General scheme of nutrient catabolism in the body. Phases of catabolism, energy effect of individual phases
Metabolism and energy - a set of processes of transformation of substances and energy in living organisms and the exchange of substances and energy between the body and the environment. Metabolism includes 3 stages - the intake of substances into the body, metabolism, or intermediate metabolism, and the release of final metabolic products.
The main functions of metabolism are to extract energy from environment(in the form of chemical energy of organic substances), transformation of exogenous substances into building blocks, assembly of proteins, nucleic acids, fats from building blocks, synthesis and destruction of those biomolecules that are necessary to perform various specific functions of a given cell.
There are two sides of metabolism - anabolism and catabolism
Catabolism is the enzymatic breakdown of high-molecular compounds to their constituent monomers and the further breakdown of monomers to the final products: carbon dioxide, ammonia, lactate.
The main reactions of catabolism are oxidation reactions that supply energy to the cell. Energy can be stored in two forms: ATP, NADPH + H - a hydrogen donor in reduction reactions during the synthesis of a number of compounds.
Anabolism is the enzymatic synthesis of the main macromolecules of the cell, as well as the formation of biological active compounds, requires the expenditure of free energy (ATP, NADPH + H).
Differences between catabolism and anabolism. Catabolism - breakdown, storage of ATP. Anabolism is the synthesis but consumption of ATP. The paths are not the same, the number of reactions is different. They differ in localization. Different genetic and allosteric regulation.
The main energy source for humans is the energy stored in chemical bonds food products. Ratio B:F:U = 1:1:4. A person receives 55% of energy from carbohydrates, 15% from proteins, 30% from fats (80% comes from animal fats, and 20% from vegetable fats).
The daily human need for energy is 3000 kcal. A person’s daily need for energy depends on: work (during hard physical work, the basal metabolic rate is higher), gender (in women, the metabolic rate is 6-10% lower), temperature (with an increase in body temperature by one degree, the metabolic rate increases by 13%), age (with age, starting from 5 years, the basal metabolic rate decreases).
About 60 kg of ATP is formed and broken down in the body per day. The ATP-ADP cycle is constantly working. It involves the use of ATP for various types of work and the regeneration of ATP through catabolic reactions.
Unification nutrients goes in three phases.
I. Preparatory phase. High molecular weight compounds decompose under the action of gastrointestinal hydrolases to monomers. Occurs in the gastrointestinal tract and lysosomes. Not an energy supplier (1%).
Phase II. Conversion of monomers into simple compounds - central metabolites (PVC, acetyl CoA). These products connect 3 types of metabolism, up to 2-3 s, proceeds in the cytoplasm, ends in the mitochondria, provides 20-30% of the energy supplied anaerobically.
Phase III. Krebs cycle. Aerobic conditions, complete oxidation of substances supplied with food, release a large amount of energy and accumulate it in ATP.
Anabolic pathways diverge
1st phase. Protein synthesis begins with the formation of α-keto acids.
Phase 2. Amination of α-keto acids, obtaining AMK.
Phase 3. Proteins are formed from AMK. 2 CO2
General path of catabolism. After the formation of PVC, the further decomposition of substances to carbon dioxide and water occurs in the same way in the general catabolic pathway (CCP). OPC includes the oxidative decarboxylation reactions of PVA and TCA cycle. OPC reactions occur in the mitochondrial matrix and reduced coenzymes transfer hydrogen to components of the respiratory chain. The catabolic pathways converge, merging into the TCA cycle in the third phase.
In the first phase, proteins produce 20 AMK. In the second phase, 20 AMKs produce acetyl CoA and ammonia. In the third phase, the TCA produces carbon dioxide, water and energy.
Metabolic pathways are a set of enzyme-catalyzed reactions during which a substrate is converted into a product. The main (main) metabolic pathways are universal, characteristic of any cell. They supply energy, synthesis of the main biopolymers of the cell. Accessory pathways are less universal and are characteristic of certain tissues and organs. Synthesis of important substances. They supply energy in the form of NADPH+H.
Cycle tricarboxylic acids discovered in 1937 by G. Krebs, it occurs in a cyclic mode in the mitochondrial matrix, in each revolution of the TCA cycle one acetyl group, 2 carbon atoms enter in the form of acetyl CoA, and with each revolution 2 molecules of carbon dioxide are removed from the cycle. Oxaloacetate is not consumed in the TCA cycle, as it regenerates.
Citrate isomerization - α-Ketoglutarate is oxidized to succinyl CoA and carbon dioxide.
The TCA cycle is a specific mechanism for the breakdown of acetylCoA into 2 types of products: carbon dioxide - a product of complete oxidation, reduced nucleotides, the oxidation of which is the main source of energy.
When one molecule of acetylCoA is oxidized in the TCA cycle and the oxidative phosphorylation system, 12 ATP molecules are formed: 1ATP due to substrate phosphorylation, 11ATP due to oxidative phosphorylation. Oxidation energy is accumulated in the form of reduced nucleotides and 1ATP. The gross equation of the TCA cycle is AcetylCoA + 3NAD + FAD+ ADP+Pn+2H20→ 2CO2+ 3NAD+H + FADH2+ ATP + CoASH
The TCA cycle is the central metabolic pathway. Functions of the TCC: integrating, energy-generating, anabolic.
The relationship of metabolism at the level of the Krebs cycle.
Anabolic function of the TCA cycle. Metabolites of the Krebs cycle are used for the synthesis of various substances: carbon dioxide in carboxylation reactions, α-ketoglutarate → glu, oxaloacetate → glucose, succinate → heme.
The TCA cycle plays a role in the processes of gluconeogenesis, transamination, deamination, and lipogenesis.
Regulation of the TCA cycle. Regulatory enzymes: citrate synthase, isocitrate DH, α-ketoglutarate DH complex.
Positive allosteric effectors of citrate synthase are PIKE, acetylCoA, NAD, ADP.
Negative allosteric effectors of citrate synthase are ATP, citrate, NADH + H, fatty acids, an increase in succinylCoA concentration above normal.
The action of ATP is to increase Km for acetylCoA. As the ATP concentration increases, the saturation of the acetylCoA enzyme decreases and, as a result, the formation of citrate decreases.
Positive allosteric effectors of isocitrate DH are ADP, NAD.
Negative allosteric effectors of isocitrate DH are ATP, NADH + H.
The Krebs cycle is regulated by feedback: ATP is inhibited, ADP is activated. Hypoenergetic states are conditions in which ATP synthesis decreases.
Tissue hypoxia due to: decreased oxygen concentration in the air, disruption of cardiovascular and respiratory systems, anemia, hypovitaminosis, fasting.
The role of vitamins in the Krebs cycle - riboflavin (FAD) - coenzyme of SDH, α-ketoglutarate of the DG complex, PP (NAD) - coenzyme of MDH, IDH, α-ketoglutarate of DG, thiamine (TPF) - coenzyme of α-ketoglutarate of the DG complex, pantothenic acid(CoA): acetylCoA, succinylCoA.
Metabolism or metabolism is the sum of targeted reactions occurring under the influence of cell enzyme systems, which are regulated by various external and internal factors, and ensuring the exchange of substances and energy between the environment and the cell.
The entire set of chemical reactions in the cell (metabolism) obeys the principle of biochemical unity– Biochemically, all living beings on Earth are similar. They have uniform building blocks, a common “energy currency” (ATP), a universal genetic code, and fundamentally identical major metabolic pathways.
Reactions leading to the breakdown and oxidation of substances to produce energy are called catabolism; pathways leading to the synthesis of basic complex substances are called anabolism. Catabolism and anabolism are two independent pathways in metabolism, although some parts of them may be common. Such common areas characteristic of catabolism and anabolism are called amphibolic.
Catabolic and anabolic transformations are carried out sequentially, since the reaction product of the previous stage is the substrate for the next one.
Energy exchange is closely related to constructive (Fig. 2.1).
During biological oxidation, various intermediate products are formed (phosphoric esters of sugars, pyruvic, acetic, oxaloacetic, succinic, a-ketoglutaric acids), from which monopolymers (amino acids, nitrogenous bases, monosaccharides) are first synthesized, and then the main macromolecules of the cell. The synthesis of cell components occurs with the expenditure of energy, which is generated during energy metabolism. This energy is also spent on the active transport of substances necessary for anabolism.
The relationship between constructive and energy metabolism lies in the fact that biosynthesis processes, in addition to energy, require the supply of a reducing agent in the form of hydrogen from the outside, the source of which is also energy exchange reactions.
The rate of reactions and the cell’s metabolism in general depend on the composition of the nutrient medium, the conditions for cultivating microorganisms and, most importantly, on the cell’s need at any given moment for energy (ATP) and biosynthetic structures. The cell releases energy very economically, and synthesizes exactly as much substances as it needs at the moment. This principle underlies the regulation and control of all stages of metabolic pathways in the cell.
The regulation of metabolism in a microbial cell has a complex interdependent system that “turns on” and “turns off” certain enzymes using a variety of factors: pH of the environment, concentration of substrates, some intermediate and final metabolites, etc. Studying the ways of regulation of certain metabolic products in the cell opens up unlimited possibilities for determining the optimal conditions for the biosynthesis of target products by microorganisms.
enzymes for further transformations
hydrolysis productsA
B
Fig.2.1. Scheme of catabolism and anabolism of a microbial cell
A – constructive exchange; B – energy metabolism
For the existence of life, both the regulation of the activity of individual metabolic pathways and the coordination of the activities of these pathways are important.
Each of the many substances is created in the cell in proportions strictly necessary for growth as a result of enzymatic reactions. Enzymes that are constantly synthesized in the cell and the formation of which does not depend on the composition of the nutrient medium are called constitutive, for example, glycolytic enzymes . Other enzymes adaptive or inducible, arise only in response to the appearance of inducers in the nutrient medium - substrates or their structural analogues.
The coordination of chemical transformations, ensuring the economy of metabolism, is carried out in microorganisms by three main mechanisms:
· regulation of enzyme activity, including through retroinhibition;
· regulation of the volume of enzyme synthesis (induction and repression of enzyme biosynthesis);
· catabolite repression.
In progress retroinhibition (feedback inhibition) the activity of the enzyme (allosteric protein), which is at the beginning of the multi-stage transformation of the substrate, is inhibited by the final metabolite, for example:
Aspartate →Carbamyl aspartate →Dihydro-orotic acid →Orotic acid →
→ Orotidine monophosphate → UMP → CTP
Carbamyltransferase
Chorismate → Anthranilate → Indolyl glycerophosphate → Tryptophan
Anthranilate synthetase
Low molecular weight metabolites convey information about their concentration levels and metabolic status to key metabolic enzymes. Key enzymes are regulators of the frequency of product formation. Using the described mechanism, the final products self-regulate their biosynthesis. Retroinhibition is a way to precisely and quickly regulate product formation. Metabolism similar to that of the final metabolites is affected by their analogues.
Regulation of the volume of enzyme biosynthesis (induction and repression) carried out at the operon level (F. Jacob and J. Monod, 1961) by changing the amount of mRNA produced during transcription.
A bacterial cell has many genes, each of which carries information and controls the synthesis of one protein or corresponding compound. Genes are subdivided into structural genes, regulatory genes and operator genes. IN structural genes information about the primary structure of the protein they control is encoded, i.e. about the sequence of arrangement of amino acids that make up the protein. Gene regulators control the synthesis of repressor proteins that suppress the function of structural genes, and operator genes act as intermediaries between regulatory genes and structural genes. (Fig. 2.2).
which in turn is capable of occupying the initial binding zone of RNA polymerase (operator), thereby preventing the latter from binding to the promoter region and the start of mRNA synthesis. The end products of metabolic pathways can not only inhibit the activity of enzymes in the first stages of the process, but also inhibit the biosynthesis of enzymes in its last stages, activating the repressor protein.
The discovered phenomenon is named repression, and enzymes whose biosynthesis is inhibited under the influence of low molecular weight metabolites that convert the repressor protein into active form, are called repressive. These include glutamine synthetase, tryptophan synthetase, ornithine carbamyltransferase, urease, etc. If the concentration of the final product decreases to a certain very low level, then derepression of the enzyme occurs, i.e., the rate of their biosynthesis increases to the required values.
In progress induction a low-molecular-weight metabolite-inducer (for example, lactose), combining with a repressor protein (product of a gene-regulator), inactivates it and thereby prevents the interaction of the repressor protein with the operator zone, which makes it possible for RNA polymerase to attach to the promoter and begin mRNA synthesis. Bacterial cells produce a variety of low-molecular effectors in response to environmental changes (stress, starvation, the action of phages, etc.). Each of the effectors, interacting through an allosteric mechanism with certain regulatory proteins, models the promoter specificity of RNA polymerase, thereby triggering the expression of a certain set of genes.
Catabolite repression. The essence of catabolite repression is the suppression of the biosynthesis of enzymes that ensure the metabolism of one carbon source by another carbon source. Previously, it was believed that the reason for such repression was the suppression of the biosynthesis of metabolic enzymes of one carbon source by the catabolic products of another.
If several different carbon sources are present in the nutrient medium, the microorganism cell produces enzymes for the assimilation of only one, the most preferred substrate. For example, when cells are grown on a mixture of glucose and lactose, glucose is utilized first. After complete utilization of glucose, expression of lactose metabolic enzymes occurs (expression of structural genes of the lactose operon). The lactose operon (lac operon) includes the structural genes of three enzymes: X, Y and A (responsible for the interdependent synthesis of β-galactosidase, galactosylpermease and acetyltransferase), which control the metabolism of lactose in the cell. The absence of glucose in the medium is signaled by cAMP, the synthesis of which is suppressed in the presence of glucose. The level of cAMP in the cell is a function of adenylate cyclase activity. cAMP is a necessary component for the binding of RNA polymerase to the promoter region and the initiation of transcription of genes responsible for the synthesis of these enzymes. In the presence of glucose, the concentration of cAMP is insufficient to form a complex.
So, the task of regulatory mechanisms is to effectively regulate and coordinate metabolic pathways in order to maintain the required concentration of cellular components. In addition, cells must adequately respond to changes in environmental conditions by incorporating new catabolic pathways aimed at using currently available nutritional substrates. Regulation is important for maintaining the balance between energy and synthetic reactions in the cell.
QUESTIONS FOR SELF-CHECK:
1. What is the essence of energy metabolism?
2. What is the relationship between constructive and energy exchange?
3. What is “phosphorylation”?
4. What enzymes take part in the energy metabolism of aerobes, facultative anaerobes, and obligate anaerobes?
5. What is meant by “amphibolic pathways”?
6. Enzymes and their biochemical role.
7. Classification and nomenclature of enzymes.
8. Active sites of enzymes. Substrate specificity.
9. Factors providing enzymatic catalysis.
10. Describe the equilibrium state of an enzymatic reaction?
11. Why do enzymes speed up reactions? What is activation energy?
12. What determines the speed of an enzymatic reaction?
13. What is enzyme specificity?
14. What are the names of enzymes that are released into the external environment?
15. What are inducible enzymes?
16. What are constitutive enzymes?
17. What are coenzymes? Name their classes.
18. What are the names of enzymes that catalyze synthetic processes?
19. What is retroinhibition?
20. The essence of the theory of regulation of enzyme synthesis by F. Jacob and J. Monod.
21. Explain the mechanism of induction of enzyme synthesis.
22. Explain the mechanism of repression of enzyme synthesis.
23. What is catabolite repression?
Vitamin C (ascorbic acid). Structure, daily requirement, food sources, vitamin deficiency. Participation in redox processes, steroidogenesis and collagen formation. Hydroxylation reactions of proline and lysine.
Ascorbic acid is a lactone of an acid similar in structure to glucose. It exists in two forms: reduced (AA) and oxidized (dehydroascorbic acid, DAC).
Both of these forms of ascorbic acid quickly and reversibly transform into each other and, as coenzymes, participate in redox reactions. Ascorbic acid can be oxidized by atmospheric oxygen, peroxide and other oxidizing agents. DAK is easily reduced by cysteine, glutathione, and hydrogen sulfide. In a slightly alkaline environment, the lactone ring is destroyed and biological activity is lost. When food is cooked in the presence of oxidizing agents, some of the vitamin C is destroyed.
Sources vitamin C - fresh fruits, vegetables, herbs, rose hips, sea buckthorn, black currants, lemons, oranges, apples.
Daily requirement human vitamin C is 50-75 mg.
Biological functions. The main property of ascorbic acid is its ability to easily oxidize and reduce. Together with DAK, it forms a redox couple in cells with a redox potential of +0.139 V. Thanks to this ability, ascorbic acid is involved in many hydroxylation reactions: Pro and Lys residues in the synthesis of collagen (the main protein of connective tissue), in the hydroxylation of dopamine, in the synthesis of steroids hormones in the adrenal cortex
In the intestine, ascorbic acid reduces Fe 3+ to Fe 2+, promoting its absorption, accelerates the release of iron from ferritin, and promotes the conversion of folate into coenzyme forms. Ascorbic acid is classified as a natural antioxidant (see section 8). Great value The famous American scientist L. Pauling, a two-time Nobel Prize laureate, attributed this role to vitamin C. He recommended using large doses of ascorbic acid (2-3 g) for the prevention and treatment of a number of diseases (for example, colds).
Clinical manifestations of vitamin C deficiency. Deficiency of ascorbic acid leads to a disease called scurvy (scorbut). Scurvy, which occurs in humans when there is insufficient content of fresh fruits and vegetables in the diet, was described more than 300 years ago, from the time of long sea voyages and northern expeditions. This disease is associated with a lack of vitamin C in food. Only humans, primates and guinea pigs suffer from scurvy. The main manifestations of vitamin deficiency are caused mainly by impaired collagen formation in connective tissue. As a result, loosening of the gums, loosening of teeth, and disruption of the integrity of capillaries (accompanied by subcutaneous hemorrhages) are observed. Swelling, joint pain, and anemia occur. Anemia due to scurvy may be associated with impaired ability to use iron stores, as well as with disorders of folic acid metabolism.
18 Question
The relationship between metabolism and energy. Exergonic and endergonic reactions in the cell. Types of high-energy compounds (phosphate, thiosulfate). Structure of ATP, ATP/ADP cycle. Stages of unification of energy substrates in the body: products, energy value. Critical periods of child development and characteristics of their metabolism.
As stated, metabolism in the human body does not proceed chaotically; it is integrated and finely tuned. All transformations of organic substances, the processes of anabolism and catabolism are closely related to each other. In particular, the processes of synthesis and breakdown are interconnected, coordinated and regulated by neurohormonal mechanisms that give chemical processes the desired direction. In the human body, as in living nature in general, there is no independent metabolism of proteins, fats, carbohydrates and nucleic acids. All transformations are combined into a holistic process of metabolism. Currently, the existence of four main stages in the breakdown of carbohydrate and protein-fat molecules, which integrate the formation of energy from main food sources, has been experimentally substantiated. At stage I, polysaccharides are broken down into monosaccharides (usually hexoses); fats are broken down into glycerol and higher fatty acids, and proteins are broken down into their constituent free amino acids. It should be emphasized that these processes are mainly hydrolytic, therefore the small amount of energy released is almost entirely used by organisms as heat.
At stage II, monomeric molecules (hexoses, glycerol, fatty acids and amino acids) undergo further decomposition, during which energy-rich phosphate compounds and acetyl-CoA are formed. In particular, glycolise hexoses are broken down to pyruvic acid and further to acetyl-CoA. This process is accompanied by the formation of a limited number of energy-rich phosphate bonds through substrate phosphorylation. At this stage, higher fatty acids are similarly broken down to acetyl-CoA, while glycerol is oxidized through the glycolytic pathway to pyruvic acid and further to acetyl-CoA. For amino acids, the situation at stage II is somewhat different. With the predominant use of amino acids as an energy source (with carbohydrate deficiency or diabetes mellitus), some of them are directly converted into metabolites of the citric acid cycle (glutamate, aspartate), others indirectly through glutamate (proline, histidine, arginine), others into pyruvate and then into acetyl-CoA (alanine , serine, glycine, cysteine). Finally, a number of amino acids, in particular leucine, isoleucine, are cleaved to acetyl-CoA, and from phenylalanine-tyrosine, in addition to acetyl-CoA, oxaloacetate is formed through fumaric acid. As you can see, stage II can be called the stage of formation of acetyl-CoA, which is essentially a single (common) intermediate product of the catabolism of basic nutritional substances in cells.
At stage III, acetyl-CoA (and some other metabolites, for example α-ketoglutarate, oxaloacetate) undergo oxidation (“combustion”) in the Krebs cycle of di- and tricarboxylic acids. Oxidation is accompanied by the formation of reduced forms of NADH + H+ and FADH2.
At stage IV, electrons are transferred from reduced nucleotides to oxygen (through the respiratory chain). It is accompanied by the formation of the final product – water molecules. This electron transport is associated with ATP synthesis in the process of oxidative phosphorylation. 3. Endergonic and exergonic reactions
The direction of a chemical reaction is determined by the value of AG. If this value is negative
If it is true, the reaction proceeds spontaneously and is accompanied by a decrease in free energy. Such reactions are called exergonic. If the absolute value of AG is large, then the reaction proceeds almost to completion, and it can be considered irreversible.
If AG is positive, then the reaction will occur only when free energy is supplied from the outside; such reactions are called endergonic.
If the absolute value of AG is large, then the system is stable, and in this case the reaction practically does not occur. When AG equals zero, the system is in equilibrium (Table 6-1).
4. Conjugation of exergonic
and endergonic processes in the body
In biological systems, thermodynamically unfavorable (endergonic) reactions can occur only at the expense of the energy of exergonic reactions. Such reactions are called energetically coupled. Many of these reactions occur with the participation of adenosine tri-
phosphate (ATP), which plays the role of a coupling factor.
Let us consider in more detail the energetics of coupled reactions using the example of glucose phosphorylation.
The reaction of phosphorylation of glucose with free phosphate to form glucose-6-phosphate is endergonic:
(1) Glucose + H3PO4 → Glucose-6-phosphate + H2O (ΔG = +13.8 kJ/mol).
For such a reaction to occur towards the formation of glucose-6-phosphate, it must be coupled with another reaction, the free energy of which is greater than that required for the phosphorylation of glucose.
(2) ATP → ADP + H3PO4 (ΔG = -30.5 kJ/mol).
When processes (1) and (2) are coupled in a reaction catalyzed by hexokinase (see Section 7), glucose phosphorylation easily occurs under physiological conditions; reaction equilibrium
strongly shifted to the right, and it is almost irreversible:
(3) Glucose + ATP → Glucose-6-phosphate + ADP (ΔG = -16.7 kJ/mol).
High-energy compounds are organic compounds of living cells containing energy-rich or high-energy bonds. These compounds are formed as a result of photo- and chemosynthesis and biological oxidation. These include, for example, substances whose hydrolysis releases 2-4 times more energy than the hydrolysis of other substances. High-energy compounds include adenosine triphosphoric acid (ATP), adenosine diphosphoric acid (ADP), as well as pyrophosphate (H4P2O7), polyphosphates (polymers of metaphosphoric acid - (HPO3)n * H2O) and a number of other compounds. The most important high-energy compound is ATP. Using the energy contained in the high-energy bonds of ATP, through the action of enzymes that transfer phosphate groups, it is possible to obtain other high-energy compounds, for example, GTP (guanosine triphosphoric acid), PEP (phosphoenolpyruvic acid), etc. ATP is formed in the processes of biological oxidation and during photosynthesis. Adenosine triphosphoric acid (ATP) is a nucleotide formed by adenosine and three phosphoric acid residues. In all living organisms it acts as a universal battery and energy carrier. Under the action of special enzymes, terminal phosphate groups are cleaved off, releasing energy that goes into synthetic and other life processes.
Adenosine diphosphate (ADP) is a nucleotide formed by adenosone and two phosphoric acid residues. Participates in the energy metabolism of living organisms. ADP obtains energy by dephosphorylation of phosphoenolpyruvic acid under the action of the enzyme transphosphorylase, which transfers the high-energy bond from the acid to ADP. Uridine diphosphoric acid (UDP) and its derivatives take part in the interconversion of carbohydrates. The biosynthesis of the glycosidic bond uses uridine diphosphate glucose (UDPG), which is formed from glucose-1-phosphate and uridine triphosphate (UIP). If UDPG transfers glucose to fructose, then sucrose is formed, and if it is a dextrin chain, a polysaccharide is formed. Glycosides, glycoproteins, etc. are formed in a similar way. The interconversion of monosaccharides occurs through phosphorus esters of sugars or their uridine diphosphate derivatives (UDP derivatives). UDP derivatives of sugars are one or another sugar connected through two phosphoric acid residues to uridine.
Sugar phosphates are a source of phosphorus nutrition for plants. There may be salts of ortho-, meta- and pyrophosphoric acid and organic phosphates. The best of them are water-soluble potassium, sodium, ammonium, calcium and magnesium salts of phosphoric acid.
The energy of macroergic bonds is used to perform any work: activation of compounds (for example, glucose, so that a chain of its oxidative transformations can begin), synthesis of biopolymers (nucleic acids, proteins, polysaccharides), selective absorption of substances from the environment surrounding the cell and release of unnecessary products from the cell, muscle contraction and restoration of the active state of the body, etc. The supply of these compounds allows the body to quickly respond to changes in external conditions and perform physical work.
ATP/ADP cycle.
ATP is an energy-rich molecule because it contains two phosphoanhydride bonds (β, γ). Upon hydrolysis of the terminal phosphoanhydride bond, ATP is converted into ADP and orthophosphate Pi. In this case, the change in free energy is -7.3 kcal/mol. Under normal conditions in the cell (pH 7.0, temperature 37 °C), the actual value of ΔG0" for the hydrolysis process is about -12 kcal/mol. The free energy of ATP hydrolysis makes it possible for it to be formed from ADP due to the transfer of phosphate residue from high-energy phosphates such as phosphoenolpyruvate
Rice. 6-2. Adenosine triphosphoric acid (ATP). There are two high-energy (macroergic) bonds β and γ in the ATP molecule; they are indicated in the figure by the sign ~ (tilde).
or 1,3-bisphosphoglycerate; in turn, ATP can participate in endergonic reactions such as phosphorylation of glucose or glycerol. ATP acts as an energy donor in endergonic reactions of many anabolic processes. Some biosynthetic reactions in the body can occur with the participation of other nucleoside triphosphates, analogues of ATP; these include guanosine triphosphate (GTP), uridine triphosphate (UTP) and cytidine triphosphate (CTP). All these nucleotides, in turn, are formed by using the free energy of the terminal phosphate group of ATP. Finally, due to the free energy of ATP, various types work that underlies the vital functions of the body, for example, such as muscle contraction or active transport of substances.
Thus, ATP is the main, directly used donor of free energy in biological systems. In a cell, an ATP molecule is consumed within one minute after its formation. In humans, an amount of ATP equal to body weight is produced and destroyed every 24 hours.
The use of ATP as an energy source is possible only under the condition of continuous synthesis of ATP from ADP due to the energy of oxidation of organic compounds (Fig. 6-3). The ATP-ADP cycle is the main mechanism of energy exchange in biological systems, and ATP is the universal "energy currency".
Unification of energy substrates in the cell The main substrates of biooxidation are carbohydrates, fats and proteins, which are very different in composition. Phylogenetically, the animal body has developed a system of gradual unification (or standardization) of energy substrates, increasing the efficiency of oxidation. Conventionally, we can distinguish two stages in the unification of energy “fuel” in cells. At stage I (digestion in gastrointestinal tract or breakdown in cells), biopolymers split into their structural components - monomers, losing their original specificity of structure. At stage II (tissue metabolism), monomers are mainly converted into pyruvic acid and/or further into the active form of acetic acid - acetyl-CoA, which is a universal energy substrate. Then, in the Krebs cycle of tricarboxylic acids, oxidation (dehydrogenation) of acetyl-CoA occurs with the formation of reduced coenzymes NAD-H and FAD-H2. In mitochondrial membranes, they are included in the respiratory chain, where, during oxidative phosphorylation in the presence of oxygen, ATP is synthesized from ADP and phosphate. At stages I and II of unification of oxidation substrates, up to 40% is released, and subsequently - about 60% of energy. In this regard, it is the tricarboxylic acid cycle that is considered the main “energy boiler” of the cell. When one gram of carbohydrates and proteins is completely oxidized to CO2 and H2O, about 4.1 kcal is formed, and fat - 9.3 kcal of energy.
In living organisms that are in constant contact and exchange with the environment, continuous chemical changes occur that make up their metabolism (many enzymatic reactions). The scale and direction of metabolic processes are very diverse. Examples:
a) the number of E. coli cells in a bacterial culture can double by 2/3 in 20 minutes in a simple medium with glucose and inorganic salts. These components are absorbed, but only a few are released into the environment by the growing bacterial cell, and it consists of approximately 2.5 thousand proteins, 1 thousand organic compounds, various nucleic acids in the amount of 10-3 * 10 molecules. It is obvious that these cells are participating in a grandiose biological performance in which a huge number of biomolecules necessary for cell growth are routinely supplied. No less impressive is the metabolism of an adult, who maintains the same weight and body composition for approximately 40 years, although during this time he consumes about 6 tons of solid food and 37,850 liters of water. All substances in the body are converted (complex to simple and vice versa) by 2/3 of a series of sequential compounds, each of which is called a metabolite. Each transformation is a stage of metabolism.
The set of such successive stages catalyzed by individual enzymes is called a metabolic pathway. Metabolism is formed from the totality of figurative metabolic pathways and their joint functioning. This is carried out sequentially and not chaotically (synthesis of amino acids, breakdown of glucose, fatty acids, synthesis of purine bases). We know very little, hence the mechanism of action of medicinal substances is very transparent!!!
The entire metabolic pathway is usually controlled by the first - second stages of metabolism (limiting factor, enzymes with an allosteric center - regulatory).
Such stages are called key, and the metabolites at these stages are called key metabolites.
Metabolites located on cross metabolic pathways are called node metabolites.
There are cyclic metabolic pathways: a) usually another substance is involved and disappears; b) the cell gets by with a small amount of metabolites - savings. Control pathways for the conversion of essential nutrients
food
Shooting Range
Albinism Endemic goiter
homogent pigment. Thyroxine company
melanin
Alcapturia
carbon dioxide and water
Metabolism regulation
Each reaction occurs at a speed commensurate with the needs of the cell (“smart” cells!). These specific ones determine the regulation of metabolism.
I. Regulation of the rate of entry of metabolites into the cell (transport is influenced by water molecules and the concentration gradient).
a) simple diffusion (for example water)
b) passive transport (no energy consumption, for example pentoses)
c) active transport (carrier system, ATP)
II. Control of the amount of certain enzymes Suppression of enzyme synthesis by the end product of metabolism. This phenomenon represents a gross control of metabolism, for example, the synthesis of enzymes that synthesize GIS is suppressed in the presence of GIS in the bacterial culture medium. Rough control - since it is implemented over a long period of time while the finished enzyme molecules are destroyed. Induction of one or more enzymes by substrates (increase in the concentration of a specific enzyme). In mammals, a similar phenomenon is observed several hours or days later in response to an inducer.
III. Control of catalytic activity a) covalent (chemical) modification b) allosteric modification (+/-) bonds Modulation of activity by an already present enzyme is mainly allosteric regulation (homo-, hetero-, homoheteroenzymes) or the action of activators - this is a subtle regulation mechanism, so how it instantly acts in response to changes in the intracellular environment. These regulatory mechanisms are effective at the cellular and subcellular levels, at the intercellular and organ levels of regulation carried out by hormones, neurotransmitters, intracellular mediators, and prostaglandins.
Metabolic pathways:
1) catabolic
2) anabolic
3) amphobolytic (links the first two)
Catabolism- a sequence of enzymatic reactions, as a result of which destruction occurs mainly due to the oxidation reactions of large molecules (carbohydrates, proteins, lipids, nucleic acids) with the formation of light (lactic and acetic acids, carbon dioxide and water) and the release of energy contained in covalent bonds of various compounds, part of the energy is stored in the form of high-energy bonds, which are then used for mechanical work, transport of substances, and biosynthesis of large molecules.
There are three stages of catabolism:
Stage I - Digestion. Large food molecules are broken down into building blocks under the influence of digestive enzymes in the gastrointestinal tract, and 0.5-1% of the energy contained in bonds is released.
Stage II - Unification. A large number of products formed at stage 1 gives in stage 2 simpler products, the number of which is small, and about 30% of the energy is released. This stage is also valuable because the release of energy at this stage gives rise to the synthesis of ATP in oxygen-free (anaerobic) conditions, which is important for the body under hypoxic conditions.
Stage III - Krebs cycle. (tricarboxylic acids / citric acid). Essentially, this is the process of converting a two-carbon compound (acetic acid) into 2 moles of carbon dioxide, but this path is very complex, cyclic, multienzyme, the main supplier of electrons to the respiratory chain, and, accordingly, ATP molecules in the process of oxidative phosphorylation. Almost all enzymes of the cycle are located inside the mitochondria, so the electron donors of the TCA cycle freely donate electrons directly to the respiratory chain of the mitochondrial membrane system.
Diagram of the tricarboxylic acid cycle.
Succinyl CoA - contains a high-energy thioester bond that can be transformed into a high-energy GTP bond (substrate phosphorylation).
FAD - transfers electrons to CoQ of the respiratory chain: electron
alpha-ketoglutarate water isocitrate
alpha-ketoglutarate succinyl CoA CO2
In addition to everything, the TCA cycle is the 1st stage of anabolism at the same time.
Q=∆H + W
where: Q – heat energy
ΔН – enthalpy
W – work
So, cells, receiving from external environment energy in the form of light quanta (photosynthesis) or chemical energy of organic and inorganic substances, and storing it in compounds with high energy potential (ATP), converting it into electrical or chemical energy contained in a molecule. ATP is the main carrier of chemical energy in all living organisms. ATP can transfer its energy to other biomolecules, losing its terminal phosphate group, turning into ADP, that is, performing the work of contractile, musculoskeletal systems transport of substances across the membrane. Useless thermal work is released into the environment - the entropy of the environment (∆S) increases.
Second law of thermodynamics
The system strives for its disorder. This is documented by the increase in entropy ΔS and is expressed by the equation:
ΔH = ΔG + TΔS
where: ΔH – thermal energy,
ΔG – Gibbs free energy,
T – absolute temperature.
The entropy value is constant and has a positive minimum value. This occurs due to the fact that the increase in the level of entropy in the system during the degradation of nutrients is compensated by the removal of final products from the system and the intensification of biosynthetic processes, and this value is reduced to the required stationary parameters.
If metabolism stops, the Gibbs energy of the system decreases, entropy increases (that is, the quality of energy decreases), and enthalpy, which characterizes the measure of the thermal content of the system, decreases. It always strives for a minimum and when it is reached, the body dies. Therefore, the task of an organism or biosystem is a high level of enthalpy and free energy. The system tends to maintain the entropy value at a lower stationary level.
It is known that the higher the hardness of a substance, the lower its entropy. So the entropy of diamond (0.57 e.u.) is half the entropy of graphite (1.7 e.u.). Carbides, borides and other very hard substances are characterized by low entropy. The entropy of an amorphous body is slightly greater than the entropy of a crystalline one. An increase in the degree of dispersion of a system also leads to a slight increase in its entropy.
Entropy increases as the molecule of a substance becomes more complex; So for gases N 2 O, N 2 O 3, N 2 O 5 the entropy is 52.6, respectively; 73.4 and 85.0 e.u. The entropy of branched hydrocarbons is less than the entropy of unbranched hydrocarbons. The entropy of a cycloalkane is less than the entropy of its corresponding alkene.
Let us consider in more detail the factors necessary to maintain a steady state. In order for metabolism to take place, that is,
substrate S → X ↔ Y → P(end products of degradation)
implementation V 1, V 2, V 3 – const.
metabolism
the substrate concentration (S) must ensure saturation of the enzyme catalyzing this transformation. This reaction must be unidirectional, creating a net flow towards substrate degradation. Such reactions control the operation of the system and are its limiting links - they are kinetically irreversible. An example of such a reaction in the body is the glucokinase reaction, which leads to the formation of gl-6-phosphate from glucose in the presence of ATP and Mg 2+. This is the limiting link in glycolysis, which determines the speed of the process as a whole.
Conditions for maintaining a stationary flow.
1. The final stages of metabolism must be kinetically irreversible (CO 2 H 2 O);
2. Since the final products are excreted from the body, the entropy in the biosystem is maintained almost constant;
3. A constant flow of nutrients and energy is only one of the conditions for maintaining a steady state;
4. The presence of a structural organization that allows the absorption and use of nutrients and energy.
Introduction to metabolism. Principles of metabolic organization.
Metabolism- can be defined as the totality of all bioorganic reactions catalyzed by enzymes.
Intermediate exchange begins from the moment nutrients enter the blood and until the end products of metabolism are removed and provide the body with the substances and energy necessary for its life.
Metabolism is a highly integrated and focused process. Integration is possible due to the existence of a relationship between the metabolism of carbohydrates, proteins and fats, etc. The relationship is ensured by a common energy supply, common intermediate metabolites, at the level of which there is an intersection of specific metabolic processes (gl-6-ph, PVK, acetyl-CoA), general metabolic processes (TCA cycle, oxidative phosphorylation). Integration is also possible due to the relationship between tissues and organs. Integrating systems include nervous system(center for processing information and making decisions when conditions change); endocrine system(production of hormones that transmit information into the cell); vascular system(serves for the transport of not only nutrients, but also hormones).
The sequence of metabolism in the body allows us to distinguish 4 stages of metabolism, that is, metabolism is characterized by dynamism and stages.
Stage 1– at this stage, the supply of nutrients to the inner fabrics the body during digestion in the gastrointestinal tract. There are:
a) distant digestion - for example, the breakdown of proteins under the action of pepsin in the stomach cavity or trypsin in the intestinal lumen.
b) parietal or membrane - for example, the action of peptidases fixed on the surface of cells of the intestinal mucosa;
c) intracellular - for example, in lysosomes, digestion under the action of proteolytic enzymes.
In addition to the enzymes of the macroorganism, enzymes of the intestinal microflora also participate in digestion.
Stage 2– resorption – processes of absorption of nutrients through the intestinal mucosa.
Stage 3– interstitial metabolism – enzymatic processes of synthesis and breakdown, regulated by the neurohumoral pathway.
Stage 4– excretion – excretion of metabolic products.
The concept of the processes of catabolism and anabolism.
The set of chemical transformations of substances that occur in the body, starting from the moment they enter the blood and until the end products of metabolism are released from the body, is called intermediate metabolism(intermediate exchange). Intermediate metabolism can be divided into two processes - catabolism (dissimilation) and anabolism (assimilation).
Catabolism called the enzymatic breakdown of relatively large organic molecules, usually in higher organisms, by the oxidative route. Catabolism is accompanied by the release of energy contained in the complex structures of organic molecules and its storage in the form of the energy of phosphate bonds of ATP (exergonic process, with the release of Gibbs energy and storage in the form of ATP).
Anabolism is the enzymatic synthesis of large molecular cellular components, such as polysaccharides, nucleic acids, proteins, lipids, which are characterized by significant Gibbs energy and low entropy, as well as the synthesis of some biosynthetic precursors of simpler compounds with stronger bonds (low Gibbs energy values and high values entropy - CO 2, NH 3, urea, creatinine).
Anabolic processes occur in cells simultaneously and are inextricably linked with each other. Essentially, they should be considered not as two separate processes, but as two sides of a common process - metabolism, in which the transformation of substances is closely intertwined with the transformation of energy.
Catabolism.
The breakdown of basic nutrients in the cell is a series of sequential enzymatic reactions that make up the 3 main stages of catabolism (Hans Krebs) - dissimilation.
Stage 1– large organic molecules break down into their constituent specific structural blocks. Thus, polysaccharides are broken down into hexoses or pentoses, proteins into amino acids, nucleic acids into nucleotides and nucleosides, lipids into fatty acids, glycerides and other substances.
The amount of energy released at this stage is small - less than 1%.
Stage 2– even simpler molecules are formed, and the number of their types is significantly reduced. It is important to emphasize that here products are formed that are common to the metabolism of different substances - these are, as it were, nodes connecting different metabolic pathways. These include: pyruvate – formed during the breakdown of carbohydrates, lipids, amino acids; acetyl-CoA - combines the catabolism of fatty acids, carbohydrates, amino acids.
Products obtained at the 2nd stage of catabolism enter 3rd stage, which is known as the Krebs cycle - the tricarboxylic acid cycle (TCA), in which terminal oxidation processes occur. During this stage, all products are oxidized to CO 2 and H 2 O. Almost all the energy is released in the 2nd and 3rd stages of catabolism.
All of the above stages of catabolism or dissimilation, which are known as the “Krebs scheme,” most accurately reflect the most important principles of metabolism: convergence and unification. Convergence– the combination of various metabolic processes characteristic of individual types of substances into single ones common to all types. The next stage is unification– a gradual decrease in the number of participants in metabolic processes and the use of universal metabolic products in metabolic reactions.
At the first stage, the principle of unification is clearly visible: instead of many complex molecules of very different origins, fairly simple compounds are formed in the amount of 2-3 dozen. These reactions occur in the gastrointestinal tract and are not accompanied by excretion large quantity energy. It is usually dissipated as heat and is not used for other purposes. The importance of the chemical reactions of the first stage is to prepare the nutrients for the actual release of energy.
At the second stage, the principle of convergence is clearly visible: the merging of various metabolic pathways into a single channel - that is, into the 3rd stage.
At the 2nd stage, about 30% of the energy contained in nutrients is released. The remaining 60-70% of the energy is released in the tricarboxylic acid cycle and the associated terminal oxidation process. In the terminal oxidation system or respiratory chain, which is based on oxidative phosphorylation, unification reaches its peak. Dehydrogenases, which catalyze the oxidation of organic substances in the TCA cycle, transfer only hydrogen to the respiratory chain, which undergoes identical transformations in the process of oxidative phosphorylation.
Anabolism.
Anabolism also goes through three stages. The starting substances are those that undergo transformations at the 3rd stage of catabolism. Thus, stage 3 of catabolism is the initial stage of anabolism. The reactions of this stage have a dual function - amphibolic. For example, protein synthesis from amino acids.
Stage 2 – formation of amino acids from keto acids in transamination reactions.
Stage 3 – combining amino acids into polypeptide chains.
Also, as a result of sequential reactions, the synthesis of nucleic acids, lipids, and polysaccharides occurs.
In the 60-70s of the 20th century, it became clear that anabolism is not a simple reversal of catabolic reactions. This is due to the chemical characteristics of chemical reactions. A number of catabolic reactions are practically irreversible. Their flow in the opposite direction is prevented by insurmountable energy barriers. In the course of evolution, bypass reactions were developed that involved the expenditure of energy from high-energy compounds. The catabolic and anabolic pathways differ, as a rule, in their localization in the cell - structural regulation.
For example: the oxidation of fatty acids occurs in mitochondria, while the synthesis of fatty acids is catalyzed by a set of enzymes localized in the cytosol.
It is due to different localization that catabolic and anabolic processes in the cell can occur simultaneously.
Principles of Metabolic Integration
Thus, the metabolic pathways are diverse, but in this diversity lies unity, which is a specific feature of metabolism.
This unity lies in the fact that from bacteria to the highly organized tissue of a higher organism, the biochemical reactions are identical. Another manifestation of unity is the cyclical nature of the most important metabolic processes. For example, tricarboxylic acid cycle, urea cycle, pentose cycle. Apparently, cyclic reactions selected during evolution turned out to be optimal for ensuring physiological functions.
When analyzing the organization of metabolic processes in the body, the question naturally arises: how is the maintenance of processes achieved in accordance with the needs of the body in different periods his life activity? Those. How is “homeostasis” maintained (a concept that was first formulated by Cannon in 1929) in the face of constantly changing life situations, i.e. - when the internal and external environment changes. It was already mentioned above that the regulation of metabolism ultimately comes down to changes in enzyme activity. At the same time, we can talk about a hierarchy of metabolic regulation.
