Meaning of METABOLISM in English
the sum of all the chemical reactions that take place within every single cell of a living organism, providing energy for vital processes and synthesizing new organic material. Metabolic reactions are of two sorts. Some are anabolic reactions, which use energy to build complex molecules from simple molecules. The others are catabolic reactions, which make chemical energy available in the course of breaking down complex molecules into simpler molecules. In order to carry on its life processes, every organism takes from its environment free, or useful, energy, i.e., energy that is capable of performing work in the conditions of uniform temperature and pressure which characterize the interior of a cell. The organism eventually returns to its environment an equivalent amount of energy, much of it in the biologically unusable form of heat. All the energy used by living organisms derives ultimately from the Sun. Photosynthetic plants use solar energy directly to synthesize organic compounds from inorganic constituents, e.g., carbon dioxide, water, and ammonia. By digesting photosynthetic organisms (or organisms that have digested photosynthetic organisms), nonphotosynthetic organisms obtain nutrientsmostly proteins, carbohydrates, and lipidsthat serve them both as indirect sources of solar energy and as materials from which to synthesize their organic constituents. In all organisms, the cellular reactions involved in metabolism make use of a particular energy-transferring compoundadenosine triphosphate (ATP). ATP releases energy when it is reduced; i.e., when it drops its phosphate groups to become first adenosine diphosphate (ADP) and then adenosine monophosphate (AMP). As ATP is reconstructed from these intermediate compounds, energy is stored. During anabolic reactions, which require energy, ATP is reduced; during catabolic reactions, which yield energy, ATP is synthesized. Every cellular chemical reaction is mediated by a specific enzyme (a protein that initiates and provides a site for a reaction between substances, without itself being chemically changed in the reaction). By their availability or unavailability as catalysts for chemical reactions, these enzymes regulate anabolism and catabolism. The first phase of the liberation of chemical energy from food occurs mainly in the digestive tract in animals and is mostly a preliminary to catabolism; large food molecules are broken down into a number of relatively smaller molecules. Thus, proteins are broken down into the 20 or so amino acids of which they are composed, carbohydrates are broken down into simple sugars, and lipids into fatty acids and glycerols. The products of the first phase enter into the cells, where they are incompletely oxidized (by removal of hydrogen atoms or electrons). This incomplete oxidation constitutes the second phase of energy liberation, the key products of which are three carbon compoundsacetyl coenzyme A, oxaloacetate, and -oxoglutarate. The details of the third and final phase of energy release from food were first elucidated by Sir Hans Krebs in 1937; in it, the products of the second phase combine and pass through a sequence of reactions (called the Krebs cycle, or tricarboxylic acid cycle) that results ultimately in the re-formation of oxaloacetate and the production of two molecules of carbon dioxide (terminal respiration). Hydrogen atoms removed from intermediate products of this cycle are passed along a chain of carriers, eventually combining with oxygen to form water. Energy is released as the hydrogen atoms pass down the carrier chain; this energy is used to synthesize many molecules of ATP. This method of ATP synthesis, which requires oxygen, is called oxidative phosphorylation. Yeasts and certain other microorganisms do not produce ATP by oxidative phosphorylation; instead, they use intermediate products of the second phase of energy liberation as hydrogen acceptors. The end products of this process, which is called fermentation, are ethyl alcohol or lactic acid. Fermentation does not require oxygen, but it results in the synthesis of substantially less ATP than is achieved via oxidative phosphorylation. Fermentation also occurs in animal muscle cells when energy needs outstrip the cell's supply of oxygen. The catabolic process begins with proteins, carbohydrates, and lipids and has as its rather indefinite end products the interconvertible intermediary compounds of the Krebs cycle. Anabolism begins with intermediate compounds and has as its end products the proteins, carbohydrates, lipids, and other large molecules that make up the tissues of the organism. Although certain chemical reactions and intermediary products (e.g., acetyl coenzyme A) occur in both processes, the catabolism and anabolism of a specific compound are not achieved through reversals of the same chemical pathway. Control over the rate of metabolic processes results from the greater or lesser production of the enzymes involved. Fine control results from the property of some of these enzymes (called pacemaker enzymes) whereby interaction with certain molecules other than their substrates (the substances they catalyze) causes them to modify their catalytic activity. The molecules that cause these modulations interact with the pacemaker enzymes at sites other than their active sites (those where they react with their substrates). These interfering molecules may be ATP or other products of the metabolic process to which the enzyme contributes, or they may be substances involved in another metabolic process. In any case, their availability to interact with the enzyme is an indication of the degree to which the reaction catalyzed by the enzyme may at a given moment be necessary to or superfluous in maintaining the metabolic balance of the organism. Information about metabolic pathways is obtained in various ways. Organisms whose metabolisms are unbalanced (through either stress or disease) may accumulate abnormal quantities of particular metabolites (chemical substances involved in metabolism), a situation that will often be indicative of metabolic processes within the organism. Information as to metabolic pathways may also be obtained by feeding an organism nutrient compounds containing isotopes and then monitoring the isotopic atoms as they pass through and out of the organism. It is through the use of isotopes that rates of degeneration and reconstruction of the various tissues in the human body are known (e.g., proteins in liver cells are replaced every five days, though the liver cells themselves last several months; proteins in muscle and brain tissue last much longer than do liver proteins). Important information linking enzymesubstrate pairs has been gained by the use of laboratory-bred mutants; these animals, genetically unable to synthesize particular metabolic enzymes, accumulate the substrate of that enzyme in their cells. Metabolic diseases arise from nutritional deficiencies, especially of vitamins or proteins; in connection with diseases of the endocrine system, the liver, or the kidneys; or as a result of genetic defects. the sum of the chemical reactions that take place within each cell of a living organism and that provide energy for vital processes and for synthesizing new organic material. Living organisms are unique in that they can extract energy from their environments and use it to carry out activities such as movement, growth and development, and reproduction. But how do living organismsor, their cellsextract energy from their environments, and how do cells use this energy to synthesize and assemble the components from which the cells are made? The answers to these questions lie in the enzyme-mediated chemical reactions that take place in living matter (metabolism). Hundreds of coordinated, multistep reactions, fueled by energy obtained from nutrients and/or solar energy, ultimately convert readily available materials into the molecules required for growth and maintenance. The physical and chemical properties of the components of living things dealt with in this article are found in the articles carbohydrate; cell; hormone; lipid; photosynthesis; and protein. Additional reading General works Albert L. Lehninger, Principles of Biochemistry (1982); Lubert Stryer, Biochemistry, 2nd ed. (1981); Earlene Brown Cunningham, Biochemistry: Mechanisms of Metabolism (1978); Jay Tepperman and Helen M. Tepperman, Metabolic and Endocrine Physiology: An Introductory Text, 5th ed. (1987); S. Dagley and Donald E. Nicholson, An Introduction to Metabolic Pathways (1970). Cell metabolism James Darnell, Harvey Lodish, and David Baltimore, Molecular Cell Biology (1986); T.A.V. Subramanian (ed.), Cell Metabolism, Growth and Environment, 2 vol. (1986); W. Bartley, H.L. Kornberg, and J.R. Quayle (eds.), Essays in Cell Metabolism (1970); J. Frank Henderson and A.R.P. Paterson, Nucleotide Metabolism: An Introduction (1973); David A. Bender, Amino Acid Metabolism, 2nd ed. (1985). Regulation of metabolism Daniel E. Atkinson, Cellular Energy Metabolism and Its Regulation (1977); E.A. Newsholme and C. Start, Regulation in Metabolism (1977); Ronald G. Thurman, Frederick C. Kauffman, and Kurt Jungermann (eds.), Regulation of Hepatic Metabolism (1986); and Charles Zapsalis and R. Anderle Beck, Food Chemistry and Nutritional Biochemistry (1985). Sir Hans Kornberg Regulation of metabolism Fine control The flux of nutrients along each metabolic pathway is governed chiefly by two factors: (1) the availability of substrates on which pacemaker, or key, enzymes of the pathway can act and (2) the intracellular levels of specific metabolites that affect the reaction rates of pacemaker enzymes. Key enzymes are usually complex proteins that, in addition to the site at which the catalytic process occurs (i.e., the active site), contain sites to which the regulatory metabolites bind. Interactions with the appropriate molecules at these regulatory sites cause changes in the shape of the enzyme molecule. Such changes may either facilitate or hinder the changes that occur at the active site. The rate of the enzymatic reaction is thus speeded up or slowed down by the presence of a regulatory metabolite. In many cases, the specific small molecules that bind to the regulatory sites have no obvious structural similarity to the substrates of the enzymes; these small molecules are therefore termed allosteric effectors, and the regulatory sites are termed allosteric sites. Allosteric effectors may be formed by enzyme-catalyzed reactions in the same pathway in which the enzyme regulated by the effectors functions. In this case a rise in the level of the allosteric effector would affect the flux of nutrients along that pathway in a manner analogous to the feedback phenomena of homeostatic processes. Such effectors may also be formed by enzymatic reactions in apparently unrelated pathways. In this instance the rate at which one metabolic pathway operates would be profoundly affected by the rate of nutrient flux along another. It is this situation that, to a large extent, governs the sensitive and immediately responsive coordination of the many metabolic routes in the cell. End-product inhibition Figure 10: Family relationships in amino-acid biosyntheses. Components of proteins are underlined. Figure 12: Fine control of the enzymes of the aspartate family in E. coli (see A biosynthetic pathway is usually controlled by an allosteric effector produced as the end product of that pathway, and the pacemaker enzyme on which the effector acts usually catalyzes the first step that uniquely leads to the end product. This phenomenon, called end-product inhibition, is illustrated by the multienzyme, branched pathway for the formation from oxaloacetate of the aspartate family of amino acids (Figure 10). The system of interlocking controls is described in greater detail in Figure 12. As mentioned previously in this article, only plants and microorganisms can synthesize many of these amino acids, most animals requiring such amino acids to be supplied preformed in their diets. Figure 12: Fine control of the enzymes of the aspartate family in E. coli (see Figure 12: Fine control of the enzymes of the aspartate family in E. coli (see Figure 12 shows that there are a number of pacemaker enzymes in the biosynthetic route for the aspartate family of amino acids, most of which are uniquely involved in the formation of one product. Each of the enzymes functions after a branch point in the pathway, and all are inhibited specifically by the end product that emerges from the branch point. It is not difficult to visualize from Figure 12 how the supplies of lysine, methionine, and isoleucine required by a cell can be independently regulated. Threonine, however, is both an amino acid essential for protein synthesis and a precursor of isoleucine. If the rate of synthesis of threonine from aspartate were regulated as are the rates of lysine, methionine, and isoleucine, an imbalance in the supply of isoleucine might result. This risk is overcome in E. coli by the existence of three different aspartokinase enzymes, all of which catalyze the first step common to the production of all the products derived from aspartate. Each has a different regulatory effector molecule. Thus, one type of aspartokinase is inhibited by lysine, a second by threonine. The third kinase is not inhibited by any naturally occurring amino acid, but its rate of synthesis (see below) is controlled by the concentration of methionine within the cell. The triple control mechanism resulting from the three different aspartokinases ensures that the accumulation of one amino acid does not shut off the supply of aspartyl phosphate necessary for the synthesis of the others. Another example of control through end-product inhibition also illustrates the manner in which the operation of two biosynthetic pathways may be coordinated. Both DNA and the various types of RNA are assembled from purine and pyrimidine nucleotides (see above The synthesis of macromolecules: Nucleic acids and proteins); these in turn are built up from intermediates of central metabolic pathways (see above The synthesis of building blocks: Mononucleotides). The first step in the synthesis of pyrimidine nucleotides is that catalyzed by aspartate carbamoyltransferase . This step initiates a sequence of reactions that leads to the formation of pyrimidine nucleotides such as UTP and CTP . Studies of aspartate carbamoyltransferase have revealed that the affinity of this enzyme for its substrate (aspartate) is markedly decreased by the presence of CTP. This effect can be overcome by the addition of ATP, a purine nucleotide. The enzyme can be dissociated into two subunits: one contains the enzymatic activity and (in the dissociated form) does not bind CTP; the other binds CTP but has no catalytic activity. Apart from providing physical evidence that pacemaker enzymes contain distinct catalytic and regulatory sites, the interaction of aspartate carbamoyltransferase with the different nucleotides provides an explanation for the control of the supply of nucleic acid precursors. If a cell contains sufficient pyrimidine nucleotides (e.g., UTP), aspartate carbamoyltransferase, the first enzyme of pyrimidine biosynthesis, is inhibited. If, however, the cell contains high levels of purine nucleotides (e.g., ATP), as required for the formation of nucleic acids, the inhibition of aspartate carbamoyltransferase is relieved, and pyrimidines are formed. The biosynthesis of cell components The nature of biosynthesis The stages of biosynthesis The biosynthesis of cell components (anabolism) may be regarded as occurring in two main stages. In the first, intermediate compounds of the central routes of metabolism are diverted from further catabolism and are channeled into pathways that usually lead to the formation of the relatively small molecules that serve as the building blocks, or precursors, of macromolecules. In the second stage of biosynthesis, the building blocks are combined to yield the macromoleculesproteins, nucleic acids, lipids, and polysaccharidesthat make up the bulk of tissues and cellular components. In organisms with the appropriate genetic capability, for example, all of the amino acids can be synthesized from ammonia and intermediates of the main routes of carbohydrate fragmentation and oxidation. Such intermediates act also as precursors for the purines, the pyrimidines, and the pentose sugars that constitute DNA and for a number of types of RNA. The assembly of proteins necessitates the precise combination of specific amino acids in a highly ordered and controlled manner; this in turn involves the copying, or transcription, into RNA of specific parts of DNA (see below The synthesis of macromolecules: Nucleic acids and proteins). The first stage of biosynthesis thus requires the specificity normally required for the efficient functioning of sequences of enzyme-catalyzed reactions. The second stage also involvesdirectly for protein and nucleic acid synthesis, less directly for the synthesis of other macromoleculesthe maintenance and expression of the biological information that specifies the identity of the cell, the tissue, and the organism. Utilization of ATP The two stages of biosynthesisthe formation of building blocks and their specific assembly into macromoleculesare energy-consuming processes and thus require ATP. Although the ATP is derived from catabolism, catabolism does not drive biosynthesis. As explained in the first section of this article, the occurrence of chemical reactions in the living cell is accompanied by a net decrease in free energy. Although biological growth and development result in the creation of ordered systems from less ordered ones and of complex systems from simpler ones, these events must occur at the expense of energy-yielding reactions. The overall coupled reactions are, on balance, still accompanied by a decrease in free energy and are thus essentially irreversible in the direction of biosynthesis. The total energy released from ATP, for example, is usually much greater than is needed for a particular biosynthetic step; thus, many of the reactions involved in biosynthesis release inorganic pyrophosphate (PPi) rather than phosphate (Pi) from ATP, and hence yield AMP rather than ADP. Since inorganic pyrophosphate readily undergoes virtually irreversible hydrolysis to two equivalents of inorganic phosphate (see ), the creation of a new bond in the product of synthesis may be accompanied by the breaking of two high-energy bonds of ATPalthough, in theory, one might have sufficed. The efficient utilization for anabolic processes of ATP and some intermediate compound formed during a catabolic reaction requires the cell to have simultaneously a milieu favourable for both ATP generation and consumption. Catabolism occurs readily only if sufficient ADP is available; hence, the concentration of ATP is low. On the other hand, biosynthesis requires a high level of ATP and consequently low levels of ADP and AMP. Suitable conditions for the simultaneous function of both processes are met in two ways. Biosynthetic reactions often take place in compartments within the cell different from those in which catabolism occurs; there is thus a physical separation of energy-requiring and energy-yielding processes. Furthermore, biosynthetic reactions are regulated independently of the mechanisms by which catabolism is controlled. Such independent control is made possible by the fact that catabolic and anabolic pathways are not identical; the pacemaker, or key, enzyme that controls the overall rate of a catabolic route usually does not play any role in the biosynthetic pathway of a compound. Similarly, the pacemaker enzymes of biosynthesis are not involved in catabolism. As discussed below (see Regulation of metabolism: Fine control: Energy state of the cell), catabolic pathways are often regulated by the relative amounts of ATP, ADP, and AMP in the cellular compartment in which the pacemaker enzymes are located; in general, ATP inhibits and ADP (or AMP) stimulates such enzymes. In contrast, many biosynthetic routes are regulated by the concentration of the end products of particular anabolic processes, so that the cell synthesizes only as much of these building blocks as it needs. The combustion of food materials Although the pathways for fragmentation of food materials effect the conversion of a large variety of relatively complex starting materials into only a few simpler intermediates of central metabolic routesmainly pyruvate, acetyl coenzyme A, and a few intermediates of the TCA cycletheir operation releases but a fraction of the energy contained in the materials. The reason is that, in the fermentation process, catabolic intermediates serve also as the terminal acceptors of the reducing equivalents (hydrogen atoms or electrons) that are removed during the oxidation of food; the end products thus may be at the same oxidation level and may contain equivalent numbers of carbon, hydrogen, and oxygen atoms, as the material that was catabolized by a fermentative route. The necessity for pyruvate, for example, to act as hydrogen acceptor in the fermentation of glucose to lactate (see reactions [1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, 11]) results in the conservation of all the component atoms of the glucose molecule in the form of lactate. The consequent release of energy as ATP (in steps and ) is thus small. A more favourable situation arises if the reducing equivalents formed by oxidation of nutrients can be passed on to an inorganic acceptor such as oxygen. In this case, the products of fermentation need not act as hydrogen sinks, in which the energy in the molecule is lost when they leave the cell; instead, the products of fermentation can be degraded further, during phase III of catabolism, and all the usable chemical energy of the nutrient can be transformed into ATP. This section describes the manner in which the products obtained by the fragmentation of nutrients are oxidized (i.e., the manner in which hydrogen atoms or electrons are removed from them) and the manner in which these reducing equivalents react with oxygen, with concomitant formation of ATP. The oxidation of molecular fragments The oxidation of pyruvate The oxidation of pyruvate involves the concerted action of several enzymes and coenzymes collectively called the pyruvate dehydrogenase complex; i.e., a multienzyme complex in which the substrates are passed consecutively from one enzyme to the next, and the product of the reaction catalyzed by the first enzyme immediately becomes the substrate for the second enzyme in the complex. The overall reaction is the formation of acetyl coenzyme A and carbon dioxide from pyruvate, with concomitant liberation of two reducing equivalents in the form of NADH + H+. The individual reactions that result in the formation of these end products are as follows. Pyruvate first reacts with the coenzyme of pyruvic acid decarboxylase (enzyme 1), thiamine pyrophosphate (TPP); in addition to carbon dioxide a hydroxyethylTPPenzyme complex (active acetaldehyde) is formed . Thiamine is vitamin B1; the biological role of TPP was first revealed by the inability of vitamin B1-deficient animals to oxidize pyruvate. The hydroxyethyl moiety formed in is immediately transferred to one of the two sulfur atoms (S) of the coenzyme (6,8-dithio-n-octanoate or lipS2) of the second enzyme in the complex, dihydrolipoyl transacetylase (enzyme 2). The hydroxyethyl group attaches to lipS2 at one of its sulfur atoms, as shown in ; the result is that coenzyme lipS2 is reduced and the hydroxyethyl moiety is oxidized. The acetyl group (CH3C=O) then is transferred to the sulfhydryl (-SH) group of coenzyme A, thereby completing the oxidation of pyruvate (reaction ). The coenzyme lipS2 that accepted the hydroxyethyl moiety in step of the sequence, now reduced, must be reoxidized before another molecule of pyruvate can be oxidized. The reoxidation of the coenzyme is achieved by the enzyme-catalyzed transfer of two reducing equivalents initially to the coenzyme flavin adenine dinucleotide (FAD) and thence to the NAD+ that is the first carrier in the so-called electron transport chain. The passage of two such reducing equivalents from reduced NAD+ to oxygen is accompanied by the formation of three molecules of ATP (see Biological energy transduction). The overall reaction may be written as shown in , in which pyruvate reacts with coenzyme A in the presence of TPP and lipS2 to form acetyl coenzyme A and carbon dioxide, and to liberate two hydrogen atoms (in the form of NADH + H+) that can subsequently yield energy by the reduction of oxygen to water. The lipS2 reduced during this process is reoxidized in the presence of the enzyme lipoyl dehydrogenase, with the concomitant reduction of NAD+. The fragmentation of complex molecules Food materials must undergo oxidation in order to yield biologically useful energy. Oxidation does not necessarily involve oxygen, although it must involve the transfer of electrons from a donor molecule to a suitable acceptor molecule; the donor is thus oxidized and the recipient reduced. Many microorganisms either must live in the absence of oxygen (i.e., are obligate anaerobes) or can live in its presence or its absence (i.e., are facultative anaerobes). If no oxygen is available, the catabolism of food materials is effected via fermentations, in which the final acceptor of the electrons removed from the nutrient is some organic molecule, usually generated during the fermentation process. There is no net oxidation of the food molecule in this type of catabolism; that is, the overall oxidation state of the fermentation products is the same as that of the starting material. Organisms that can use oxygen as a final electron acceptor also use many of the steps in the fermentation pathways in which food molecules are broken down to smaller fragments; these fragments, instead of serving as electron acceptors, are fed into the TCA cycle, the pathway of terminal respiration. In this cycle all of the hydrogen atoms (H) or electrons (e-) are removed from the fragments and are channeled through a series of electron carriers, ultimately to react with oxygen (O; see below Energy conservation). All carbon atoms are eliminated as carbon dioxide (CO2) in this process. The sequence of reactions involved in the catabolism of food materials may thus be conveniently considered in terms of an initial fragmentation (fermentation), followed by a combustion (respiration) process. The catabolism of glucose Glycolysis The transformation of glucose. Quantitatively, the most important source of energy for cellular processes is the six-carbon sugar glucose (C6H12O6). Two structures of glucose are shown in Figure 3, in which the carbon atoms are numbered. (See carbohydrate for a discussion of the chemical nature of glucose and other carbohydrates.) Glucose is made available to animals through the hydrolysis of polysaccharides, such as glycogen and starch, the process being catalyzed by digestive enzymes. In animals, the sugar thus set free passes from the gut into the bloodstream and from there into the cells of the liver and other tissues. In microorganisms, of course, no such specialized tissues are involved. The fermentative phase of glucose catabolism (glycolysis) involves several enzymes; the action of each is summarized below. In living cells many of the compounds that take part in metabolism exist as negatively charged moieties, or anions, and are named as such in most of this article; e.g., pyruvate, oxaloacetate. In order to obtain a net yield of ATP from the catabolism of glucose, it is first necessary to invest ATP. During step the alcohol group at position 6 of the glucose molecule readily reacts with the terminal phosphate group of ATP, forming glucose 6-phosphate and ADP. For convenience, the phosphoryl group (PO32-) is represented by . Because the decrease in free energy is so large, this reaction is virtually irreversible under physiological conditions. In animals, this phosphorylation of glucose, which yields glucose 6-phosphate, is catalyzed by two different enzymes. In most cells a hexokinase with a high affinity for glucosei.e., only small amounts of glucose are necessary for enzymatic activityeffects the reaction. In addition, the liver contains a glucokinase, which requires a much greater concentration of glucose before it reacts. Glucokinase functions only in emergencies, when the concentration of glucose in the blood rises to abnormally high levels. Certain facultative anaerobic bacteria also contain hexokinases but apparently do not use them to phosphorylate glucose. In such cells, external glucose can be utilized only if it is first phosphorylated to glucose 6-phosphate via a system linked to the cell membrane that involves a compound called phosphoenolpyruvate (formed in step of glycolysis), which serves as an obligatory donor of the phosphate group; i.e., ATP cannot serve as the phosphate donor in the reaction. The reaction in which glucose 6-phosphate is changed to fructose 6-phosphate is catalyzed by phosphoglucoisomerase . In the reaction, a secondary alcohol group (-CHOH) at the second carbon atom is oxidized to a keto-group (i.e., -C=O), and the aldehyde group (-CHO) at the first carbon atom is reduced to a primary alcohol group (-CH2OH). Reaction is readily reversible, as is indicated by the double arrows. The formation of the alcohol group at the first carbon atom permits the repetition of the reaction effected in step ; that is, a second molecule of ATP is invested. The product is fructose 1,6-diphosphate . Again, as in the hexokinase reaction, the decrease in free energy of the reaction, which is catalyzed by phosphofructokinase, is sufficiently large to make this reaction virtually irreversible under physiological conditions; ADP is also a product. The first three steps of glycolysis have thus transformed an asymmetrical sugar molecule, glucose, into a symmetrical form, fructose 1,6-diphosphate, containing a phosphoryl group at each end; the molecule next is split into two smaller fragments that are interconvertible. This elegant simplification is achieved via steps and , which are described below.
Britannica English vocabulary. Английский словарь Британика. 2012