METABOLISM AND ENERGY — set of processes of transformation of the substances and energy occurring in live organisms, both exchange of substances and energy between an organism and the environment. The metabolism and energy represents a basis of life activity and belongs to number of the major specific characters of living matter distinguishing live from lifeless. In the course of exchange the substances which came to an organism by chemical changes turn into own substances of fabrics and into end products, to-rye are removed from an organism. At these chemical transformations energy is released and absorbed. The metabolism, or metabolism, represents the high-integrated and purposeful process, in Krom the set of fermental systems participates and to-ry it is provided with the most difficult regulation at the different levels.
At all organisms cellular metabolism performs four main specific functions: 1) extraction of energy from the environment and its transformation to energy vysokoergichesky connections (see) in the quantity sufficient for ensuring all energy needs of a cell; 2) education from exogenous substances (or receiving in finished form) intermediate compounds, being predecessors of macromolecular components of a cell; 3) protein synthesis, nucleinic to - t, carbohydrates, lipids and other cellular components from these predecessors; 4) synthesis and destruction of special biomolecules, education and disintegration to-rykh are connected with performance of various specific functions of this cell. For understanding of essence of a metabolism and energy in zhi ~ j howl the cell needs to consider its power originality. All parts of a cell have approximately identical temperature, i.e. a cell on the substance of an izotermichn. Various parts of a cell differ also on pressure a little. It means that cells are not capable to use heat as an energy source since work with a constant pressure can be made only upon transition of heat from more heated zone to less heated. Thus, living cells are not similar to ordinary heat or electric motors. Living cell can be considered as the isothermal chemical car.
From the point of view of thermodynamics (see) live organisms represent open circuits as they exchange with the environment both energy, and substance, and at the same time will transform both. However they are not in balance with the environment and therefore can be called nonequilibrium open circuits. Nevertheless at observation during a certain interval of time in chemical structure of an organism of visible changes does not occur. But it does not mean that the chemical substances making an organism are not exposed to any transformations. On the contrary, they are constantly and rather intensively updated about what it is possible to judge by the speed of inclusion in complex substances of an organism stable and the radioisotopes entered into a cell as a part of simpler predecessors. The seeming constancy of chemical structure is explained by a so-called stationary state, i.e. such state of affairs, at Krom transport rate of substance and energy from the environment in system is precisely counterbalanced with transport rate from system on Wednesday. Thus, living cell represents nonequilibrium open stationary circuit.
- 1 Sources of carbon and energy for life activity
- 2 The circulation of nitrogen
- 3 The gross (total) metabolism and energy
- 4 Influence of various conditions on a metabolism and energy
- 5 An intermediate metabolism of substances
- 6 Regulation of a metabolism and energy
- 7 Disbolism and energy
- 8 Diagnosis of disbolism and energy
- 9 Prevention of disbolism and energy
- 10 Treatment of diseases of a metabolism of N of energy
- 11 Changes of a metabolism and energy in the course of aging
- 12 The metabolism and energy at children
- 13 Tables
Sources of carbon and energy for life activity
Depending on in what form of a cell receive from the environment carbon (see) and energy, all cells it is possible to divide into big groups. In a form of the received carbon of a cell are divided into autotrophic — «themselves feeding» (see. Autotrophic organisms ), using carbon dioxide as the only source of carbon (CO 2 ), from a cut they are capable to build all carbon-containing connections necessary to them; and heterotrophic — «eating at the expense of others» (see. Heterotrophic organisms ), not capable to acquire CO 2 and receiving carbon in the form of rather complex organic compounds, such, e.g., as glucose (see). In a form of the consumed energy of a cell can be phototrophic — directly using energy of a sunlight, and hemotrofny — living due to the chemical energy which is released during redoxreactions (see. biological oxidation ). The vast majority of autotrophic organisms is at the same time fototrofa. These are green cells of the higher plants, blue-green seaweed, photosynthesizing bacteria. Heterotrophs most often behave as hemotrof. All animals, the most part of microorganisms, not photosynthesizing cells of plants treat heterotrophs. The exception is represented by small group of bacteria (hydrogen, sulfuric, iron and denitrofitsiruyushchy), to-rye but to a form of the used energy hemotrofam are, but at the same time for them CO is a source of carbon 2 , i.e. on this sign they shall be carried to autotrophs.
Heterotrophic cells in turn can be divided into two big classes: aerobes, to-rye as final electron sink use oxygen, and anaerobe bacterias where as acceptors serve other substances. Many cells can exist both in aerobic, and in anaerobic conditions, call them facultative anaerobes. Other cells cannot use oxygen and even perish in its atmosphere, these are strict anaerobes.
Considering the biosphere in general, it is possible to notice that in sense of food all live organisms are anyway connected with each other. This phenomenon carries the name «sintro-fiya» (joint food). Fototro-fa and heterotrophs mutually feed each other. The first, being photosynthesizing organisms, form of the carbon dioxide which is contained in the atmosphere organic matters (e.g., glucose) and emit oxygen in the atmosphere; the second use glucose and oxygen in the course of metabolism inherent to them and as an end product of exchange return in the atmosphere of CO again 2 . This circulation of carbon in the nature is closely connected with a power cycle. Solar energy will be transformed in the course photosynthesis (see) in chemical energy of the recovered organic molecules, edges it is used by heterotrophs for a covering of the energy demands. The chemical energy received by heterotrophs, especially the higher organisms from the environment, partially turns directly into heat (maintenance of constant body temperature), and partially — into other forms of energy connected with different performance of work: mechanical (muscular contraction), electric (carrying out nervous impulse), chemical (the biosinteza proceeding with absorption of energy), the work connected with transport of substances (glands, intestines, kidneys, etc.). All these types of work can be totally considered on heat production.
It is necessary to emphasize that between exchange of substance and exchange of energy there is one basic distinction. The earth does not lose and does not receive a little noticeable amount of substance. Substance in the biosphere exchanges on a closed circuit and, thus, is reused. Energy exchange is carried out differently. It is not returned entirely on a closed circuit, and partially dissipates in external space. Therefore continuous inflow of energy of the Sun is necessary for maintenance of life on Earth. Amount of the energy participating in biol, circulation, hugely. In one year in the course of photosynthesis on the globe it is absorbed apprx. 10 21 kcal of solar energy. Though it makes only 0,02 all energy of the Sun, it immeasurably is more, than that energy, edges is used by all cars created by hands of the person. The amount of the substance participating in circulation is so high. It is enough to tell that the annual turnover of carbon makes 33•10 9 t.
The circulation of nitrogen
Other element, not less important for live organisms, than carbon, is nitrogen (see). It is necessary for protein synthesis and nucleinic to - t. As the main reserve of nitrogen on Earth serves the atmosphere, almost on 4/5 consisting of molecular nitrogen. However owing to chemical inertness of atmospheric nitrogen the majority of live organisms does not acquire it. Only nitrogen-fixing bacteriums have ability to recover molecular nitrogen and thus to transfer it to the connected state. Bound nitrogen makes a continuous circulation in the nature. The recovered nitrogen getting to the soil in the form of ammonia as a metabolic product at animals or formed by nitrogen-fixing bacteriums is exposed soil microorganisms to oxidation to nitrites and nitrates, to-rye get from the soil to the higher plants where are recovered with formation of amino acids, ammonia and some other nitrogen-containing products. These connections already in finished form get to an organism of the animals eating vegetable food then to an organism of the preying animals eating herbivorous and still in got into condition are returned to the soil then all cycle is repeated again.
The gross (total) metabolism and energy
Laws of perdurability of matter and energy formed a theoretical basis for development of the major method of a research of a metabolism and energy — establishments of balances, i.e. determination of amount of energy and the substances coming to an organism and leaving it in the form of heat and end products of exchange. Determination of balance of substances required creation enough exact chemical methods of their definition and knowledge of ways, on the Crimea various substances are emitted from an organism. It is known that the main feedstuffs are proteins (see), lipids (see. Fats ) and carbohydrates (see). As a rule, for assessment of content of proteins in food and in decomposition products it is enough to define amount of nitrogen since practically all nitrogen of food is in proteins, including in nucleoproteids; the insignificant amount of nitrogen which is a part of nek-ry lipids and carbohydrates in experiments by determination of nitrogenous balance can be neglected. Definition of lipids and carbohydrates in foodstuff demands specific methods, as for end products of lipid metabolism and carbohydrates, honor it only carbonic acid and water.
In the analysis of end products of exchange it is necessary to take into account to a way of allocation them from an organism. Nitrogen is emitted to hl. obr. with urine, but also both with a stake and in a small amount through skin, hair and nails (see. Nitrogen metabolism ). Carbon is emitted almost only in the form of CO 2 through lungs, but a nek-swarm its quantity is distinguished with urine and a stake. Hydrogen is excreted in the form of H20 preferential with urine and through lungs (water vapor), but also through skin and with a stake.
The balance of energy is defined on the basis of the caloric content of the entered feedstuffs and amount of the generated heat, a cut it can be measured or calculated (see. Calorimetry ). At the same time it is necessary to consider that the size of caloric content received at combustion of substances in calorimetric «bomb» can differ from fiziol, the caloric value since nek-ry substances in an organism do not burn down completely, and form the end products of exchange capable to further oxidation. First of all it concerns to squirrels, nitrogen to-rykh is emitted from an organism of hl. obr. in the form of the urea keeping a nek-ry potential stock of calories.
The important size characterizing features of exchange of separate substances is the respiratory coefficient (RC), to-ry is in number equal to the relation of volume of the exhaled CO 2 to the volume of the absorbed O 2 . It is easy to be convinced that for carbohydrates of recreation center it is equal 1, on the example of the equation of oxidation of glucose:
As the relation of volumes of gases is equal to the relation of number of their moths, the recreation center for this reaction is equal 6:6 = 1. Other picture turns out at lipid metabolism. E.g., in reaction of full oxidation of fat — palmitin of recreation center it is equal to 102: 145 = 0,703:
Thus, both the caloric value, and recreation center, and the size of heat generation expected 1 l of the consumed O 2 , for different substances are various. Average values of these sizes for the major feedstuffs are given in table 1. These data are widely used for the quantitative calculations connected with the characteristic of energy balance in an organism of animals and the person.
Distinguish direct and indirect methods of definition of metabolic rate and energy. In direct methods use a big calorimeter, with the help to-rogo way of the thinnest measurement of temperature define heat output and at the same time make a complete definition of balance of separate feedstuffs. In indirect methods, much simpler, only separate indicators of exchange, most often gas-metric define: quantity of the consumed O 2 and the allocated CO 2 in a definite time, and, besides, for assessment of protein metabolism define amount of the nitrogen emitted for the same time with urine. As the content of nitrogen in proteins is approximately constant and averages 16 g on 100 g of protein, 1 g of the emitted nitrogen there correspond 6,25 g of the protein involved in metabolism. Knowing amount of the protein metabolizing during experience and using the figures specified in table 1 calculate how many O 2 went for oxidation of protein and how many CO 2 it was allocated at the expense of protein. These quantities subtract from total quantity of O 2 and CO 2 , the experience measured in the course. As a result receive so-called nonprotein O 2 and CO 2 . From their ratio find nonprotein recreation center. By means of the data placed in table 2 in size of nonprotein recreation center find the general heat production at the expense of nonprotein substances and a share of carbohydrates and lipids in this heat production. Thus, on the basis of data on quantity of the absorbed O 2 , the exhaled CO 2 and the nitrogen emitted with urine for a certain span it can be calculated heat production (see) amounts of protein, the carbohydrates and lipids catabolizing for this period are also defined.
Influence of various conditions on a metabolism and energy
the Intensity of exchange estimated on the general power consumption can change depending on many conditions and first of all from physical activity. However and in a condition of absolute rest the metabolism and energy does not stop, and for ensuring continuous functioning of internals, maintenance of a tone of muscles and so forth the amount of energy is spent a nek-swarm. For assessment of specific features of exchange at different people agreed to make definition of intensity of exchange in reference conditions: at absolute physical and mental rest, in lying situation, not less than in 14 hours after the last meal, at the surrounding temperature providing feeling of comfort. The received size is called standard metabolism (see). At young men standard metabolism makes 1300 — 1600 kcal/days, or 40 kcal/m 2 / hour. At women the size of standard metabolism is 6 — 10% lower, than at men. With age (since 5 years) the size of standard metabolism steadily decreases (from 52,7 kcal/m 2 / hour at six-year-old boys to 34,2 kcal/m 2 / hour at men of 75 — 79 years). With fervescence on 1 ° the size of standard metabolism at the person increases approximately for 13%. Increase of intensity of exchange is observed also at decrease in ambient temperature below a zone of comfort. It is the adaptation process connected with need to maintain the constant body temperature (chemical thermal control).
During the comparison of standard metabolism at people of the different weight (weight) it was noticed that exchange is intensified with increase in the sizes of a body, but not in direct ratio to the weight (weight) of a body; big correlation is observed between standard metabolism and a body surface. This dependence for the first time established by M. Rubner received the name of the law of a surface. On Rubnera, at all hematothermal animals (birds and mammals) heat production irrespective of body weight makes in days apprx. 1000 kcal on 1 m 2 body surfaces. Later researches did not confirm these results. Theoretical value of researches of M. Rubner consists that it drew attention to a role of size of a body surface in a metabolism and energy since the body surface considerably determines heat waste by an organism by carrying out and radiation (see. Thermolysis ). Much more strict rectilinear dependence between the sizes of a body and a thermolysis is described by the equations found empirically, napr, Benedict's formula:
W = k*M 0,73 ,
where W — a thermolysis, M — body weight.
The main influence on the size of a metabolism and energy is rendered by physical activity. Exchange at an intensive exercise stress on power consumption can exceed by 10 times standard metabolism, and during very short periods (e.g., during the swimming on short distances) even by 100 times. The general daily need for calories is defined, first of all, by the nature of the performed work (see table 3).
At discussion of the factors influencing a metabolism and energy it is necessary to mention the special property of food called by its specific dynamic action (SDA). For a long time it was noticed that at consumption by the person or an animal of foodstuff the thermolysis increases at a size exceeding the number of the calories which are contained in the eaten food. This property, a cut was various for different feedstuffs, and SDD was called. Proteins differ in the highest SDD. It is considered to be that reception of protein with the potential caloric value of 100 kcal increases exchange to 130 kcal, i.e. SDD makes 30%. At carbohydrates and SDD fats is in limits of 4 — 6%. The SDD mechanism is not only that meal stimulates activity of the digestive device, SDD is shown also at intravenous administration of amino acids. The main thing in the SDD mechanism should be considered influence of foodstuff on an intermediate metabolism. So, calculations showed that the number of calories spent for education 1 asking ATP at metabolism of proteins, is about 30% higher, than at exchange of fats and carbohydrates.
An intermediate metabolism of substances
Set of chemical transformations of substances, to-rye come in an organism since the moment of intake of the digested feedstuffs in blood and until allocation of end products of exchange from an organism, call intermediate or interstitial metabolism (intermediate metabolism). Intermediate metabolism can be divided into two processes: catabolism (dissimilation) and anabolism (assimilation). The catabolism is the zymolysis of rather large organic molecules which is carried out at the higher organisms, as a rule, in the oxidizing way. The catabolism is followed by energy release, concluded in complex structures of large organic molecules, and its storage in the form of energy of phosphatic bonds of ATP. Anabolism is an enzymatic synthesis from simpler connections of krupnomolekulyarny cellular components, such as polysaccharides, nucleinic to - you, proteins, lipids, and also their nek-ry predecessors. Anabolic processes proceed with consumption of energy. The catabolism and anabolism occur in cells at the same time and are inseparably linked with each other. In essence, they should be considered not as two separate processes, and as two parties of one general process — metabolism, in Krom of transformation of substances are closely bound with energy conversions.
More detailed consideration of metabolic ways shows that splitting of the main feedstuffs in a cell represents a number of the consecutive enzymatic reactions making three main stages of a catabolism. At the first stage large organic molecules break up to the specific structural blocks making them. So, polysaccharides are split to hexoses or pentoses, a squirrel — to amino acids, nucleinic to - you — to nucleotides and nucleosides, lipids — to fat to - t, glycerin and other substances. All these reactions proceed in generally hydrolytic way, and the amount of the energy which is released at this stage is very small — less than 1%. At the second stage of a catabolism simpler molecules are formed, and the number of their types significantly decreases. It is very important that at the second stage products are formed, to-rye are the general for exchange of different substances. These products represent the key connections which are as if the junction stations connecting different ways of metabolism. Treat such connections, e.g., the pyruvate which is formed at disintegration of carbohydrates, fats and many amino acids; atsetil-KOA, in addition combining exchange fat to - t, carbohydrates and many amino acids; alpha ketoglutarate, oxaloacetate, fumarates also succinate, formed of different amino acids, etc. the Products formed at the second stage of a catabolism enter the third stage of a catabolism, edges is known under names of terminal oxidation, a cycle lemon to - you, a tricarbonic acid cycle, a cycle Tricarboxylic to - t (see. Tricarboxylic acids cycle ). During this stage all products eventually are oxidized to CO 2 and waters. Practically all energy is released at the second and third stages of a catabolism.
Process of anabolism passes through three stages too. As mother substances for it serve those products, to-rye are exposed to transformations at the third stage of a catabolism. Thus, the third stage of a catabolism is at the same time the first, initial stage of anabolism. The reactions proceeding at this stage perform as if double function. On the one hand, they participate in the final stages of a catabolism, and with another — serve also for anabolic processes, delivering prophetic stva - predecessors for the subsequent stages of anabolism. Quite often such reactions call amphibolic. At this stage, e.g., synthesis of protein begins. Initial reactions of this process can be considered formation of nek-ry alpha-ketonic acids. On following, the second, a stage during reactions of amination or transaminations (see) they turn into amino acids, to-rye at the third stage of anabolism combine in polypeptide chains. A number of consecutive reactions also synthesis nucleinic to - t results, from lipids and polysaccharides. It is necessary to emphasize that our knowledge of specific chemical ways of anabolism developed much later, than knowledge of reactions of a catabolism, and only in 60 — the 70th 20 century became clear that ways of anabolism are not the simple address of processes of a catabolism. It is connected with power features of chemical reactions. Nek-ry reactions of a catabolism are almost irreversible since their course in the opposite direction has an insuperable barrier in usual conditions. During evolution other, bypass reactions which allowed to bypass these barriers and to climb up the same power top let longer, but less abrupt way were developed.
Catabolic and anabolic ways differ, as a rule, and on the localization in a cell. E.g., oxidation fat to - t to acetate is carried out by means of a set of the enzymes localized in mitochondrions whereas synthesis fat to - t is catalyzed by other system of the enzymes which are localized in cytosol. Exactly thanks to different localization catabolic and anabolic processes in a cell can proceed at the same time.
Even such short review of ways of metabolism speaks about its extreme variety. However it is possible to see manifestation of surprising unity in this variety, a cut is the most typical and peculiar feature of a metabolism. This unity consists in what from bacteria to most is high - the differentiated fabric of the higher organism we meet with biochemical, reactions, not only externally similar, e.g., on the balance equations, on outer effects, but also absolutely identical in all details. Other manifestation of such unity should be considered the cyclic course of the major metabolic processes observed also on all way of evolution, napr, a cycle Tricarboxylic to - t, a cycle of urea, adenosinetriphosphate-ny a cycle, a pentozny way, etc. Probably, and biochemical, the reactions which are selected and fixed in the course of evolution and a cyclic way of their course were fittest for providing fiziol, functions of organisms.
Regulation of a metabolism and energy
Cellular metabolism is characterized by high stability and at the same time considerable variability. Both of these properties representing dialectic unity provide constant adaptation of cells and organisms to the changing conditions of surrounding and internal environment. So, the speed of a catabolism in a cell is defined by the need of a cell for energy at each this moment. In the same way the speed of biosynthesis of cellular components is defined by needs of this moment. The cell, e.g., synthesizes amino acids with that speed, edges is sufficient to provide a possibility of formation of the minimum quantity of protein necessary for it. Such profitability and flexibility of metabolism is possible only in the presence of rather thin and sensitive mechanisms of its regulation. Regulation of metabolic processes is carried out at the different levels of gradually increasing complexity. It is possible to speak about hierarchy of metabolic regulation. The primary type of regulation mentions all key parameters influencing the speed of enzymatic reactions. The size pH of the environment, concentration of a coenzyme, substrate, reaction product, existence of activators or inhibitors etc. concern to them. Influence on each of these parameters can change speed of response. E.g., accumulation of acid reaction products can shift pH of the environment out of limits of an optimum for this enzyme and thus slow down process. Quite often inhibitor of enzyme is substrate and in the presence of it in high concentration reaction does not go.
The following level of regulation of complex metabolic processes concerns multifermental reactions, to-rye represent the strict sequence of transformations and are catalyzed by the whole system of enzymes. In such system there are regulatory enzymes located usually in initial chain links of reactions. Regulatory enzymes are, as a rule, inhibited by an end product of this metabolic sequence. Thus, accumulation of reaction product to a certain concentration stops its further education. This phenomenon is called inhibition as a feed-back or retroingibirova-niy. On the mechanism the retroinhibition in most cases is allosteric, i.e. inhibitor affects not that active site of a surface of a molecule of enzyme, about the Crimea substrate communicates. Quite often specific modulators do not inhibit, and on the contrary, activate allosteric enzymes. Nek-ry allosteric enzymes of a polivalentna, i.e. can act on them two, three or even bigger number of the activators and inhibitors which are products of different metabolic processes. Such polyvalent allosteric enzymes can coordinate work of two or several fermental systems. Allosteric influence is extraordinary quickly, almost instantly changes activity of enzyme therefore this type of regulation can be considered as urgent, emergency.
The third level of regulation are the genetic control determining the speed of synthesis of enzymes, can strongly vary edges. Specific chemical signals can initiate or block a transcription of a certain site of DNA in information RNA depending on whether this signal the inductor or repres-litter will be. Regulation at the level of genes can lead to increase or reduction of concentration of these or those enzymes; to change of types of enzymes; to change of abundance in a cell of isoenzymes of this enzyme, to-rye, catalyzing the same reaction, differ on the catalytic properties. At last, in nek-ry cases induction or repression of at the same time whole group of enzymes can take place. It occurs when synthesis of all this group of enzymes is coded in DNA by a set of consistently located genes called operon (see). Genetic regulation differs in high specificity, profitability and provides ample opportunities for control of metabolism. However in the majority of cells gene activation process slow. Usually time necessary in order that the inductor or the repressor could affect considerably concentration of enzymes, is measured for hours. Therefore this form of regulation is unsuitable for urgent cases.
The highest animals and at the person have two more levels, two mechanisms of regulation of a metabolism and energy, to-rye differ in the fact that connect among themselves the metabolism which is made in different fabrics and bodies and thus direct and adapt it for performance of the functions inherent not in separate cells, but all organism in general. Such mechanism, first of all, is the endocrine system. Hormones (see), developed by closed glands, serve as the chemical mediators stimulating or suppressing certain metabolic processes in other fabrics or bodies. E.g., when the pancreas begins to produce less insulin, less glucose comes to cells, and it involves a number of secondary metabolic effects, in particular reduction of biosynthesis fat to - t from glucose and strengthening of formation of ketone bodies in a liver. Somatotropic hormone has effect opposite to insulin. It is known that the mechanism of effect of many hormones consists in activation of enzyme of the adenylatecyclase (KF 126.96.36.199) splitting ATP on cyclic 3', 5 '-AMF and an inorganic pyrophosphate. 3', 5 '-AMF called by the second intermediary transmits a specific signal of an intracellular target, i.e. through system 3', 5 '-AMF-zavisimykh protein kinases are modulated by activity of enzymes of cellular metabolism (see. Hormonal regulation ).
The highest level of regulation, its most perfect form is nervous control. The nervous system, in particular its central departments, performs the highest integrative functions in an organism. Receiving signals from the environment and from internals, c. the N of page will transform them and directs impulses to those bodies, change of speed of metabolism in to-rykh is necessary for performance of a certain function at present. Most often the nervous system carries out the regulating role through closed glands, strengthening or suppressing intake of hormones in blood. Influence of emotion on metabolism, napr, prestarting increase in indicators of a metabolism and energy at athletes, the strengthened products of adrenaline and the strengthening of sugar connected with it in blood at students is well known during the examinations, etc. In all cases the regulating action of a nervous system on a metabolism and energy is very reasonable and is always directed to the most effective adaptation of an organism to the changed conditions.
Disbolism and energy
Disbolism and energy are the cornerstone of all functional and organic damages of the bodies and fabrics leading to developing of a disease. The changes in course of chemical reactions happening at the same time are followed by big or smaller shifts in power processes. Distinguish 4 levels, on to-rykh there can be disbolism and energy: 1) molecular; 2) cellular; 3) organ and fabric; 4) complete organism. Disbolism and energy on any of these levels can have primary or secondary character. Their realization in all cases is enabled at molecular level, changes of a metabolism and energy on Krom and bring to patol, to disturbances of functions of an organism.
Normal course of metabolism at molecular level is caused by a harmonious combination of processes of a catabolism and anabolism. At disturbance of catabolic processes first of all there are power difficulties, regeneration of ATP, and also intake of initial substrates of anabolism, necessary for biosynthetic processes, is broken. In turn, primary or mediated by disturbances of processes of a catabolism damage of anabolic processes leads to disturbance of reproduction of functionally important connections — enzymes, hormones, etc. Damage of various links of metabolism on the effects is inadequate. The most essential, deep disturbances of a catabolism come at damage of system biol, oxidations (blockade of enzymes of tissue respiration, a hypoxia and so forth) or at damage of mechanisms of interface of tissue respiration and oxidizing phosphorylation (e.g., the separating effect at a thyrotoxicosis). Cells lose the main source of energy. Are blocked or lose ability to accumulate the released energy in molecules ATP almost all oxidizing reactions of a catabolism, being hydrogen donators. Approximately development of energy in reactions of a catabolism during the blocking of a cycle Tricarboxylic to - t, in particular its key reaction — synthesis lemon to - you, the inhibition of enzyme which is caused, e.g., tsitratsin-basins (KF 188.8.131.52) is reduced by two thirds, at a shortcoming pantothenic to - you, decrease in concentration oxalacetic to - you. At disturbance of a normal course of glycoclastic processes (glycolysis, a glycogenolysis), in particular their key reactions — hexokinase, fosfofruktokinazny and phosphorylase (see. Glycolysis ), the organism loses ability to adapt to a hypoxia that especially affects functioning of muscular tissue. Disturbance of use of carbohydrates, unique metabolic energy sources in the conditions of a lack of oxygen, one of the reasons of essential decrease in an animal force at patients with a diabetes mellitus. Weakening of glycoclastic processes complicates metabolic use of carbohydrates, leads to a hyperglycemia, switching of bio-energetics to lipidic and proteinaceous substrates, to oppression of a cycle Tricarboxylic to - t as a result of a shortcoming oxalacetic to - you. There are conditions for accumulation of nedookislenny metabolites — ketone bodies (see), disintegration of proteins amplifies, the gluconeogenesis is intensified. Develop acetonemia (see), azotemia (see), acidosis (see). Oxidizing decarboxylation pyroracemic to - you, broken at B 1 - avitaminosis, effect of the SH poisons blocking lipoic acid (see), at a shortcoming pantothenic to - you as KOA component and so forth, slow down final oxidation not only actually carbohydrate substrates, but also carbon skeletons of many amino acids, and also glycerin.
Utilization of lipids (see. Lipometabolism ) is at a loss during the braking of processes of a lipolysis (hydrolytic decomposition of molecules of various lipids), oppression of process of activation fat to - t with education acyl-S-KoA, phosphorylations of glycerin with the participation of a glitseratkinaza (KF 184.108.40.206). The last two processes suffer at insufficient regeneration of vysokoergichesky connections.
A catabolism of proteins and amino acids (see. Nitrogen metabolism ) it can be broken at deviations in processes of proteolysis, transamination, deamination, degradation of carbon skeletons of amino acids and at insolvency of systems of neutralization of nitrogenous slags — amidations of dicarbonic amino acids, biosynthesis of urea, formation of specific final derivative nitrogen-containing metabolites (uric to - you, creatinine, benzaminoacetic to - you, bilious pigments and their derivatives, etc.).
At disturbance of anabolism defects in system of biosynthesis nucleinic to - t and proteins have the leading value. Inborn or arising during ontogenesis mutations (see), disturbances of process of a transcription at synthesis of information and other RNA types, defects of maturing (processing) of information RNA, disturbances broadcastings (see), damages of posttranslya-tsionny formation of biologically active proteins — all this can lead to deep frustration of a metabolism and energy. Blocking of separate stages of synthesis of nucleotides and replaceable amino acids can be the reason of disturbances of synthesis nucleinic to - t and proteins also.
Disturbance of a gluconeogenesis — process of anabolism of carbohydrates (see Glycolysis) significantly affects maintenance of a power homeostasis of an organism. Special value has inhibition of the enzymes catalyzing a number of key reactions: mitochondrial and cytoplasmatic malate dehydrogenases (see. Malate dehydrogenase ), pyruvatecarboxymanholes (KF 220.127.116.11), the fosfoyenolpiruvatkarboksikinaza (KF 18.104.22.168) providing transformation pyroracemic to - you (pyruvate) in fosfoyenolpiruvat. The lack of these enzymes as a result of weakening of their synthesis can be observed at low level of secretion of AKTG and cortical hormones.
Biosynthesis of lipids can be broken at insufficiency of biotin (blocking of reaction of a carboxylation atsetil-KOA), and also at decrease in intensity of reactions of the pentozny way providing recovery reactions of biosynthesis. The lack of sincaline, methionine, unsaturated fat to - t, tsitidil-triphosphates affects synthesis of phospholipids. The deficit of pentoses arising during the blocking of a pentozny way significantly slows down synthesis of nucleotides, coenzymes of the nucleotide nature and nucleinic to - t.
The essential disbolism and energy connected with dysregulation of metabolism arise at disorder of processes of synthesis of biologically active agents, especially derivative amino acids (mediators, hormones, etc.).
At disbolism and energy at the cellular level first of all biomembranes are damaged (see. Membranes biological ), what involves disturbance of normal relationship of a cell with the environment, and also disturbance of cellular metabolism. The optimum topography of desmoenzymes, transmembrane transport, shuttle mechanisms of exchange of metabolites between various organellas of a cell fall apart. At damage of lysosomic membranes the autolysis of components of cytosol can begin lysosomic enzymes, at disturbance of an inner membrane of mitochondrions formation of ATP etc. stops. Disintegration of regulatory mechanisms of metabolism at the cellular level is an important consequence of damage of cellular membranes. Perception and further transfer on metabolism of a cell and strengthening of hormonal and nervous regulatory signals are broken: frustration of tsiklazny systems, transport of ions of Ca 2+ (see. Mineral metabolism ), disturbance of activity membrane ATFAZ, interactions of prostaglandins with membrane systems and so forth. Changes in a nuclear envelope and damages of structures of chromatin lead to disturbance of transfer of genetic information in cytosol, interfere with management of activity of chromatin from steroid hormones and intracellular regulators of protein synthesis. As a result of disturbance of processes of normal distribution of chromosomal material during cell fission (at early stages of an embryogenesis) chromosomal diseases with heavy disbolism and energy develop. Disorders of metabolism at the level of cellular structures can develop also as a result of autoimmune processes.
Depending on a specific role of these or those bodies and systems at disturbance of their function suffer a vzaimootnoshetion of intracellular metabolism with the environment, their adaptation to change of its conditions worsens (went. - kish. path, system of external respiration, etc.) or are broken a metabolic homeostasis of internal environment of an organism (a liver, kidneys, cardiovascular system, etc.) and regulatory processes (c. N of page, hemaden). Disturbance of bio-energetics of a brain is especially dangerous. Reserve power opportunities allow a brain to transfer the termination of delivery of power substrates (first of all glucose) and oxygen only within 3 — 5 min., than and reversibility of so-called clinical death is defined.
At the level of a complete organism at disbolism and energy the leading value has disorder of processes of regulation (loss of regulatory signals, their strengthening or a diskoordination owing to hypo - hyper - and dysfunctions of c. N of page and closed glands). Both loss of an innervation of bodies and fabrics, and the excessive or perverted impulsation lead to trophic frustration — atrophies, dystrophies. Mechanisms of these frustration are connected with change of normal interactions of mediators with cells, a diskoordination or loss funkts, interrelations in various parts of the nervous system. Easing or strengthening of production of hormones, disturbance of processes of their deposition, release, transport, interaction with receptors of target cells, an inactivation lead to development of characteristic frustration of a metabolism and energy of an organism in general as it takes place at a diabetes mellitus, a diffusion toxic craw, pituitary obesity, etc. Extreme forms of manifestation of these frustration are obesity (see) and cachexia (see), the coherences of a catabolism and anabolism which are followed by deep disturbances.
Disbolism and energy can be caused by action of both external, and internal factors. It is necessary to carry qualitative and quantitative changes as a part of food to external factors, intake of alien toxicants (including bacterial toxins), penetration into an organism of pathogenic microorganisms and viruses. Lack of irreplaceable amino acids (see) and fatty acids (see), microelements (see), vitamins (see), imbalance in the ratio proteins, fats and carbohydrates in food, discrepancy quantitative (on caloric content) and qualitative structure of food to specific energy expenditure of an organism, essential shifts in the size of partial pressure of oxygen and CO 2 in inhaled air, emergence in the atmosphere of carbon monoxide gas (CO), nitric oxides, other toxic gases, hit in an organism of ions of heavy metals, compounds of arsenic, cyanides, carcinogens, etc. is led to disbolism and energy. Final objects of influence of all listed factors most often are enzymes.
Genetically caused disturbances of synthesis of enzymes belong to internal factors (see. Enzymopathies ), transport proteins (hemoglobin, transferrin, ceruloplasmin, etc.), immune proteins, proteinaceous and peptide hormones, structural proteins of biomembranes, etc. As a result of genetically caused blocking of any enzyme or system of enzymes their not turned substrates — predecessors of the broken stage of metabolism collect. Blocking of hydrolases leads to development of diseases of accumulation (a glycogenous disease, glikozi-doses, etc.). In other cases the metabolites having toxic effect on an organism by secondary inhibition of these or those enzymes collect (e.g., the galactose or galaktit at a galactosemia, phenyl-pyruvic to - that at a fenilketonuriya, etc.). Disturbance of normal synthesis nek-ry especially important funkts, proteins, napr, hemoglobin (hemoglobinopathy), leads to a heavy fabric hypoxia or to other, not less dangerous states. The large number of other molecular diseases, the nature of frustration of a metabolism and energy is known at to-rykh is defined funkts, a role of defective protein.
A specific place is held by the frustration of a metabolism and energy developing at a malignancy of fabrics. Apparently, disturbances of regulation of processes of protein synthesis are the cornerstone of malignant growth. All further frustration of a metabolism and energy conducting eventually to a cachexia have a secondary origin.
Diagnosis of disbolism and energy
Diagnosis of disbolism and energy is based on results of researches of components of blood, urine, others biol, liquids, biopsies (see table 4). The total score of disbolism and energy can be received, defining standard metabolism (see), nitrogenous balance (see. Nitrogen metabolism ), size respiratory coefficient (see), shifts acid-base equilibrium (see) and other parameters. More detailed information is given by researches of concentration of separate metabolites, both normal, and pathological, usually not formed or not attendees in biol, liquids is normal. About depth of damages of cellular structure, and also about character of enzymopathies allow to judge enzimologichesky researches of blood serum organ localization of disturbances. Degree of a diskoordination of regulatory processes of a metabolism and energy can be estimated by a research of activity and concentration of hormones, mediators, prostaglandins, cyclic nucleotides, etc.
The disturbances of a metabolic homeostasis testimonial of shifts in neuroendocrinal regulation, can be established by means of the data obtained as a result of biochemical, blood test i.e. a direct way. However the data on intracellular exchange processes based on data biochemical of blood test, can have only indirect character. In nek-ry cases specification is possible at a research of biopsy material. Additional indirect data can be obtained by interpolation of results of a research of blood cells (leukocytes, erythrocytes) as model cellular systems. At assessment of metabolic shifts in c. N of page the research of cerebrospinal liquid is of particular importance.
Prevention of disbolism and energy
the Main way of prevention of disbolism and energy is evidence-based on qualitative and quantitative structure, the so-called balanced food vitaminized, containing all microelements, environment protection against penetration in it of toxicants, prevention inf. diseases, stressful situations, optimum duty and rest. In cases of endogenous disturbances (molecular diseases) early diagnosis and dietary prevention are important.
Treatment of diseases of a metabolism of N of energy
Treatment of diseases of a metabolism of N of energy is based on selection of the corresponding diet, on hormonal therapy, use of substances, tropny to separate hemadens, parenteral food, specific therapy of the disease which is the prime cause of disbolism and energy. Treatment of disbolism and energy at molecular diseases, in addition to a dietotherapy, symptomatic. The cardinal solution of a problem of therapy of these diseases is connected first of all with progress genetic engineering (see) and the directed regulation of activity of enzymes.
Changes of a metabolism and energy in the course of aging
Ageing is characterized by the uneven, multidirectional changes of a metabolism and energy leading to decrease in adaptation opportunities of the growing old organism and promoting developing of diseases. Primary mechanisms of aging are connected with changes in process of synthesis of protein. With age the Isoelectric point of a number of proteins, their hydrophily, ability to swelling changes, digestibility of proteins pepsin, trypsin changes, activation energy of proteolysis raises. During the aging the amount of metabolic active proteins decreases, and the mass of metabolic inert proteins, on the contrary, increases. At elderly people intensity of updating of proteins decreases. Synthesis of separate proteins in old age changes unevenly. All this leads to change of a ratio of various protein fractions. So, in old age in blood the content of globulins increases, concentration of albumine decreases and respectively decreases albumine-globulipovy coefficient (see). Assume, as proteolysis of separate proteins occurs with age unequally. Thanks to shifts in regulation of the genetic device during the aging contents and activity of separate enzymes, a ratio of isoenzymes, intensity of their synthesis unevenly change that creates a basis for disturbance of a number of recyclings.
During the aging there are also specific changes in exchange of carbohydrates. The mechanism of change of exchange of carbohydrates at advanced and senile age is connected with change of activity of glycolytic enzymes. On the nature of change of tolerance to glucose distinguish two groups from elderly and old people: with the normal and lowered tolerance which is characterized by longer and expressed hyperglycemia after loading glucose. Decrease in tolerance to carbohydrates is in many respects connected with decrease of the activity of insulin in blood, change of an iso-fermental range of a hexokinase, reduction of ability of fabrics to react to effect of hormones. Decrease in an old age of glikogendeponiruyushchy function of a liver is important. In the course of aging the glycoclastic way of transformation of carbohydrates in a myocardium, a brain, skeletal muscles is activated.
The disturbances in lipid metabolism arising in the course of aging promote development of atherosclerosis. They are noted also at almost healthy people, but are especially expressed at the age of 55 — 60 years. With age the general maintenance of lipids in blood and fabrics accrues, there is a lipoidosis of internals, the amount of cholesterol, triglycerides, not esterified fat to - t increases. Increase in contents is important (beta and pre - beta lipoproteids (see. Lipoproteids ), increase in content of the cholesterol connected with protein. At elderly and old people the content of cholesterol and triglycerides in lipoproteids of low and very low density increases, a cut remains without changes in lipoproteids of high density. At people of 60 — 74 years the content in blood and fabrics of atherogenous lipoproteids increases: lipoproteids of low and very low density. In genesis of disturbances of lipid metabolism during the aging decrease of the activity is of great importance lipoproteidlipaza (see), shifts in the ratio processes of synthesis and disintegration of triglycerides, cholesterol, disturbance of oxidizing processes in lipid metabolism, accumulation in fabrics of peroxides of lipids, disturbance of hormonal regulation of a lipogenesis and lipolysis.
The size of standard metabolism at elderly and old people steadily decreases. The senile organism becomes more sensitive and less steady against a lack of oxygen. During the aging respiration intensity of many fabrics decreases (tissues of a myocardium, brain, kidneys, etc.). It is in many respects connected with change of activity of separate links of a respiratory chain, with a lack of a number of substrates biol, oxidations. In old age the quantity got into condition by NAD and NADF increases, the topography of their distribution in a cell changes, the maintenance of a myoglobin decreases. During the aging intensity not only oxidations, but also phosphorylations decreases, in cells the number of mitochondrions decreases and it limits a possibility of a cell to form vysokoergichesky connections. Along with oppression of tissue respiration in a number of fabrics intensity of glycolysis increases, the oxidizing stage of a pentozofosfatny way is activated and intensity of not oxidizing decreases. Content of ATP unequally decreases in different bodies, its updating is slowed down. Considerably the maintenance of the major carrier of energy — creatine phosphate decreases, activity of a kreatinfosfokinaza decreases. Activity membrane To + Na + - ATP-ases decreases, and ATP-ases of a myosin accrues. All this complex of changes of a metabolism and energy limits funkts, possibilities of cells and bodies during the aging and promotes development of their insufficiency at the raised loadings.
The metabolism and energy at children
in the course of growth and development of an organism a metabolism and energy is exposed to quantitative and qualitative changes. Period ontogenesis (see) differs in the certain features of a metabolism and energy which are not repeating during further development. To each age period there corresponds such condition of metabolism, a cut provides a ratio of plastic and biopower processes, optimum for growth. It is conditionally possible to allocate a number of growth periods and development of an organism of the child, the Crimea svoystven a certain type of a metabolism and energy. Pre-natal development is characterized by existence of so-called critical periods of the maximum differentiation of fabrics, formations of bodies and systems (see. Fruit ). Perinatal period (see) distinguish active processes of metabolic adaptation in connection with the birth and transition to extra uterine existence. The period of chest age (see the Baby) is characterized by the maximum metabolic rate and energy, transition to the food independent of a maternal organism, development of functional systems and immunity. Relative stabilization of the main indicators of a metabolism and energy distinguishes the first 6 — 7 years of life. In the pubertal period it is replaced by the new reorganization of metabolism happening under the influence of sex hormones (see. Age ). All this does not allow to consider a metabolism and energy as simple, linear, function of growth; a number of the processes which are closely connected with a condition of a metabolism and energy and defining development of the child, in particular myelinations of nervous tissue ossification of bone matrixes, synthesis of functional proteins and sex hormones, proceeds asynchronously in relation to rates of physical development.
In the pre-natal period power substrates and plastic material arrive to a fruit through a placenta (see) with constant speed that is defined by a condition of homeostatic mechanisms of mother and vigorous activity of a placenta. Own mechanisms of regulation of a homeostasis at a fruit do not function. Special value for normal fetation has transplacental transport of oxygen. Partial pressure of oxygen in an arterial blood and saturation by its oxygen the fruit below, than at the adult, however has data that the fruit is provided with enough oxygen for implementation in it aerobic processes of power supply on an equal basis with anaerobic. It allows a fruit to adapt to conditions of a hypoxia (see). Oxygen and carbonic acid pass through a placenta by simple diffusion in the direction of more low partial pressure.
Fabrics of a fruit differ in high performance of extraction of oxygen from placental blood even with a low partial pressure of oxygen in it. Oxygen absorption a fruit by the time of the birth reaches 6,0 ml! kg in 1 min. that provides the course of aerobic processes.
Essential features are inherent also to mechanisms of extraction from fabrics of the carbon dioxide gas which is formed in processes of a metabolism and energy of a fruit. Transport of carbon dioxide gas is sharply shifted in the direction of maternal blood that is promoted by reduced activity karboangidraza (see) in erythrocytes of an ilod. Besides, continuous intake of oxygen from maternal blood favors to replacement of carbon dioxide gas from fabrics of a fruit (Golden's effect).
The placenta has ability actively, i.e. against a concentration gradient, to transfer and concentrate amino acids: in their umbilical blood contains almost twice more, than in blood of mother though in the course of pregnancy for the majority of amino acids this ratio gradually decreases (except taurine and threonine). Strengthening of amino acids in blood of mother is followed by sharper increase in their concentration in biol, liquids of a fruit (see. Nitrogen metabolism).
Transport of proteins through a placenta does not depend on the size of their molecules and is defined only by their specific structure. IgG about a pier. it is powerful (weighing) 160 O000svobodno passes through a placenta, and the molecules IgA having approximately the same pier. weight, through a placenta do not get; even smaller molecules of a gaptoglobin and transferrin do not come to blood of a fruit. In the placenta there is a synthesis of small amounts alpha and beta globulins, an also of fetoprotein, however this synthesis has no essential value for a fruit. The fetalis proteins, in particular gamma-globulin which are alien in relation to an organism of mother in small amounts come to her blood stream what emergence in maternal blood of antibodies to antigenic determinants From (a)7 - of globulin of a fruit testifies to. These antibodies, passing from mother into an organism of a fruit, suppress synthesis of own IgG of a fruit that, perhaps, and leads to development of a tranzitorny hypogammaglobulinemia of newborns.
In a placenta passive and active transport of glucose is carried out, edges is the main power substrate for a fruit. Between an organism of mother and a fruit there is a constant exchange fat to-tami, for to-rykh a placenta is freely passable. At the end of pregnancy activity of lipolytic enzymes increases in blood serum of mother that promotes receipt of additional quantities fat to - t to a fruit. Own lipids, to-rye synthesize a fruit, differ on structure from lipids of mother in higher content saturated fat to - t, in particular palmitic. The organism of mother, a placenta and a fruit represent uniform neuroendocrinal system (see. Antenatal period). Practically all hormones of mother (except peptide) are capable to pass through a placenta. The termination of intake of maternal hormones, including placental and estrogen, and also a patrimonial stress play an essential role in processes of metabolic adaptation of newborns.
Metabolic adaptation of newborns is shown as a complex of qualitatively new exchange reactions of the substances and energy interfaced to change or the beginning of functioning of a number of bodies and systems that in general defines viability of the newborn (see). In the course of childbirth there comes tranzitorny restriction of transport of oxygen: the born child appears in the conditions of a hypoxia. Ability of switching of energy balance inherent to a fruit and the newborn on anaerobic glycolysis (see) serves as the most important guarantee of its existence. At a fruit and the newborn the hypoxia activates enzymes of glycolysis whereas at adults, on the contrary, suppresses them. At the long or complicated childbirth the threat of accumulation in fabrics of a fruit of surplus milk to - you — the key end product of anaerobic glycolysis, and also other nedookislenny products is created that creates threat of development of the heavy metabolic acidosis (see) which is quite often leading to defeat of c. N of page. However newborns have acidosis easier, than adults.
Transition to extra uterine existence demands inclusion of the major functional systems of an organism, functioning to-rykh was not necessary for life support of a fruit — nervous and endocrine systems, external respiration, digestion and homeostatic activity of kidneys. At the same time paramount value gains ability of an organism of the newborn to independently regulate a homeostasis and first of all constancy of balance of acids and the bases, osmotic pressure (see), ionic structure and volume of liquids of an organism (see the Water salt metabolism), and also concentration of glucose in blood. After the delivery uniform intake of power substrates and plastic materials from blood of mother is replaced by their discontinuous delivery with food.
A maturity of functional systems of a homeostasis (see) depends on extent of development or the beginning of synthesis of enzymes that is connected with derepression of the corresponding regulator genes. Synthesis of a number of proteins-enzymes is induced by a tranzitorny hypoxia, a patrimonial stress, and also intake of various exogenous nutrients, new to an organism. Further biosynthesis of proteins-enzymes is regulated by the neuroendocrinal system controlling their products at the level of broadcast of genetic information or at the level of ribosomes. In the period of a neonatality a number of hereditary defects of fermental systems is shown, to-rye till the birth were in whole or in part compensated by an organism of mother — renal canalicular acidosis (see Laytvud — Albright a syndrome), a lactacidemia (see), a galactosemia (see), a giperam-moniyemiya (see) etc.
Transition from conditions of thermal balance on Wednesday with the lowered and fluctuating temperature causes inclusion in the newborn of own system of thermal control (see), edges by this moment is still imperfect since the neyrososudi-sty and muscular reactions directed to preservation of heat at newborns are insufficiently developed. Standard temperature of newborns is maintained in limits 36,5 — 37,5 ° at ambient temperature 23 — 24 °. Because of imperfection of system of thermal control more high temperature of the environment, indicators a cut is necessary for premature children are in inverse relation with degree of prematurity.
After the birth and up to 3 years inclusive intensity of energy balance at children increases, reaching the level exceeding that at adults per the weight or a body surface. Inverse relation between the linear sizes of a body of the child and a metabolic cost on unit of his weight is established; in process of delay of growth rates intensity of energy balance decreases.
In the course of childbirth processes of a glycogenolysis are the main power source for a fruit (see the Glycogen), to-rye amplify together with the beginning of patrimonial activity. By the time of the birth stocks of a glycogen at a fruit are practically exhausted therefore energy demands of the newborn in the first days of life are satisfied for the account [3 oxidations fat to - the t which are released as a result of activation of processes of a lipolysis.
According to Daniel (N. Daniel) and Derry (D. M of Derry), the major role in maintenance of a heat balance at newborns is played by brown fatty tissue (see), edges is the main source to heat production (see). Activation of processes of a gluconeogenesis represents one more way of maintenance of a power homeostasis.
The size of a respiratory coefficient (see) soon after the birth makes 0,83 and during the first hours lives decreases to 0,7 that demonstrates switching of energy balance from the prevailing use of glucose as power substrate on utilization of fat. By data Steyva (U. Stave, 1970), administration of glucose of mother before childbirth prevents mobilization of fat.
The size of standard metabolism (see) in the period of a neonatality more than twice exceeds this indicator at adults. The high level of standard metabolism remains approximately to 4-year age, but also then it remains to more intensive, than at adults. At boys in all age periods standard metabolism is higher, than at girls, and distinction is shown already in 6 — 8-month age; there is no explanation for this fact yet. Dynamics of age changes of standard metabolism is in a certain correlation with function of a thyroid gland (see): at newborns and children of the first year of life very high secretion of thyroid hormones is noted, the edge decreases a little by 3 — 4 years of life and increases in teenage age again.
Interface of processes of oxidation (see biological oxidation) and phosphorylations (see) is established in development of the child. In the embryonal period it insufficiently that defines ease of switching of energy balance to glycolysis (see). Increase of tissue respiration in the course of growth is followed by braking of glycolysis (see Pasteur effect).
Fabrics of a fruit and the newborn are rather provided to ATP. The summary contents of ATP, ADF and AMF in a liver of a fruit same, as well as in a liver of mother. Nek-roye decrease in content of ATP in tissues of the newborn is noted directly after the delivery and is traced only for the first days of life. Content of ATP in blood at early children's age is about 30% higher, than at adults.
In the course of growth and development of the child the ratio between the main phases of a metabolism and energy — assimilation (see) and dissimilation gradually changes (see).
In the fetalis period processes not only synthesis, but also a catabolism of proteins are accelerated (see). In the period of a neonatality there is a short-term catabolic phase of a metabolism when processes of disintegration of proteins prevail over their synthesis. During this period of a squirrel are partially used as power substrate, especially at limited reserves of fat (e.g., at children with small body weight at the birth). On 3 — the 4th day of life negative nitrogen balance is replaced by positive. In the course of growth increase in weight of the child by 100 g is followed by a delay in an organism of 2,9 g of nitrogen and 18 g of protein, i.e. processes of synthesis prevail over processes of disintegration. Development and formation of functions of bodies and systems is directly or indirectly connected with metabolism of proteins. Increase in lump of proteins in an organism most intensively during the early age periods. Changes of an anabolic phase of protein metabolism in ontogenesis are expressed not only in decrease in protein synthesis in connection with gradual delay of growth rates, but also in various speed of accumulation of specific proteins. Intensity of protein synthesis is defined by the content of nucleic acids (see) in fabrics, and there is a direct dependence between a weight gain, protein content and a ratio of RNA and DNA. In the antenatal period and on the first year of life in fabrics the highest content of DNA is noted; after the birth its synthesis is slowed down parallel to decrease of the activity of DNA polymerases (see Polymerases). In a cardiac muscle the content of DNA gradually decreases by 15 years and further significantly does not change. In a brain the content of DNA begins to decrease already ^ the first months of life whereas synthesis of protein and a myelin accrues. The oppression of DNA replication connected with reduction of number of the sharing cells is combined with increase of synthesis DNK-zavisi-moy RNA polymerases. High content of ribosomal RNA in a myocardium, muscles and a liver is explained by it.
Total quantity of protein in an organism of a fruit makes less than 10% of its weight, newborns have 10 — 12%, adults have 18 — 20%. Processes of synthesis of protein in a liver, kidneys, a brain, skin are most intensive. The periods of acceleration and delay of synthesis of protein in various bodies of the growing organism do not match. In fabrics of a children's organism the hydrophilic, quickly renewed proteins prevail, and only by the pubertal period the amount of the proteins differing in more rigid structure and smaller hydrophily increases. Increase in content of collagen (see) in fabrics in the course of growth it is connected with delay of speed of its updating, at the same time rigidity of its structure increases. In muscular tissue the content of myoalbumin decreases with age and the quantity of a myoglobin increases.
One of essential features of a metabolism and energy at early stages of ontogenesis is synthesis of embriospetsifichesky proteins like fetoproteins. According to V. A. Tabolin and sotr. (1978), contents and - fetoprotein in umbilical blood at the full-term newborns averages 20 zhg/100 ml. At the child with a small weight at the birth it the is more, than less its weight. In the course of growth concentration and - fetoprotein in a blood plasma decreases (increase in its concentration in blood serum at adults is characteristic of malignant new growths in a liver). Increase in contents and - fetoprotein in an amniotic fluid testifies to inborn malformations at a fruit that is used for antenatal diagnosis. Long preservation of synthesis of large numbers and - fetoprotein or its strengthening is observed at dragged on fiziol, jaundice, an atresia of bilious ways, and also at inborn and neonatal hepatitis.
With age the proteinaceous range of a blood plasma changes (see); by the time of the birth of the highest intensity reaches synthesis of albumine, education and - and r-globulins is considerably reduced and synthesis at - globulins is very limited. Higher, than at mother, the maintenance of ^-globuli-n in blood serum of newborns explained it with placental synthesis earlier, but then it was revealed that in a placenta takes place not only synthesis, but also selective transport of IgG. The maintenance of IgG in blood becomes same as at adults, to 1 — to the 6th year of life, and these terms are subject to considerable individual fluctuations. Unlike formation of IgG synthesis of own IgM is carried out by a fruit on the 5th week of pre-natal development. (Intake of antigens through a placenta, pre-natal infection) the fruit answers an antigen challenge with increase in synthesis of IgM. The maintenance of IgM more than 30 mg / 100 ml demonstrates pre-natal contact of a fruit with antigens.
At newborns very low concentration in blood of ceruloplasmin — apprx. 20% of its concentration in blood of mother is defined. Gradual increase in synthesis of ceruloplasmin begins on the 7th month of life. Gaptoglobin (see) in umbilical blood right after the birth is found only in 8% of newborns, but by the end of the first week of life it appears at all children.
Synthesis of a number of proteinaceous components of coagulant system of blood (see) at a fruit and the newborn is insufficient. At children with a small weight at the birth concentration of a prothrombin in blood is even lower, than at full-term. Administration of phthiocol of mother before childbirth or to the newborn eliminates a prothrombinopenia. In plasma of healthy newborns the high content of heparin is established, however at a hypoxia the tendency to increase in coagulability of blood develops. A fibrinolysis (see) in the period of a neonatality it is carried out much more intensively, than at adults.
Development of a children's organism is followed by change of forms of the organization of enzymatic processes, including high-quality and quantitative shifts of a range of isoenzymes in fabrics. These processes are determined genetically: inclusion of new regulatory genes at various stages of development changes the course of plastic processes, leads to emergence of the new proteins characteristic of more mature fabrics. At the same time the periods of a quantitative weight gain of a body and bodies in development alternate with the periods of a differentiation of fabrics. After the birth along with genetic factors process of a differentiation define system factors, the predominating role among to-rykh the neuroendocrinal system plays. These factors provide self-control of anabolic and catabolic processes, provide adaptation of a metabolism and energy of the growing organism. At early stages of post-natal life activity of many enzymes decreases, especially those from them, to-rye are connected with specific features of a metabolism and energy and development of bodies and fabrics in the pre-natal period or in the period of a neonatality. Data on the nature of changes of activity of enzymes (see) in the course of growth of the child are still very limited, and sometimes and are contradictory. However only the fact that age changes of enzymatic activity in ontogenesis are not subordinated to uniform pattern is undoubted. Activity of many enzymes increases after the birth, reaching at different times the level of their activity at adults. It depends on structure of bodies, fabrics, and also on features of a genotype of the child. Such nature of changes is connected with increase in intensity or formation of new metabolic ways. With age activity of oxidizing enzymes and enzymes of oxidizing phosphorylation, in fabrics increases the maintenance of adipic and flavin nucleotides increases that demonstrates increase of intensity of oxidation-reduction processes. However activity of oxidoreductases (see) in different bodies changes unequally, but most intensively — in a liver. High activity of nek-ry enzymes in blood serum of newborns is caused by a hyperpermeability of their cellular membranes (see Membranes biological), and in process of its decrease activity of these enzymes is normalized, approaching the sizes characteristic of adults. It is established for aspartate aminotransferase (KF 22.214.171.124) and fruktozo-bisfosfat-zymohexase (KF 126.96.36.199). Decrease of the activity of these enzymes in blood serum is noted at healthy children after 6 months though in a liver it remains high. Activity of lysosomic hydrolases is not exposed to essential age changes.
Insufficient intake or excess of separate amino acids (see) negatively influences process of protein synthesis owing to an amino-acid imbalance. Except irreplaceable amino acids, the histidine and a leucine, at a fruit and premature — cysteine-cystine since in their organism synthesis of these amino acids from methionine is sharply limited owing to insufficiency of a tsistationaza (KF 188.8.131.52) belong to the category of the first months of life, essential at children.
Certain features at children characterize lipidic exchange (see the Lipometabolism). Ability to synthesis unsaturated fat to - t at children, especially chest age, is limited therefore the increased receipt them with food is required. At early children's age are essential polinasy-shchenny fat to - you (linoleic, arachidonic), optimum receipt to-rykh on a power equivalent shall make 3 — 6% of the general need for calories. Value of these acids is especially big for synthesis of prostaglandins (see), contents to-rykh in tissues of newborns is 5 — 6 times higher, than at adults. Deficit polyunsaturated to - t is shown by a growth inhibition, development of a dermatosis, inferiority of an erythrogenesis (anemia).
During the first hours lives of the newborn play a major role in stimulation of a lipolysis AKTG of a fruit, ho-riongonadotropin and adrenaline. However sharp strengthening of a lipolysis for it is not indifferent since high concentration fat to - t can have toxic effect on tissue respiration. Besides, fat to - you with a long carbon chain do not pass through a blood-brain barrier. Therefore the main power substrate for a brain is glucose (see) and ketone bodies (see). Consumption of ketone bodies in a brain of newborns happens by 3 — 4 times more intensively, than at adults. At early children's age they are used by tissue of a brain also for synthesis of the fatty acids necessary for its myelination. Ketone bodies suppress lipolytic processes and by that prevent excessive strengthening of fatty acids.
The beginning of gas exchange in lungs, increase in partial pressure of oxygen in blood and receipt with food polyunsaturated fat to - t promote formation of peroxides of lipids, to-rye reduce stability of membrane structures, and also are a source of excess synthesis of prostaglandins in fabrics. In easy newborns right after the birth peroxide oxidation of lipids is practically absent, but in the first days of life it sharply increases that is also promoted by very low content of tocopherol in blood and fabrics, especially at the children who are on artificial feeding. Endogenous antioxidants (e.g., glutathione) do not play an essential role as factors of protection of cellular membranes against toxic effect of peroxides since their concentration in blood significantly does not change with age.
The lipogenesis is stimulated with glucose especially intensively in chest age. At administration of glucose the speed of inclusion palmitic to - you in triglycerides of fatty tissue of newborns increase approximately by 3 times, at babies — in time, at children of school age and adults approximately by 4 times. Oppression of synthesis of phospholipids of a brain and disturbance of processes of myelination is established at insufficiency of function of a thyroid gland. The hypoxia leads to permanent change of lipidic structure of a brain.
The main distinctive feature of carbohydrate metabolism (see) at a fruit high intensity of processes of glycolysis is: at newborns it is 30 — 35% higher, than at adults, and decreases in the first months after the birth.
Contents milk to - you in blood of newborns during the first hours reach life 32,5 mg! 100 ml also decrease for the 3rd days to 19 mg / 100 ml; concentration pyroracemic to - you decreases from 2,5 mg! 100 ml to 1,95 zhg/100 ml. If concentration milk to - you in blood in the first days of life more than by 10 times exceeds concentration pyroracemic to - you, it indicates a persistent hypoxia. High activity of glycolysis is connected with escaping of mitochondrions in cytoplasm of cells of the specific proteinaceous factor stimulating this process. Researches with 14C-glucose showed that its considerable part at a fruit is oxidized in a pentozofosfatny way. The ratio of activity of enzymes of glycolysis and a pentozny way at newborns and adults makes 1,2 — 2,1 and 1,1 — 2,6 respectively. In blood of a fruit fructose and sorbitol are found that indicates existence of an additional way of metabolism of glucose. Adults have this way fiziol, does not matter.
The maintenance of a glycogen (see) in a liver of a fruit in recent weeks reaches pregnancy 10% of all mass of body, but within the first days of life it decreases approximately by 10 times. In muscles the maintenance of a glycogen does not exceed 3%. However the general stocks of a glycogen at the newborn are rather small. Due to exhaustion of stocks of a glycogen at the time of delivery the content of glucose in blood falls to such values, to-rye at adults inevitably lead to development of a hypoglycemic coma (to 26 mg! 100 ml, at premature even to 20 mg! 100 ml of plasma). The heavy gipoglyukozemiya menacing with defeat of c. N of page, observe at the full-term newborns with a frequency of 1: 3000, is more often at boys. At children with a small weight at the birth frequency to hypoglucose-mii reaches 6%.
(See) are the main reasons of a heavy hypoglycemia: bystry exhaustion of reserves of carbohydrates that is promoted by a pre-natal hypotrophy, placental insufficiency; intensive absorption of glucose at a hypoxia and cooling; possible insufficiency of function of bark of adrenal glands; a hyper dysinsulinism of newborns from mothers suffering from a diabetes mellitus or at an eritroblastoza of a fruit; hereditary anomalies of exchange of carbohydrates — a galactosemia, glycogenoses (I, III, VI types according to Cory). Low activity a glycogen (starch) - synthases (KF 184.108.40.206) of an antenatal life can be in recent months one of the reasons of a hypoglycemia of newborns. Decrease in content of glucose in blood leads to strengthening of secretion of a glucagon (see) and to strengthening of processes of a glycogenolysis. At a hypoglycemia there is a stimulation of processes of a gluconeogenesis that for newborns is more important adaptation reaction in response to decrease in sugar in blood. During the first 3 — 4 days of life the content of glucose in blood of the newborn gradually increases. However tendency to hypoglycemic reactions continues to remain both in early children's and at preschool age; concentration of glucose in blood is stabilized only after 7 years.
Intravenous administration to children of the first days of life of a galactose in number of 1 gyg leads to strengthening of glucose in blood. After loading fructose the content of glucose in blood decreases at simultaneous sharp increase in concentration milk to - you. Test of Shtauba — Traugotta on existence of the latent forms of a diabetes mellitus (the loading grape sugar made on an empty stomach is repeated in half an hour after the first reception) at newborns reveals such type of reaction, to-ry at children of advanced age and adults it is considered pathological: the high and steep slope of a sugar curve is noted. Low secretion of insulin or reduced fabric sensitivity to it can be the cause of such reaction. However the insulinemiya in response to loading is expressed by glucose in a smaller degree at children aged from 6 months up to 2 years; this reaction reaches the fullest development only after 6 years.
On the first year of life the main carbohydrate of food is lactose (see), edges gradually gives way to starch and sucrose. Enzymic hydrolysis of lactose in intestines at the newborn is a little reduced, however increases and reaches a maximum at chest age, and then gradually decreases. About 20% of need for calories at chest age are provided at the expense of a galactose (see). And premature in the first days and weeks of life the galactose is found in healthy newborns in blood and urine; its exchange is more intensive, than at adults.
During puberty the pubertal jump of growth caused by effect of sex hormones is observed. The differentiation of fabrics is accompanied by further decrease in content of DNA in this connection on reaching a maturity cell fission is slowed down and growth rates more and more restrain. However in the pubertal period note new strengthening of anabolic processes. The growth hormone does not play an essential role in the course of pubertal acceleration of growth, in any case its concentration in blood during this period does not increase. The undoubted stimulating impact on metabolism in the pubertal period is exerted by activation of functions of a thyroid gland. Assume also that during puberty intensity of lipolytic processes decreases. In this period sulphation of glikozaminoglikan (activation of somatomedins) is considerably intensified. Removal with urine of oxyproline, glikozaminoglikan and creatinine decreases that can be connected with an intensification of synthesis of collagen and proteins of muscular tissue.
Regulation of a homeostasis in the teenage period becomes most ustoichivo therefore heavy a wedge, the syndromes connected with disturbances of regulation of exchange, ionic composition of liquids of a body, acid-base balance at this age do not meet any more.
Pathology of a metabolism and energy at children's age can be caused by hereditary and exogenous factors. Disturbance of processes of replication or a reparation of the damaged DNA in critical periods of pre-natal development involves formation of malformations (see Embryopathies), at the same time the nature of these defects (multiple or isolated) depends on age of an embryo, but not on the specific nature of the damaging influence (genovariation, a viral infection, toxic, radiation defeats). Considerable disturbances of metabolic adaptation in intranatal the period or at newborns are shown as a symptom complex of a birth trauma with defeat of c. N of page or lead to death of the child.
At early children's age at various infections and disturbances of food disturbances of a homeostasis (see), a toxic syndrome (see), dehydration (see Dehydration of an organism), acidosis (see), proteinaceous and power insufficiency especially often develop (see the Kwasiorkor). Disturbances of anabolic processes are shown in a growth inhibition that can be connected with insufficient secretion of somatotropic hormone (see), neuroendocrinal diseases — a hypothyroidism (see), a pituitary nanism (see Dwarfism), and also hypovitaminoses (see. A vitamin deficiency), rickets (see), hron, inflammatory processes. Inf. the diseases affecting a nervous system lead to disturbances of process of myelination of a brain, causing thereby a delay of neuro mental development of the child. The majority of hereditary diseases of exchange is shown at chest and early children's age (see. Hereditary diseases, Enzymopathies). Disturbances of biosynthesis of proteins of plasmatic and secretory immunoglobulins are followed by development of immunodeficiency (see. Immunological insufficiency). Instability of regulation of carbohydrate metabolism at early children's age creates premises for emergence of hypoglycemic reactions, acetone-michesky vomiting. Juvenile forms of a diabetes mellitus are early shown (see a diabetes mellitus). The most frequent pathology of lipid metabolism includes such states as obesity (see), and also the giperlipoproteinemiya (see Lipoproteids) which are risk factors in relation to early forms of coronary heart disease and an idiopathic hypertensia. Frequent the reason causing disbolism at children is deficit of microelements (see).
The general principles of correction of the broken metabolism and energy at children are as follows: any intervention in exchange processes of the sick child shall be controlled by means of corresponding biochemical, tests; the most effective method of recovery of the broken metabolism and energy at children is the balanced food (dietotherapy); induction of a number of enzymes can be reached by means of introduction of adrenal hormones or a thyroid gland, and also nek-ry pharmaceuticals, napr, barbiturates at insufficiency a glycogen (starch) - synthases or glucuronyl-transferase; a perspective method of impact on the broken metabolism and energy at children is development to lay down. uses of the immobilized enzymes, in particular the enzymes concluded in liposomes (see).
Table 1. Sizes of caloric content during the burning, the physiological caloric value, quantity of the consumed O 2 and the allocated CO 2 , heat generation and a respiratory coefficient for the major feedstuffs
Table 2. Sizes of respiratory coefficient, heat production and a caloric equivalent of oxygen at consumption of various mixes of lipids and carbohydrates
Table 3. Normal amounts of daily need for calories for urban population depending on a kind of activity (data of Institute of food of the USSR Academy of Medical Sciences)
Table 4. Some data on levels of disbolism ii of energy, their character, reasons and diagnosis
Bibliography: Berkovich E. M. Energy balance is normal also of pathology, M., 1964; Ford E. Evolution of biopower processes, the lane with English, M., 1978, bibliogr.; B at z N and to I. M. Energy balance and food, M., 1978, bibliogr.; Vanyushin B. F. and Berdyshev of G. D. Molekulyarno-genetiche-skiye mechanisms of aging, M., 1977; Introduction to clinical biochemistry (a basis of a patobiokhimiya), under the editorship of I. I. Ivanov, JI., 1969; Galler G., Ghana-feld M. and Yaross of Century. Disturbances of lipidic exchange, the lane with it., M., 1979; The Homeostasis, under the editorship of P. D. Gorizontov, M., 1976; Gorzheysha Ya., etc. Fundamentals of clinical biochemistry in clinic of internal diseases, the lane from Czeches., Prague, 1967; Davydovsky I. M. General pathology of the person, M., 1969; Zbareky B. I., Ivanov I. I. and Mardashev S. R. Biological chemistry, M., 1972; 3 about oozes A. I. Thermodynamic approach to problems of development, growth and aging, M., 1974; To about republics and the p B. And. Role of AKTG and glucocorticoids in regulation of energy balance, Kiev, 1979; L and about r and And. Regulation of exchange processes, the lane with fr., M., 1970; JI e of N and N d e r A. Biokhimiya, the lane with English, M., 1976; M and to - M yu solution e y At. A metabolism at the person, the lane with English, M., 1980; Metsler D. E. Biochemistry, the lane with English, t. 1 — 3, M., 1980; H yu with x about l of m E. and Start To. Regulation of metabolism, the lane with English, M., 1977; Pathological physiology, under the editorship of A. D. Ado and JI. M. Ishimova, M., 1973; Pevzner JI. Fundamentals of bio-energetics, the lane with English, M., 1977; The Guide to gerontology, under the editorship of D.F. Chebotaryov, etc., M., 1978; The Guide to clinical endocrinology, under the editorship of V. G. Baranov, JI., 1977; Hochachka P. and With about m of e r and J. The strategy of biochemical adaptation, the lane with English, M., 1977; Sh at r y and D. Ya. N, In I z and the Central Committee and y P. O. and Sidorov K. A. Obesity, JI., 1980; D e r about t M. Maladies du metabolisme, P., 1969; Gray C. H. and. Howorth P. J. Clinical chemical pathology, L., 1977; Handbook of the biology of aging, ed. by of Page E. Finch a. L. Hayflick, N. Y., 1977; H a s with h e n R. u. S with h e u-de D. Abriss der pathologischen Bioche-mie, Jena, 1978; The metabolic basis of inherited disease, ed. by J. B. Stanbury a. o., N. Y. and. lake, 1978; R and r about r about of t S. M of Medizixiische Biochemie, V., 1977; W h i-t e A. o. Principles of biochemistry, N. Y., 1973.
Arshavsky I. A. Sketches on age physiology, page 287, M., 1967; Age physiology, under the editorship of V. N. Nikitin, etc., page 221, 375, J1., 1975; Metsler D. E. Biochemistry, the lane with English, t. 1 — 3, M., 1980; H yu with - the hill E. and Start To. Regulation of metabolism, the lane with English, M., 1977; Larina E. V. Age and exchange of proteins, Kharkiv, 1967; Parina E. V. and Kalimang P. A. Mechanisms of regulation of enzymes in ontogenesis, Kharkiv, 1978; Tabolin V. A., etc. Use of funic concentration of alpha-fetoprotein and immunoglobulin G as indicators of a maturity of premature children, Pediatrics, No. 5, page 44, 1978; Phosphorylation and function, under the editorship of V. S. Ilyin, page of Ill, JI., 1960; Functions of adrenal glands at fruits, newborns and babies, under the editorship of V. A. Ta-bolin, page 43, M., 1975; Harrison J., etc. Human biology, the lane with English, page 390, M., 1979; Weah g e i s s K. Pathobiochemie des Kohlen-hydratstoffwechsels in der Neugelorenen-periode, Ergebn. exp. Med., Bd 30, S. 171, 1978; Cornblath M. Schwartz R. Disorders of carbohydrate metabolism in infancy, Philadelphia, 1966; Handbuch der Gerontologie, hrsg. v. D. P. Chebotarev u. a., Bd 1 — 2, Jena, 1978; Die physiologische Entwicklung, hrsg. v. F. Linneweh, S. 157, B., 1959; Physiology of the perinatal period, ed. by U. Stave, N.Y., 1970; Plenert W. u. Heine W. Normalwerte, Unter-suchungsergebnisse beirn gesunden Menschen unter besonderer Beriicksichtigung des Kin-desalters, B., 1969; White A., Handler P. Smith E. L. Principles of biochemistry, N. Y., 1973.
B. I. Rozengart; P. A. Zarembsky (and.), B. B. Frolkiye (mister.); BB. E. Veltishchev (at children).