatty acids, amino acids, etc.
In the liver, kidneys and skeletal muscles of humans and higher animals, there is another pathway for the biosynthesis of carbohydrates, called gluconeogenesis. This is the synthesis of glucose from pyruvic or lactic acid, as well as from the so-called glycogenic amino acids, fats and other precursors, which during metabolism can be converted into pyruvic acid or metabolites of the tricarboxylic acid cycle.
Gluconeogenesis is the opposite pathway to glycolysis. However, there are three steps in this pathway that cannot be energetically used in the conversion of pyruvic acid to glucose. These three stages of glycolysis are replaced by "bypass" reactions that require less energy.
The first bypass reaction is the conversion of pyruvic acid to phosphoenolpyruvic acid. Since the breakdown of glucose occurs in mitochondria, and synthesis in the cytoplasm, at the first stage, mitochondrial pyruvic acid is first converted into oxalic-acetic acid. This transformation is catalyzed by an enzyme pyruvate carboxylase, activated by acetyl-CoA with the participation of ATP. The resulting oxalic-acetic acid is then reduced with the participation of NAD H + H + into malic acid:
Pyruvic acid + CO 2 Oxalacetic acid 
Apple acid.
Malic acid diffuses into the cytoplasm and is oxidized by cytoplasmic malate dehydrogenase to form cytoplasmic oxaloacetic acid, from which phosphoenolpyruvic acid is formed. This reaction is catalyzed phosphoenolpyruvate carboxykinase. GTP serves as a phosphoric acid donor:
Apple acid 
Oxalic acetic acid Phosphoenolpyruvic acid.
This is followed by a whole series of reverse reactions, ending with the formation of fructose-1,6-bisphosphate. The conversion of fructose-1,6-bisphosphate to fructose-6-phosphate is the second irreversible reaction of glycolysis. Therefore, it is catalyzed not by phosphofructokinase, but fructose diphosphatase. This enzyme catalyzes the irreversible hydrolysis of the 1-phosphate group:
Fructose-1, 6-diphosphate + H 2 O → Fructose-6-phosphate + H 3 PO 4.
At the next (reversible) stage of glucose biosynthesis, fructose-6-phosphate is converted into glucose-6-phosphate under the influence of phosphogluco-isomerase glycolysis.
The breakdown of glucose-6-phosphate to glucose is a third irreversible reaction that is not accomplished by reversal by hexokinase. Free glucose is formed by glucose-6-phosphatase, catalyzing the hydrolysis reaction:
Glucose-6-phosphate + H 2 O → Glucose + H 3 PO 4.
In most cells, glucose-6-phosphate, formed during glycogenolysis, is used as a precursor for the biosynthesis of oligo- and polysaccharides. A major role in the biosynthesis of these complex sugars is played by the compound uridine phosphoglucose, which acts as an intermediate glucose transporter.
During the biosynthesis of glycogen, for example, glucose-6-phosphate, converted into glucose-1-phosphate under the action of phosphoglucomutase, interacts with uridine triphosphoric acid (UTP), a compound similar to ATP, which contains the nitrogenous base uracil instead of adenine. As a result of this interaction using glucose-I-phosphate uridyltransferase uridyl diphosphoglucose is formed:
Glucose-1-phosphate + UTP UDP-glucose + Fn.
At the final stage of glycogen biosynthesis in a reaction catalyzed glycogen synthetase, the glucose residue from UDP-glucose is transferred to the terminal glucose residue of the amylase chain to form a 1,4-glycosidic bond (see Chapter 16). Branching of glycogen by formation of 1,6-bonds is completed amylo-1,4-1,6-transglucosidase.
Glycogen biosynthesis is carried out not only from glucose-6-phosphate, formed by gluconeogenesis. As noted above, part of the glucose after absorption is also used for its biosynthesis. Glycogen synthesis, as a process of formation of a mobile reserve of carbohydrates in the body, is of great biological importance. The leading role in this belongs to the liver. Thanks to the synthesis and deposition of glycogen in the liver, a constant concentration of glucose in the blood and other tissues is maintained, and its loss in the urine when eating food, especially carbohydrates, is prevented. In addition, the deposition of glycogen in the liver promotes the gradual use of carbohydrates depending on the living conditions of the body.
The use of glucose for glycogen synthesis is preceded by the formation of glucose phosphorus esters. First, glucose-6-monophosphate is formed. The source of energy and donor of phosphate is ATP. Hexokinase catalyzes this reaction. Under the action of the enzyme phosphoglucomutase, glucose-6-monophosphate is converted to glucose-1-monophosphate:
Further conversion of glucose-1-monophosphate to glycogen occurs in a way that is already familiar to us.
Chapter 24. LIPID METABOLISM
Lipids are a large group of organic compounds. They all differ in their chemical composition and structure, but have one common property - insolubility in water. Due to the fact that the enzymes acting on these organic compounds are water-soluble, the breakdown and absorption of lipids in the alimentary canal is characterized by certain features. The presence of lipids of different structures determines different ways of their breakdown and synthesis.
Let us dwell on the metabolism of fats, phosphatides and sterides, which have the most important biological significance.
Lipid metabolism, like carbohydrates, is a multi-stage process that consists of digestion, absorption, lipid transport in the blood, intracellular oxidation and biosynthesis.
Digestion of lipids
Digestion of triglycerides. Triglycerides, or neutral fats, are concentrated sources of energy in the body. When 1 g of fat is oxidized, about 38.9 kJ of energy is released. Being hydrophobic compounds, fats are stored in a compact form, taking up relatively little space in the body. Together with food, the human body receives up to 70 g of fats of plant and animal origin every day. By their chemical nature they are mainly triglycerides.
The breakdown of fats occurs with the help of enzymes called lipases. Saliva does not contain such enzymes, so fats do not undergo any changes in the oral cavity. In the stomach, lipase activity is very weak. This is due to the fact that in the stomach the reaction environment is strongly acidic (pH = 1.5-2.5), while the optimum action of lipase is at pH = 7.8 = 8.1. In this regard, only 3-5% of incoming fats are digested in the stomach.
Digestion of fats in the stomach occurs only in newborns and infants. This is due to the fact that the pH of the environment in the stomach of newborns is 5.6, and under these conditions lipase exhibits greater activity. In addition, the fat in mother's milk, which is the main food product for children during this period, is in a highly emulsified state, and the milk itself contains a lipolytic factor that takes part in the digestion of fats.
However, the stomach still plays a role in the digestion of fats in adults. It regulates the flow of fat into the intestines and digests proteins, thus releasing fat from the lipoprotein complexes of food.
The main site of fat digestion is the duodenum and parts of the small intestine. Since fats are insoluble in water, and the enzymes that break them down are water-soluble compounds, a necessary condition for the hydrolytic breakdown of fats into their constituent parts is their dispersion(crushing) to form a thin emulsion. Dispersion and emulsification of fat occurs as a result of the action of several factors: bile acids, free higher fatty acids, mono- and diglycerides, and proteins. This is also facilitated by intestinal peristalsis and the constantly formed carbon dioxide, which is released during the interaction of acidic food components coming from the stomach with intestinal carbonates, creating an alkaline environment. The resulting carbon dioxide “gurgles” through the food mass, thus participating in the dispersion of fat. Neutralization of the contents of the stomach is also facilitated by the entry into the lumen of the small intestine of bile, which is alkaline in nature.)
Bile is a viscous liquid of light yellow color with a specific odor and a bitter taste. Bile contains bile acids. bile pigments, hemoglobin breakdown products, cholesterol, lecithin, fats, some enzymes, hormones, etc. Bile promotes peristalsis of the small intestine and has a bacteriostatic effect on its microflora. Toxins are excreted from the body with bile. It is also an activator of lipolytic enzymes and increases the permeability of the intestinal wall.
The main components of bile are bile acids. They are formed in the liver from cholesterol and are found in bile in both free and bound states, as well as in the form of sodium salts. Human bile contains mainly three bile acids. The bulk consists of cholic (3,7,12-trihydroxycholanic) and deoxycholic (3,12-dihydroxycholanic), a small part is lithocholic (3-hydroxycholanic) acids, which are derivatives of cholanic acid :
Cholic acid can also be found in bile in a bound state in the form of paired compounds with glycine and the cysteine derivative taurine - glycocholic and taurocholic acids, respectively:
Sodium salt of glycocholic acid
Sodium salt of taurocholic acid
Due to the presence of bile acids, the surface tension of lipid droplets decreases, which contributes to the formation of a very thin and stable emulsion with a particle diameter of about 0.5 microns. Monoglycerides and higher fatty acids also contribute to the formation of emulsion. Emulsification of fat leads to a colossal increase in the surface area of contact between the lipase and the aqueous solution. Thus, the thinner the fat emulsion, the better and faster they are broken down by lipase. In addition, in the form of a thin emulsion, fats can even be absorbed by the intestinal wall directly without being broken down into their component parts.
In the presence of bile acids, under the action of lipase, hydrolytic breakdown of fats occurs in the lumen of the small intestine. As a result of this, products of partial and complete breakdown of fats are formed - mono- and diglycerides, free higher fatty acids and glycerol:
It also contains part of the undigested fat in the form of a very thin emulsion. All these products are subsequently absorbed by the intestinal wall. In this mixture, triglycerides are about 10 % , mono-
idisaccharides - also 10 % , and the bulk - about 80% - are products of the complete breakdown of fats - glycerol and higher fatty acids
Digestion of phosphoglycerides. The main site of digestion of phosphatides is also the duodenum. Emulsification of these lipids occurs under the influence of the same substances as triglycerides. However, the hydrolytic cleavage of phosphatides is carried out under the action of phospholipases A, B, C and D. Each enzyme acts on a specific ester bond of the phospholipid. Hydrolytic breakdown of, for example, lecithin occurs as follows:
A small part of phosphatides undergoes such complete breakdown, since its intermediate products are highly soluble in water and are easily absorbed by the intestinal wall. In addition, phosphoglycerides easily form emulsions, which can also be absorbed by the intestinal wall.
Digestion of sterides. Steroids included in food are emulsified under the influence of the same factors as fats, after which they undergo hydrolytic breakdown to free sterols and higher fatty acids. This process is carried out under the action of an enzyme cholesterol esterase.
Lipid absorption
As a result of the digestion of fats, phosphatides, sterides in the lumen of the small intestine, a significant amount of products of their partial and complete hydrolytic breakdown is formed: mono- and diglycerides, higher fatty acids, sterols, nitrogenous bases, phosphoric acid. It also contains a small amount of triglycerides, which are in a finely emulsified state. All these products are absorbed by the wall of the small intestine.
Digestion products such as fatty acids and cholesterol, poorly soluble in water, form water-soluble complexes with bile acids - the so-called choleic acids. These acids easily penetrate the epithelial cells of the intestinal wall, where they are broken down into their component parts. The released bile acids return to the intestinal lumen and are again used to transport water-insoluble fat breakdown products.
Some of the breakdown products (glycerol, glycerol phosphoric acid, nitrogenous bases) are highly soluble in water and easily penetrate epithelial cells. Phosphoric acid is absorbed into the epithelial cells of the wall of the small intestine in the form of sodium and potassium salts. The absorption of lipids is based on a number of complex physicochemical and biological processes, the implementation of which requires the energy of macroergic bonds of ATP.
In the epithelial cells of the intestinal mucosa, lipids are again synthesized from the absorbed products of hydrolytic cleavage. However, this resynthesis leads to the formation of specific fats characteristic of a given organism.
To form neutral fats, higher fatty acids, glycerol, mono- and diglycerides are used. At the same time, the synthesis of phosphatides occurs, for which mainly glycerol phosphoric acid, glycerides and diglycerides, as well as small amounts of monoglycerides, are used. Steroids are formed from cholesterol and higher fatty acids.
In the epithelial cells of the intestinal wall, complexes 150-200 nm in size, called Hilo microns. The internal contents of the chylomicron, represented by various types of lipids formed, mainly triglycerides, are surrounded by an outer protein shell, due to which the chylomicrons are highly soluble in water. Chilo-microns diffuse first into the intercellular fluid, then into the lymphatic capillaries and finally enter the bloodstream, where under the influence of heparin they disintegrate into small particles. With the bloodstream, they are carried throughout the body and deposited in reserve in fat depots - subcutaneous and perinephric tissue, omentum, mesentery, and muscle tissue. Some of the blood fats are used for plastic purposes, as a source of chemical energy, etc.
Thus, chylomicrons are carriers of lipids formed in the epithelial cells of the small intestine. At the same time, they transport mainly triglycerides in the blood.
Along with chylomicrons, there are other forms of lipid transport in the blood, for example α- and β-lipoproteins. Their molecules are complex complexes of lipids and proteins. α-Lipoproteins are the main transport forms of phosphatides, β-lipoproteins are carriers of cholesterol and its esters.
The most mobile form of lipids are free higher fatty acids.
An important role in the active transport of lipids belongs to the formed elements of blood. Erythrocytes, for example, are involved in the transport of phosphatides and cholesterol, leukocytes - triglycerides.
A large role in lipid metabolism belongs to fat depots. Studies have shown that not only specific type of fat newly synthesized in the body is deposited in fat depots, but also foreign fat in small quantities, i.e. included in food. Experiments conducted on starving dogs showed that dietary fats, after absorption, first enter fat depots, from which they pass into the blood plasma.
Thus, adipose tissue is not a passive fat depot; its composition is constantly updated due to lipids absorbed from the intestines or synthesized in the body.
Under aerobic conditions, glucose is oxidized to CO 2 and H 2 O. The overall equation is:
C 6 H 12 O 6 + 6O 2 → 6CO 2 + 6H 2 O + 2880 kJ/mol.
This process includes several stages:
Aerobic glycolysis . In it, 1 glucose is oxidized to 2 PVC, with the formation of 2 ATP (first 2 ATP are consumed, then 4 are formed) and 2 NADH 2;
Conversion of 2 PVK into 2 acetyl-CoA with the release of 2 CO 2 and the formation of 2 NADH 2;
CTK. It oxidizes 2 acetyl-CoA with the release of 4 CO 2, the formation of 2 GTP (yielding 2 ATP), 6 NADH 2 and 2 FADH 2;
Oxidative phosphorylation chain. In it, 10 (8) NADH 2, 2 (4) FADH 2 are oxidized with the participation of 6 O 2, while 6 H 2 O is released and 34 (32) ATP is synthesized.
As a result of aerobic oxidation of glucose, 38 (36) ATP is formed, of which: 4 ATP in reactions of substrate phosphorylation, 34 (32) ATP in reactions of oxidative phosphorylation. The efficiency of aerobic oxidation will be 65%.
Anaerobic oxidation of glucose
Glucose catabolism without O2 occurs in anaerobic glycolysis and PFS (PFP).
During anaerobic glycolysis 1 glucose is oxidized to 2 molecules of lactic acid with the formation of 2 ATP (first 2 ATP are consumed, then 4 are formed). Under anaerobic conditions, glycolysis is the only source of energy. The overall equation is: C 6 H 12 O 6 + 2H 3 PO 4 + 2ADP → 2C 3 H 6 O 3 + 2ATP + 2H 2 O.
During PFP Pentoses and NADPH 2 are formed from glucose. During PFS Only NADPH 2 is formed from glucose.
GLYCOLYSIS
Glycolysis is the main pathway for the catabolism of glucose (as well as fructose and galactose). All its reactions take place in the cytosol.
Aerobic glycolysis is the process of oxidation of glucose to PVC, occurring in the presence of O 2.
Anaerobic glycolysis is the process of oxidation of glucose to lactate, occurring in the absence of O 2.
Anaerobic glycolysis differs from aerobic glycolysis only in the presence of the last 11 reactions; the first 10 reactions are common to them.
Stages of glycolysis
In any glycolysis, 2 stages can be distinguished:
Stage 1 is preparatory, it consumes 2 ATP. Glucose is phosphorylated and broken down into 2 phosphotrioses;
Stage 2 is associated with ATP synthesis. At this stage, phosphotrioses are converted to PVC. The energy of this stage is used for the synthesis of 4 ATP and the reduction of 2NADH 2, which under aerobic conditions is used for the synthesis of 6 ATP, and under anaerobic conditions they reduce PVA to lactate.
Energy balance of glycolysis
Thus, the energy balance of aerobic glycolysis is:
8ATP = -2ATP + 4ATP + 6ATP (from 2NADH 2)
Energy balance of anaerobic glycolysis:
2ATP = -2ATP + 4ATP
General reactions of aerobic and anaerobic glycolysis
1. Hexokinase (hexokinase II, ATP: hexose-6-phosphotransferase) in muscles phosphorylates mainly glucose, less fructose and galactose. Km<0,1 ммоль/л. Ингибитор глюкозо-6-ф, АТФ. Активатор адреналин. Индуктор инсулин.
Glucokinase (hexokinase IV, ATP: glucose-6-phosphotransferase) phosphorylates glucose. Km - 10 mmol/l, active in the liver and kidneys. Glucose-6-ph is not inhibited. Insulin inducer. Hexokinases carry out phosphorylation of hexoses.
2. Phosphohexose isomerase (glucose-6ph-fructose-6ph-isomerase) carries out aldo-ketoisomerization of open forms of hexoses.
3. Phosphofructokinase 1 (ATP: fructose-6ph-1-phosphotransferase) carries out phosphorylation of fructose-6ph. The reaction is irreversible and the slowest of all glycolysis reactions, determining the rate of all glycolysis. Activated by: AMP, fructose-2,6-df (a powerful activator, formed with the participation of phosphofructokinase 2 from fructose-6ph), fructose-6-ph, Fn. Inhibited by: glucagon, ATP, NADH 2, citrate, fatty acids, ketone bodies. Inducer of the insulin response.
4. Aldolaza A (fructose-1,6-ph: DAP-lyase). Aldolases act on open forms of hexoses, have 4 subunits, and form several isoforms. Most tissues contain Aldolase A. The liver and kidneys contain Aldolase B.
5. Phosphotriose isomerase (DAP-PHA isomerase).
6. 3-PHA dehydrogenase (3-PHA: NAD+ oxidoreductase (phosphorylating)) consists of 4 subunits. Catalyzes the formation of a high-energy bond in 1,3-PGA and the reduction of NADH 2, which are used under aerobic conditions for the synthesis of 8 (6) ATP molecules.
7. Phosphoglycerate kinase (ATP: 3PGA-1-phosphotransferase). Carries out substrate phosphorylation of ADP to form ATP.
In the following reactions, the low-energy phosphoester is converted to high-energy phosphate.
8. Phosphoglycerate mutase (3-PGA-2-PGA isomerase) transfers the phosphate residue to PGA from position 3 to position 2.
9. Enolase (2-PHA: hydro-lyase) splits off a water molecule from 2-PHA and forms a high-energy bond with phosphorus. Inhibited by F - ions.
10. Pyruvate kinase (ATP: PVK-2 phosphotransferase) carries out substrate phosphorylation of ADP to form ATP. Activated by fructose-1,6-df, glucose. Inhibited by ATP, NADH 2, glucagon, adrenaline, alanine, fatty acids, Acetyl-CoA. Inducer: insulin, fructose.
The resulting enol form of PVK is then non-enzymatically converted to a more thermodynamically stable keto form. This reaction is the last for aerobic glycolysis.
Further catabolism of 2 PVK and the use of 2 NADH 2 depends on the availability of O 2 .
BELARUSIAN STATE UNIVERSITY OF INFORMATICS AND RADIO ELECTRONICS
Department of ETT
« Aerobic oxidation of carbohydrates. Biological oxidation and reduction"
MINSK, 2008
Aerobic oxidation of carbohydrates- the main way of energy production for the body. Indirect - dichotomous and direct - apotomic.
The direct pathway of glucose breakdown is pentose cycle– leads to the formation of pentoses and the accumulation of NADPH 2. The pentose cycle is characterized by the sequential elimination of each of its 6 carbon atoms from glucose molecules with the formation of 1 molecule of carbon dioxide and water during one cycle. The breakdown of the entire glucose molecule occurs over 6 repeating cycles.
The importance of the pentose phosphate cycle of carbohydrate oxidation in metabolism is great:
1. It supplies reduced NADP, necessary for the biosynthesis of fatty acids, cholesterol, etc. Due to the pentose cycle, 50% of the body's need for NADPH 2 is covered.
2. Supply of pentose phosphates for the synthesis of nucleic acids and many coenzymes.
The reactions of the pentose cycle occur in the cytoplasm of the cell.
In a number of pathological conditions, the proportion of the pentose pathway of glucose oxidation increases.
Indirect path– breakdown of glucose to carbon dioxide and water with the formation of 36 molecules of ATP.
1. Breakdown of glucose or glycogen to pyruvic acid
2. Conversion of pyruvic acid to acetyl-CoA
Oxidation of acetyl-CoA in the Krebs cycle to carbon dioxide and water
C 6 H 12 O 6 + 6 O 2 ® 6 CO 2 + 6 H 2 O + 686 kcal
In the case of aerobic conversion, pyruvic acid undergoes oxidative decarboxylation to form acetyl-CoA, which is then oxidized to carbon dioxide and water.
The oxidation of pyruvate to acetyl-CoA is catalyzed by the pyruvate dehydrogenase system and occurs in several stages. Total reaction:
Pyruvate + NADH + NS-CoA ® acetyl-CoA + NADH 2 + CO 2 reaction is almost irreversible
Complete oxidation of acetyl-CoA occurs in the tricarboxylic acid cycle or Krebs cycle. This process takes place in mitochondria.
The cycle consists of 8 consecutive reactions:
In this cycle, a molecule containing 2 carbon atoms (acetic acid in the form of acetyl-CoA) reacts with a molecule of oxaloacetic acid, resulting in the formation of a compound with 6 carbon atoms - citric acid. During the process of dehydrogenation, decarboxylation and preparatory reaction, citric acid is converted back into oxaloacetic acid, which easily combines with another acetyl-CoA molecule.
1) acetyl-CoA + oxaloacetate (SCHUK) ®citric acid
citrate synthase
2) citric acid® isocitric acid
aconitate hydratase
3) isocitric acid + NAD®a-ketoglutaric acid + NADH 2 + CO 2
isocitrate dehydrogenase
4) a-ketoglutaric acid + NS-CoA + NAD®succinylSCoA + NADH 2 + CO 2
5) succinyl-CoA+GDP+Fn®succinic acid+GTP+HS-CoA
succinyl CoA synthetase
6) succinic acid+FAD®fumaric acid+FADN 2
succinate dehydrogenase
7) fumaric acid + H 2 O® L malic acid
fumarate hydratase
8) malate + NAD®oxaloacetate + NADH 2
malate dehydrogenase
In total, when a glucose molecule is broken down in tissues, 36 ATP molecules are synthesized. Undoubtedly, this is an energetically more efficient process than glycolysis.
The Krebs cycle is the common final pathway by which the metabolism of carbohydrates, fatty acids and amino acids is completed. All these substances are included in the Krebs cycle at one stage or another. Next, biological oxidation or tissue respiration occurs, the main feature of which is that it proceeds gradually through numerous enzymatic stages. This process occurs in mitochondria, cellular organelles in which a large number of enzymes are concentrated. The process involves pyridine-dependent dehydrogenases, flavin-dependent dehydrogenases, cytochromes, coenzyme Q - ubiquinone, proteins containing non-heme iron.
The rate of respiration is controlled by the ATP/ADP ratio. The lower this ratio, the more intense respiration occurs, ensuring the production of ATP.
Also, the citric acid cycle is the main source of carbon dioxide in the cell for carboxylation reactions, which begin the synthesis of fatty acids and gluconeogenesis. The same carbon dioxide supplies carbon for urea and some units of the purine and pyrimidine rings.
The relationship between the processes of carbohydrate and nitrogen metabolism is also achieved through intermediate products of the citric acid cycle.
There are several pathways through which citric acid cycle intermediates are incorporated into the process of lipogenesis. The breakdown of citrate leads to the formation of acetyl-CoA, which plays the role of a precursor in the biosynthesis of fatty acids.
Isocitrate and malate provide the formation of NADP, which is consumed in the subsequent reductive stages of fat synthesis.
The role of the key factor determining the conversion of NADH is played by the state of adenine nucleotides. High ADP and low ATP indicate low energy reserves. In this case, NADH is involved in the reactions of the respiratory chain, enhancing the processes of oxidative phosphorylation associated with energy storage. The opposite phenomenon is observed at low ADP content and high ATP content. By limiting the electron transport system, they promote the use of NADH in other reducing reactions such as glutamate synthesis and gluconeogenesis.
Biological oxidation and reduction.
Cellular respiration is the totality of enzymatic processes occurring in each cell, as a result of which molecules of carbohydrates, fatty acids and amino acids are ultimately broken down into carbon dioxide and water, and the released biologically useful energy is stored by the cell and then used. Many enzymes that catalyze these reactions are located in the walls and cristae of mitochondria.
It is known that for all manifestations of life - growth, movement, irritability, self-reproduction - a cell must expend energy. All living cells obtain biologically useful energy through enzymatic reactions in which electrons are transferred from one energy level to another. For most organisms, the final electron acceptor is oxygen, which reacts with electrons and hydrogen ions to form a water molecule. The transfer of electrons to oxygen occurs with the participation of an enzyme system located in mitochondria - the electron transfer system. ATP serves as the “energy currency” of the cell and is used in all metabolic reactions that require energy. Energy-rich molecules do not move freely from one cell to another, but are formed in that place. where they should be used. For example, high-energy ATP bonds, which serve as a source of energy for reactions associated with muscle contraction, are formed in the muscle cells themselves.
The process in which atoms or molecules lose electrons (e -) is called oxidation, and the reverse process - the addition (attachment) of electrons to an atom or molecule - is called reduction.
A simple example of oxidation and reduction is the reversible reaction - Fe 2+ ®Fe 3+ + e -
Reaction going to the right - oxidation, removal of an electron
To the left - reduction (addition of an electron)
All oxidation reactions (in which an electron is removed) must be accompanied by reduction - a reaction in which electrons are captured by some other molecule, because they do not exist in a free state.
The transfer of electrons through the electron transport system occurs through a series of sequential oxidation-reduction reactions, which together are called biological oxidation. If the energy of the electron flow accumulates in the form of high-energy phosphate bonds (~P), then the process is called oxidative phosphorylation. Specific compounds that form an electron transport system and that are alternately oxidized and reduced are called cytochromes. Each of the cytochromes is a protein molecule to which is attached a chemical group called heme; at the center of the heme is an iron atom, which is alternately oxidized and reduced, giving or accepting one electron.
All biological oxidation reactions occur with the participation of enzymes, and each enzyme is strictly specific and catalyzes either the oxidation or the reduction of very specific chemical compounds.
Another component of the electron transfer system, ubiquinone or coenzyme Q, is capable of acquiring or donating electrons.
Mitochondria are contained in the cytoplasm of the cell and are microscopic rod-shaped or other shaped formations, the number of which in one cell amounts to hundreds or thousands.
What are mitochondria, what is their structure? The internal space of mitochondria is surrounded by two continuous membranes, with the outer membrane being smooth and the inner one forming numerous folds or cristae. The intramitochondrial space, bounded by the inner membrane, is filled with the so-called matrix, which is approximately 50% protein and has a very fine structure. Mitochondria contain a large number of enzymes. The outer membrane of mitochondria does not contain any of the components of the respiratory catalyst chain. Based on the enzyme composition of the outer membrane, it is still difficult to answer the question of what its purpose is. Perhaps it plays the role of a partition separating the internal, working part of the mitochondria from the rest of the cell. Enzymes of the respiratory chain are associated with the inner membrane. The matrix contains a number of Krebs cycle enzymes.
Aerobic oxidation of carbohydrates is the main way of energy production for the body. Indirect - dichotomous and direct - apotomic.
The direct pathway of glucose breakdown is pentose cycle- leads to the formation of pentoses and the accumulation of NADPH 2. The pentose cycle is characterized by the sequential elimination of each of its 6 carbon atoms from glucose molecules with the formation of 1 molecule of carbon dioxide and water during one cycle. The breakdown of the entire glucose molecule occurs over 6 repeating cycles.
The importance of the pentose phosphate cycle of carbohydrate oxidation in metabolism is great:
1. It supplies reduced NADP, necessary for the biosynthesis of fatty acids, cholesterol, etc. Due to the pentose cycle, 50% of the body's need for NADPH 2 is covered.
2. Supply of pentose phosphates for the synthesis of nucleic acids and many coenzymes.
The reactions of the pentose cycle occur in the cytoplasm of the cell.
In a number of pathological conditions, the proportion of the pentose pathway of glucose oxidation increases.
Indirect path- breakdown of glucose to carbon dioxide and water with the formation of 36 molecules of ATP.
1. Breakdown of glucose or glycogen to pyruvic acid
2. Conversion of pyruvic acid to acetyl-CoA
Oxidation of acetyl-CoA in the Krebs cycle to carbon dioxide and water
C 6 H 12 O 6 + 6 O 2 6 CO 2 + 6 H 2 O + 686 kcal
In the case of aerobic conversion, pyruvic acid undergoes oxidative decarboxylation to form acetyl-CoA, which is then oxidized to carbon dioxide and water.
The oxidation of pyruvate to acetyl-CoA is catalyzed by the pyruvate dehydrogenase system and occurs in several stages. Total reaction:
Pyruvate + NADH + NS-CoA acetyl-CoA + NADH 2 + CO 2 reaction is almost irreversible
Complete oxidation of acetyl-CoA occurs in the tricarboxylic acid cycle or Krebs cycle. This process takes place in mitochondria.
The cycle consists of 8 consecutive reactions:
In this cycle, a molecule containing 2 carbon atoms (acetic acid in the form of acetyl-CoA) reacts with a molecule of oxaloacetic acid, resulting in the formation of a compound with 6 carbon atoms - citric acid. During the process of dehydrogenation, decarboxylation and preparatory reaction, citric acid is converted back into oxaloacetic acid, which easily combines with another acetyl-CoA molecule.
1) acetyl-CoA + oxaloacetate (OA) citric acid
citrate synthase
2) citric acid isocitric acid
aconitate hydratase
3) isocitric acid + NAD-ketoglutaric acid + NADH 2 + CO 2
isocitrate dehydrogenase
4)-ketoglutaric acid + NS-CoA + NADsuccinylSCoA + NADH 2 + CO 2
5) succinyl-CoA+GDP+Fsuccinic acid+GTP+HS-CoA
succinyl CoA synthetase
6) succinic acid + FADfumaric acid + FADN 2
succinate dehydrogenase
7) fumaric acid + H 2 O L malic acid
fumarate hydratase
8) malate + NADoxaloacetate + NADH 2
malate dehydrogenase
In total, when a glucose molecule is broken down in tissues, 36 ATP molecules are synthesized. Undoubtedly, this is an energetically more efficient process than glycolysis.
The Krebs cycle is the common final pathway by which the metabolism of carbohydrates, fatty acids and amino acids is completed. All these substances are included in the Krebs cycle at one stage or another. Next, biological oxidation or tissue respiration occurs, the main feature of which is that it proceeds gradually through numerous enzymatic stages. This process occurs in mitochondria, cellular organelles in which a large number of enzymes are concentrated. The process involves pyridine-dependent dehydrogenases, flavin-dependent dehydrogenases, cytochromes, coenzyme Q - ubiquinone, proteins containing non-heme iron.
The rate of respiration is controlled by the ATP/ADP ratio. The lower this ratio, the more intense respiration occurs, ensuring the production of ATP.
Also, the citric acid cycle is the main source of carbon dioxide in the cell for carboxylation reactions, which begin the synthesis of fatty acids and gluconeogenesis. The same carbon dioxide supplies carbon for urea and some units of the purine and pyrimidine rings.
The relationship between the processes of carbohydrate and nitrogen metabolism is also achieved through intermediate products of the citric acid cycle.
There are several pathways through which citric acid cycle intermediates are incorporated into the process of lipogenesis. The breakdown of citrate leads to the formation of acetyl-CoA, which plays the role of a precursor in the biosynthesis of fatty acids.
Isocitrate and malate provide the formation of NADP, which is consumed in the subsequent reductive stages of fat synthesis.
The role of the key factor determining the conversion of NADH is played by the state of adenine nucleotides. High ADP and low ATP indicate low energy reserves. In this case, NADH is involved in the reactions of the respiratory chain, enhancing the processes of oxidative phosphorylation associated with energy storage. The opposite phenomenon is observed at low ADP content and high ATP content. By limiting the electron transport system, they promote the use of NADH in other reducing reactions such as glutamate synthesis and gluconeogenesis.
At the first stage, glucose is split into 2 trioses:
Thus, at the first stage of glycolysis, 2 molecules of ATP are spent on activating glucose and 2 molecules of 3-phosphoglyceraldehyde are formed.
In the second stage, 2 molecules of 3-phosphoglyceraldehyde are oxidized to two molecules of lactic acid.
The significance of the lactate dehydrogenase reaction (LDH) is to oxidize NADH 2 to NAD under oxygen-free conditions and allow the glycerophosphate dehydrogenase reaction to occur.
The overall equation of glycolysis: glucose + 2ADP + 2H 3 PO 4 → 2 lactate + 2ATP + 2H 2 O
Glycolysis occurs in the cytosol. Its regulation is carried out by key enzymes - hexokinase, phosphofructokinase And pyruvate kinase. These enzymes are activated by ADP and NAD and inhibited by ATP and NADH 2 .
The energy efficiency of anaerobic glycolysis comes down to the difference between the number of ATP molecules consumed and the number of ATP molecules produced. 2 ATP molecules are consumed per glucose molecule in the hexokinase reaction and the phosphofructokinase reaction. 2 molecules of ATP are formed per molecule of triose (1/2 glucose) in the glycerokinase reaction and pyruvate kinase reaction. For a molecule of glucose (2 trioses), 4 molecules of ATP are formed, respectively. Total balance: 4 ATP – 2 ATP = 2 ATP. 2 ATP molecules accumulate ≈ 20 kcal, which is about 3% of the energy of complete oxidation of glucose (686 kcal).
Despite the relatively low energy efficiency of anaerobic glycolysis, it has an important biological significance in that it the only one a method of generating energy in oxygen-free conditions. In conditions of oxygen deficiency, it ensures the performance of intense muscle work and the beginning of muscle work.
In children anaerobic glycolysis is very active in fetal tissues under conditions of oxygen deficiency. It remains active during the neonatal period, gradually giving way to aerobic oxidation.
Further conversion of lactic acid.
- With an intensive supply of oxygen under aerobic conditions, lactic acid is converted into PVA and, through acetyl CoA, is included in the Krebs cycle, providing energy.
- Lactic acid is transported from muscles to the liver, where it is used for glucose synthesis - the Cori cycle.
Measles cycle
- At high concentrations of lactic acid in tissues, it can be excreted through the kidneys to prevent acidosis.