Structure and Functions (Magill’s Medical Guide, Sixth Edition)
Metabolism is an ongoing process in living organisms. It is fundamentally concerned with the chemistry of life. An organism’s metabolic rate is the rate at which it consumes the energy it derives from the nutrients that sustain it. Organisms consume energy by converting chemical energy to heat and external work; most of the latter is converted to heat also, as external work, such as walking or moving in any way, overcomes friction. A workable measure of metabolic rate, therefore, is the rate at which an organism produces heat. The food that organisms ingest is measured in Calories, each Calorie being the measure of what is required to raise the temperature of one kilogram of water by one degree Celsius.
Metabolism consists of two essential underlying processes, anabolism and catabolism. In vertebrates, the food ingested is immediately mixed with digestive enzymes in the mouth. These enzymes are produced by the salivary glands. As a ball of food, a bolus, passes through the digestive system, additional enzymes found in the stomach, the pancreas, and the small intestine work upon it, accelerating the digestive process.
Some nonenzymes are also vital to the digestive process. Most notable are hydrochloric acid, which, in the stomach, is a necessary ingredient for the efficient use of the stomach’s pepsin, and bile salts in the small intestine, nonenzymes essential to the digestive process. The action of the...
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Disorders and Diseases (Magill’s Medical Guide, Sixth Edition)
All metabolic disorders stem either from genetic or environmental origins, or from a combination of the two. For example, a person with a predisposition for diabetes, an inherited genetic disorder, may exacerbate this predisposition by indulging in a diet high in fats and carbohydrates, by overindulging in alcoholic beverages, and by engaging in little physical activity.
Environmental factors such as diet and exercise can hasten the onset of a disease that lurks in one’s genes. People with this predisposition who control diet and alcohol consumption and who make strenuous exercise regular parts of their daily activity, however, may forestall the onset of the disease, possibly keeping it at bay for their entire lifetimes.
Significant advances were first made in the 1960’s in tracing the genetic origins of diseases. The discovery that deoxyribonucleic acid (DNA), the molecular basis of heredity, exists in the nucleus of every cell of living organisms was a major biochemical discovery. It has led to vastly increased insights into heredity and into metabolic disorders of genetic origin, certainly the overwhelming majority of all such disorders. Among the many metabolic disorders attributable to inheritance are diabetes, arthritis, gout, phenylketonuria (PKU), Tay-Sachs disease, Niemann-Pick disease, and hemochromatosis.
Microbiologists can detect a number of abnormalities in fetuses by analyzing the...
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
The metabolism was scarcely understood until the 1770’s, when Joseph Priestley discovered oxygen and set other researchers on the path to understanding its role in the biochemical aspects of all life. In the next decade, Antoine-Laurent Lavoisier and Adair Crawford were the first researchers to measure the heat produced by animals and to suggest convincingly that animal catabolism is a form of combustion.
These early, tentative steps toward understanding how organisms derive energy and how they expend it led to further research that, in 1828, resulted in Friedrich Wohler’s synthesis of an organic compound, urea, from inorganic substances, demonstrating that the compounds that living organisms produce can be converted from inorganic to organic through metabolism.
It was not until 1842 that Justus von Liebig categorized foods as falling into three essential types, carbohydrates, lipids, and proteins. He measured the caloric values of nutrients and advanced considerably what was known about nutrition and its role in metabolism. At about the same time, Julius Robert von Mayer and James Joule discovered that motion, heat, and electricity are all forms of the same thing, energy. It was not until the 1890’s, however, that Max Rubner and Wilbur Atwater demonstrated conclusively through empirical data that animals release energy according to thermodynamic and biochemical principles established through studies of...
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Barasi, Mary E. Human Nutrition: A Health Perspective. 2d ed. New York: Oxford University Press, 2003. A text that emphasizes basic nutrition information, its role in metabolism, and the application of this information to health maintenance and disease prevention.
Becker, Kenneth L., et al., eds. Principles and Practice of Endocrinology and Metabolism. 3d ed. Philadelphia: Lippincott Williams and Wilkins, 2001. The treatment of metabolic disorders is extensive and accurate. The contributors are well informed and current in their information.
Devlin, Thomas M., ed. Textbook of Biochemistry: With Clinical Correlations. 6th ed. Hoboken, N.J.: Wiley-Liss, 2006. This college textbook presents considerable information on genetic engineering, hormones, and related topics. Includes chemical structures, diagrams, and references useful to the reader. All descriptions are simple but scholarly.
Edwards, Christopher R., and Dennis W. Lincoln, eds. Recent Advances in Endocrinology and Metabolism. 4th ed. New York: Churchill Livingstone, 1992. Particularly thorough in its treatment of such common metabolic disorders as diabetes, arthritis, and thyroid problems. The contributors also treat the less common metabolic disorders directly and clearly.
Feek, Colin, and Christopher Edwards. Endocrine and Metabolic Disease. New York: Springer, 1988. This comprehensive volume...
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Metabolism (Encyclopedia of Science)
Metabolism refers to all of the chemical reactions that take place within an organism by which complex molecules are broken down to produce energy and by which energy is used to build up complex molecules. An example of a metabolic reaction is the one that takes place when a person eats a spoonful of sugar. Once inside the body, sugar molecules are broken down into simpler molecules with the release of energy. That energy is then used by the body for a variety of purposes, such as keeping the body warm and building up new molecules within the body.
All metabolic reactions can be broken down into one of two general categories: catabolic and anabolic reactions. Catabolism is the process by which large molecules are broken down into smaller ones with the release of energy. Anabolism is the process by which energy is used to build up complex molecules needed by the body to maintain itself and develop.
The process of digestion
One way to understand the process of metabolism is to follow the path of a typical nutrient as it passes through the body. A nutrient is any substance that helps an organism stay alive, remain healthy, and grow. Three large categories of nutrients are carbohydrates, proteins, and fats.
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Metabolism (Encyclopedia of Nursing & Allied Health)
Metabolism refers to the highly integrated network of chemical reactions by which living cells grow and sustain themselves.
The metabolism's network of chemical reactions are composed of two major types of pathways: anabolism and catabolism. Anabolism uses energy stored in the form of adenosine triphosphate (ATP) to build larger molecules from smaller molecules. Catabolic reactions degrade larger molecules in order to produce ATP and raw materials for anabolic reactions.
Together, the body's anabolic and catabolic networks have three major functions:
- to extract energy from nutrients
- to synthesize the building blocks that make up the large molecules of life: proteins, fats, carbohydrates, nucleic acids, and combinations of these substances
- to synthesize and degrade molecules required for special functions in the cell
These reactions are controlled by enzymes, protein catalysts that increase the speed of chemical reactions in the cell without themselves being changed. Each enzyme catalyzes a specific chemical reaction by acting on a specific substrate, or raw material. Each reaction is just one in a sequence of catalytic steps in a metabolic pathway(s). These sequences may be composed of up to 20 enzymes, each one creating a product that becomes the substrate or raw material for the subsequent enzyme. Often, an additional molecule called a coenzyme, is required for the enzyme to function. For example, some coenzymes accept an electron that is released from the substrate during the enzymatic reaction. Most of the water-soluble vitamins of the B complex serve as coenzymes; riboflavin (vitamin B2) for example, is a precursor of the coenzyme flavine adenine dinucleotide, while pantothenate is a component of coenzyme A, an important intermediate metabolite.
The series of products created by the sequential enzymatic steps of anabolism or catabolism are called metabolic intermediates, or metabolites. Each step represents a small change in the molecule, usually the removal, transfer, or addition of a specific atom, molecule or group of atoms that serves as a functional group, such as the amino groups (-NH2) of proteins.
Typically, these metabolic pathways are linear. That is, they begin with a specific substrate and end with a specific product. Some pathways, such as the Krebs cycle, are cyclic. Often, metabolic pathways also have branches that feed into or out of them. The specific sequences of intermediates in the pathways of cell metabolism are called intermediary metabolism.
There are thousands of chemical reactions in the body and many of these pathways are identical in most forms of life.
According to the first law of thermodynamics, in any physical or chemical change, the total amount of energy in the universe remains constant, that is, energy cannot be created or destroyed. Thus, when the energy stored in nutrient molecules is released and captured in the form of ATP, some energy is lost as heat but the total amount of energy is unchanged.
The second law of thermodynamics states that physical and chemical changes proceed in such a direction that useful energy undergoes irreversible degradation into a randomized formntropy. The dissipation of energy during metabolism represents an increase in the randomness, or disorder, of the organism's environment. Because this disorder is irreversible, it provides the driving force and direction to all metabolic enzymatic reactions.
Even in the simplest cells, such as bacteria, there are at least a thousand such reactions. Regardless of the number, all cellular reactions can be classified as one of two types of metabolism: anabolism and catabolism. These reactions, while opposite in nature, are linked through the common bond of energy. Anabolism, or biosynthesis, is the synthetic phase of metabolism during which small building block molecules, or precursors, are built into large molecular components of cells, such as carbohydrates and proteins.
Catabolic reactions are used to capture and save energy from nutrients, as well as to degrade larger molecules into smaller, molecular raw materials for reuse by the cell. The energy is stored in the form of energy-rich ATP, which powers the reactions of anabolism. The useful energy of ATP is stored in the form of a high-energy bond between the second and third phosphate groups of ATP. The cell makes ATP by adding a phosphate group to the molecule adenosine diphosphate (ADP). Therefore, ATP is the major chemical link between the energy-yielding reactions of catabolism, and the energy-requiring reactions of anabolism.
In some cases, energy is also conserved as energyrich hydrogen atoms in the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) in the reduced form of NADPH. The NADPH can then be used as a source of high-energy hydrogen atoms during certain biosynthetic reactions of anabolism.
In addition to the obvious difference in the direction of their metabolic goals, anabolism and catabolism differ in other significant ways. For example, the various degradative pathways of catabolism are convergent. That is, many hundreds of different proteins, polysaccharides and lipids are broken down into relatively few catabolic end products. The hundreds of anabolic pathways, however, are divergent. That is, the cell uses relatively few biosynthetic precursor molecules to synthesize a vast number of different proteins, polysaccharides and lipids.
The opposing pathways of anabolism and catabolism may also use different reaction intermediates or different enzymatic reactions in some of the steps. For example, there are 11 enzymatic steps in the breakdown of glucose into pyruvic acid in the liver. But the liver uses only nine of those same steps in the synthesis of glucose, replacing the other two steps with a different set of enzyme-catalyzed reactions. This occurs because the pathway to degradation of glucose releases energy, while the anabolic process of glucose synthesis requires energy. The two different reactions of anabolism are required to overcome the energy barrier that would otherwise prevent the synthesis of glucose.
Another reason for having slightly different pathways is that the corresponding anabolic and catabolic routes must be independently regulated. Otherwise, if the two phases of metabolism shared the exact pathway (only in reverse) a slowdown in the anabolic pathway would slow catabolism, and vice versa.
In addition to regulating the direction of metabolic pathways, cells, especially those in multicellular organisms, also exert control at three different levels: allosteric enzymes, hormones, and enzyme concentration.
Allosteric enzymes in metabolic pathways change their activity in response to molecules that either stimulate or inhibit their catalytic activity. While the end product of an enzyme cascade is used up, the cascade continues to synthesize that product. The result is a steady-state condition in which the product is used up as it is produced and there is no significant accumulation of product. However, when the product accumulates above the steady-state level for any reason, in excess of the cell's needs, the end product acts as an inhibitor of the first enzyme of the sequence. This process is called allosteric inhibition, and is a type of feedback inhibition.
A classic example of allosteric inhibition is the case of the enzymatic conversion of the amino acids: L-threonine into L-isoleucine by bacteria. The first of five enzymes, threonine dehydratase is inhibited by the end product, isoleucine. This inhibition is very specific, and is accomplished only by isoleucine, which binds to a site on the enzyme molecule called the regulatory, or allosteric, site. This site is different from the active site of the enzyme, which is the site of the catalytic action of the enzyme on the substrate, or molecule being acted on by the enzyme.
Some allosteric enzymes may be stimulated by modulator molecules. These molecules are not the end product of a series of reactions, but rather may be the substrate molecule itself. These enzymes have two or more substrate binding sites, which serve a dual function as both catalytic sites and regulatory sites. Such allosteric enzymes respond to excessive concentrations of substrates that must be removed. Also, some enzymes have two or more modulators with opposite effects and possess their own specific allosteric site. When occupied, one site may speed up the catalytic reaction, while the other may slow it down. ADP and AMP (adenosine monophosphate) stimulate certain metabolic pathway enzymes, for example, while ATP inhibits the same allosteric enzymes.
The activity of allosteric enzymes in one pathway may also be modulated by intermediate or final products from other pathways. Such cross-reaction is an important way in which the rates of different enzyme systems can be coordinated with each other.
Hormonal control of metabolism is regulated by chemical messengers secreted into the blood by different endocrine glands. These messengers, called hormones, travel to other tissues or organs, where they may stimulate or inhibit specific metabolic pathways.
A classic example of hormonal control of metabolism is the hormone adrenaline, which is secreted by the medulla of the adrenal gland and carried by the blood to the liver. In the liver, adrenaline stimulates the breakdown of glycogen to glucose, increasing the blood sugar level. In the skeletal muscles, adrenaline stimulates the breakdown of glycogen to lactate ATP.
Adrenaline exerts its effect by binding to a receptor site on the cell surfaces of liver and muscle cells. From there, adrenaline initiates a series of signals that ultimately causes an inactive form of the enzyme glycogen phosphorylase to become active. This enzyme is the first in a sequence that leads to the breakdown of glycogen to glucose and other products.
Finally, the concentration of the enzymes themselves exert a profound influence on the rate of metabolic activity. For example, the ability of the liver to turn enzymes on and off process called enzyme inductionssures that adequate amounts of needed enzymes are available, while inhibiting the cell from wasting its energy and other resources on making enzymes that are not needed.
For example, in the presence of a high-carbohydrate, low-protein diet, the liver enzymes that degrade amino acids are present in low concentrations. In the presence of a high-protein diet, however, the liver produces increased amounts of enzymes needed for degrading these molecules.
The basis of both anabolic and catabolic pathways is the reactions of reduction and oxidation. Oxidation refers to the combination of an atom or molecule with oxygen, or the loss from it of hydrogen or of one or more electrons. Reduction, the opposite of oxidation, is the gain of one or more electrons by an atom or molecule. The nature of these reactions requires them to occur together; i.e., oxidation always occurs in conjunction with reduction. The term "redox" refers to this coupling of reduction and oxidation.
Redox reactions form the basis of metabolism and are the basis of oxidative phosphorylation, the process by which electrons from organic substances such as glucose are transferred from organic compounds such as glucose to electron carriers (usually coenzymes), and then are passed through a series of different electron carriers to molecules of oxygen molecules. The transfer of electrons in oxidative phosphorylation occurs along the electron transport chain. During this process, called aerobic respiration, energy is released, some of which is used to make ATP from ADP. The major electron carriers are the coenzymes nicotinamide adenine dinucleotide (NADH) or flavin adenine dinucleotide (FADH2). Oxidative phosphorylation is the major source of ATP in aerobic organisms, from bacteria to humans.
Some anaerobic bacteria, however, also carry out respiration, but use other inorganic molecules, such as nitrate (NO3-) or sulfate (SO42-) ions as the final electron acceptors. In this form of respiration, called anaerobic respiration, nitrate is reduced to nitrite ion (NO2-), nitrous oxide (N2O) or nitrogen gas (N2), and sulfate is reduced to form hydrogen sulfide (H2S).
Much of the metabolic activity of cells consists largely of central metabolic pathways that transform large amounts of proteins, fats and carbohydrates. Foremost among these pathways are glycolysis, which can occur in either aerobic or anaerobic conditions, and the Krebs cycle, which is coupled to the electron transport chain, which accepts electrons removed from reduced coenzymes of glycolysis and the Krebs cycle. The final electron acceptor of the chain is usually oxygen, but some bacteria use specific, oxidized ions as the final acceptor in anaerobic conditions.
As vital as these reactions are, there are other metabolic pathways in which the flow of substrates and products is much smaller, yet the products quite important. These pathways constitute secondary metabolism, which produces specialized molecules needed by the cell or by tissues or organs in small quantities. Such molecules may be coenzymes, hormones, nucleotides, toxins, or antibiotics.
The process of extracting energy by the central metabolic pathways that break down fats, polysaccharides and proteins, and conserving it as ATP, occurs in three stages in aerobic organisms. In anaerobic organisms, only one stage is present. In each case, the first step is glycolysis.
Glycolysis is a ubiquitous central pathway of glucose metabolism among living things, from bacteria to plants and humans. The glycolytic series of reactions converts glucose into the molecule pyruvate, with the production of ATP. This pathway is controlled by both the concentration of substrates entering glycolysis as well as by feedback inhibition of the pathway's allosteric enzymes.
Glucose, a hexose (6-carbon) sugar, enters the pathway through phosphorylation of the number six carbon by the enzyme hexokinase. In this reaction, ATP relinquishes one of its phosphates, becoming ADP, while glucose is converted to glucose-6-phosphate. When the need for further oxidation of glucose-6-phosphate by the cell decreases, the concentration of this metabolite increases, as serves as a feedback inhibitor of the allosteric enzyme hexokinase. In the liver, however, glucose-6-phosphate is converted to glycogen, a storage form of glucose. Thus a buildup of glucose-6-phosphate is normal for liver, and feedback inhibition would interfere with this vital pathway. To produce glucose-6-phosphate, the liver must use the enzyme glucokinase, which is not inhibited by an increase in the concentration of glucose-6-phosphate.
In the liver and muscle cells, another enzyme, glycogen phosphorylase, breaks down glycogen into glucose molecules, which then enter glycolysis.
Two other allosteric enzyme regulatory reactions also help to regulate glycolysis: the conversion of fructose 6-phosphate to fructose 1,6-diphosphate by phosphofructokinase and the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase.
The first stage of glycolysis prepares the glucose molecule for the second stage, during which energy is conserved in the form of ATP. As part of the preparatory state, however, two ATP molecules are consumed.
At the fourth step of glycolysis, the doubly phosphorylated molecule (fructose 1,6-diphosphate) is cleaved into two 3-carbon molecules, dihyroxyacetone phosphate and glyceraldehyde 3-phosphate. These 3-carbon molecules are readily converted from one to another, however it is only glyceraldehyde 3-phosphate that undergoes five further changes during the energy conserving stage. In the first step of this second stage, a molecule of the coenzyme NAD+ is reduced to NADH. During oxidative phosphorylation, the NADH will be oxidized, giving up its electrons to the electron transport system.
At steps seven and 10 of glycolysis, ADP is phosphorylated to ATP, using phosphate groups added to the original 6-carbon molecule in the preparatory stage. Since this phosphorylation of ADP occurs by enzymatic removal of a phosphate group from each of two substrates of glycolysis, this process is called substrate level phosphorylation of ADP. It differs markedly from the phosphorylation of ADP that occurs in the more complex oxidative phosphorylation processes in the electron transport chain. Since two three-carbon molecules derived from the original six-carbon hexose undergo this process, two molecules of ATP are formed from glucose during this stage, for a net overall gain of two ATP (two ATP having been used in the preparatory stage).
Aerobic organisms use glycolysis as the first stage in the complete degradation of glucose to carbon dioxide and water. During this process, the pyruvate formed by glycolysis is oxidized to acetyl-Coenzyme A (acetyl-CoA), with the loss of its carboxyl group as carbon dioxide.
The fate of pyruvate formed by glycolysis differs among species, and within the same species depending on the level of oxygen available for further oxidation of the products of glycolysis.
Under aerobic conditions, or in the case of bacteria using a non-oxygen final electron acceptor, acetyl-CoA, enters the Krebs cycle by combining with citric acid. The Krebs cycle continues the oxidation process, extracting electrons as it proceeds. The electrons are carried by coenzymes (NADH and FADH) to the electron transport chain, where the final reactions of oxidation produce ATP.
During these reactions, the acetyl group is oxidized completely to carbon dioxide and water by the citric acid cycle. This final oxidative degradation requires oxygen as the final electron acceptor in the electron transport chain.
Organisms that lack the enzyme systems necessary for oxidative phosphorylation also use glycolysis to produce pyruvate and a small amount of ATP. But pyruvate is then converted into lactate, ethanol or other organic alcohols or acids. This process is called fermentation, and oes not produce more ATP. The NADH produced during the energy-conserving stage of fermentation is used during the synthesis of other molecules. Thus, glycolysis is the major central pathway of glucose catabolism in virtually all organisms.
While the main function of glycolysis is to produce ATP, there are minor catabolic pathways that produce specialized products for cells. One, the pentose phosphate pathway, produces NADPH and the sugar ribose 5-phosphate. NADPH is used to reduce substrates in the synthesis of fatty acids, and ribose 5-phosphate is used in the synthesis of nucleic acids.
Another secondary pathway for glucose in animal tissues produces D-glucuronate, which is important in detoxifying and excreting foreign organic compounds and in synthesizing vitamin C.
Most of the energy conservation achieved by the oxidative phosphorylation of glucose occurs during the Krebs cycle. Pyruvate is first converted to acetyl-CoA, in an enzymatic step that converts one of its carbons into carbon dioxide, and NAD+ is reduced to NADH. Acetyl-CoA enters the 8-step Krebs cycle by combining with the 4-carbon oxaloacetic acid to form the 6-carbon citric acid. During the next seven steps, three molecules of NAD+ and one molecule of FAD+ are reduced, one ATP is formed by substrate level phosphorylation, and two carbons are oxidized to CO2.
The reduced coenzymes produced during conversion of pyruvic acid to acetyl-CoA and the Krebs cycle are oxidized along the electron transport chain. As the electrons released by the coenzymes pass through the stepwise chain of redox reactions, there is a stepwise release of energy that is ultimately used to phosphorylate molecules of ADP to ATP. The energy is converted into a gradient of protons established across the membrane of the bacterial cell or of the organelle of the eucaryotic cells. The energy of the proton flow back into the cell or organelle is used by the enzyme ATP synthetase to phosphorylate ADP molecules.
FADH2 releases its electrons at a lower level along the chain than does NADH. The electrons of the former coenzyme thus pass along fewer electron acceptors than NADH, and this difference is reflected in the number of ATP molecules produced by the sequential transfer of each coenzymes electrons along the chain. The oxidation of each NADH produces three ATP, while the oxidation of FADH2 produces two.
The total number of ATP produced by glycolysis and metabolism is 38, which includes a net of two from glycolysis (substrate level phosphorylation), 30 from the oxidation of 10 NADH molecules, four from oxidation of two FADH2 molecules, and two from substrate level phosphorylation in the Krebs cycle.
In addition to their role in the catabolism of glucose, glycolysis and the Krebs cycle also participate in the breakdown of proteins and fats. Proteins are initially degraded into constituent amino acids, which may be converted to pyruvic acid or acetyl-CoA before being passed into the Krebs cycle; or they may enter the Krebs cycle directly after being converted into one of the metabolites of this metabolic pathway.
Lipids are first hydrolyzed into glycerol and fatty acids, glycerol being converted to the glyceraldehyde 3-phosphate metabolite of glycolysis, while fatty acids are degraded to acetyl-CoA, which then enters the Krebs cycle.
Although metabolic pathways in both single-celled and multicellular organisms have much in common, especially in the case of certain central metabolic pathways, they may occur in different locations.
In the simplest organisms, the prokaryotes, metabolic pathways are not contained in compartments separated by internal membranes. Rather, glycolysis takes place in
the cytosol, while the electron transport chain and lipid synthesis occurs in the cell membrane. Proteins are made on ribosomes in the cytosol.
In eucaryotic cells, glycolysis, gluconeogenesis and fatty acid synthesis takes place in the cytosol, while the Krebs cycle is isolated within mitochondria; glycogen is made in glycogen granules, lipid is synthesized in the endoplasmic reticulum and lysosomes carry on a variety of hydrolytic activities. As in procaryotic cells, ribosomes in the cytosol are the site of protein synthesis.
Role in human health
All reactions of metabolism are part of the overall goal of the organism to maintain its internal order; whether the organism is a single celled protozoan or a human. Organisms maintain this order by removing energy from nutrients or sunlight and returning to their environment an equal amount of energy in a less useful form, mostly heat. This heat becomes dissipated throughout the rest of the organism's environment.
The metabolic pathways discussed oxidize organic matter to produce ATP in order to supply the body with the energy and nutrients it needs for maintenance of body functions, growth, tissue repair, and other processes.
Common diseases and disorders
There are a number of disorders affecting the metabolism. Inborn errors of metabolism (or human hereditary biochemical disorders) have genetic origins; these errors interfere with the synthesis including proteins, carbohydrates, fats enzymes, and many other substances in the body. If the abnormality with synthesis is severe, clinical and chemical consequences may result. Abnormalities in the breakdown, storage, or production of proteins, fats and carbohydrates or in the energy cycles of cells are typically the manifestation of this disorder. Disease and death may result from the absence or excess of normal or abnormal metabolites. Some examples of these inborn errors of metabolism are: galactosemia, phenylketonuria, lactose intolerance, and maple syrup urine disease. Many of these inborn errors of metabolism are untreatable. Some inborn errors of metabolism require dietary and/or nutrient modification depending on the specific metabolic error. Registered dietitians and physicians can assist the patient with the diet modifications needed for each disease.
A disorder with the thyroid gland may have an effect on metabolism. Thyroid hormones have an impact on growth, use of energy, and heat production as well as affecting the use of vitamins, proteins, carbohydrates, fats, electrolytes, and water. They can also alter the effect of other hormones and drugs. Hypothyroidism may result if there is a temporary or permanent reduction in thyroid hormone secretion. Treatment for this condition is most often successful and allows patients to live normally.
Coenzyme coenzyme is required for the enzyme to function.
Enzymesnzymes are protein catalysts that increase the speed of chemical reactions in the cell without themselves being changed.
Glycolysishe major central pathway of glucose catabolism in virtually all organisms. The main function of glycolysis is to produce ATP.
Hormonesormones are messengers that travel to tissues or organs, where they may stimulate or inhibit specific metabolic pathways.
Oxidationxidation refers to the combination of an atom or molecule with oxygen, or the loss from it of hydrogen or of one or more electrons.
Phenylketonuria (PKU) rare hereditary condition in which phenylalanine (an amino acid) is not properly metabolized. PKU may cause severe mental retardation.
Reductioneduction, the opposite of oxidation, is the gain of one or more electrons by an atom or molecule. The nature of these reactions requires them to occur together; i.e., oxidation always occurs in conjunction with reduction. The term "redox" refers to this coupling of reduction and oxidation.
Greenspan, Francis S., and David G. Gardner, eds. Basic & Clinical Endocrinology. 6th ed. Stamford, CT: Appleton & Lange, 2000.
Salway, J. G. Metabolism at a Glance. 2nd ed. Oxford: Blackwell Science Inc., 1999.
Academic Press. Molecular Genetics and Metabolism. San Diego, CA: Harcourt Science and Technology Company. <<a href="http://www.apnet.com/www/journal/gm.htm">http://www.apnet.com/www/journal/gm.htm>.
The Endocrine Society. The Journal of Clinical Endocrinology & Metabolism <<a href="http://jcem.endojournals.org/">http://jcem.endojournals.org/>.
Center for Inherited Disorders of Energy Metabolism, Case Western Reserve University School of Medicine, Cleveland, OH. <<a href="http://www.cwru.edu/2352896/med/CIDEM/cidem.htm">http://www.cwru.edu/2352896/med/CIDEM/cidem.htm>.
Metabolism Foundation, 622 Leatherwood Circle, Edmond, OK 73003. <<a href="http://www.metabolism.net">http://www.metabolism.net>.
Society for Inherited Metabolic Disorders, incorporated through the State of Oregon, non-profit society. <<a href="http://www.simd.org">http://www.simd.org>.
Society for the Study of Inborn Errors of Metabolism, Cardiff, Wales. <<a href="http://www.ssiem.org/uk/ssiemj.html">http://www.ssiem.org/uk/ssiemj.html>.
Crystal Heather Kaczkowski, MSc.
Metabolism (World of Microbiology and Immunology)
Metabolism is the sum total of chemical changes that occur in living organisms and which are fundamental to life. All prokaryotic and eukaryotic cells are metabolically active. The sole exception is viruses, but even viruses require a metabolically active host for their replication.
Metabolism involves the use of compounds. Nutrients from the environment are used in two ways by microorganisms. They can be the building blocks of various components of the microorganism (assimilation or anabolism). Or, nutrients can be degraded to yield energy (dissimilation or catabolism). Some so-called amphibolic biochemical pathways can serve both purposes. The continual processes of breakdown and re-synthesis are in a balance that is referred to as turnover. Metabolism is an open system. That is, there are constant inputs and outputs. A chain of metabolic reactions is said to be in a steady state when the concentration of all intermediates remains constant, despite the net flow of material through the system. That means the concentration of intermediates remains constant, while a product is formed at the expense of the substrate.
Primary metabolism comprises those metabolic processes that are basically similar in all living cells and are necessary for cellular maintenance and survival. They include the fundamental processes of growth (e.g., the synthesis of biopolymers and the macromolecular structures of cells and organelles), energy production (glycolysis and the tricarboxylic acid cycle) and the turnover of cell constituents. Secondary metabolism refers to the production of substances, such as bile pigments from porphyrins in humans, which only occur in certain eukaryotic tissues and are distinct from the primary metabolic pathways.
Metabolic control processes that occur inside cells include regulation of gene expression and metabolic feedback or feed-forward processes. The triggers of differential gene expression may be chemical, physical (e.g., bacterial cell density), or environmental (e.g., light). Differential gene expression is responsible for the regulation, at the molecular level, of differentiation and development, as well as the maintenance of numerous cellular "house-keeping" reactions, which are essential for the day-to-day functioning of a microorganism. In many metabolic pathways, the metabolites (substances produced or consumed by metabolism) themselves can act directly as signals in the control of their own breakdown and synthesis. Feedback control can be negative or positive. Negative feedback results in the inhibition by an end product, of the activity or synthesis of an enzyme or several enzymes in a reaction chain. The inhibition of the synthesis of enzymes is called enzyme repression. Inhibition of the activity of an enzyme by an end product is an allosteric effect and this type of feedback control is well known in many metabolic pathways (e.g., lactose operon). In positive feedback, an endproduct activates an enzyme responsible for its own production.
Many reactions in metabolism are cyclic. A metabolic cycle is a catalytic series of reactions, in which the product of one bimolecular (involving two molecules) reaction is regenerated as follows: A + B C + A. Thus, A acts catalytically and is required only in small amounts and A can be regarded as carrier of B. The catalytic function of A and other members of the metabolic cycle ensure economic conversion of B to C. B is the substrate of the metabolic cycle and C is the product. If intermediates are withdrawn from the metabolic cycle, e.g., for biosynthesis, the stationary concentrations of the metabolic cycle intermediates must be maintained by synthesis. Replenishment of depleted metabolic cycle intermediates is called anaplerosis. Anaplerosis may be served by a single reaction, which converts a common metabolite into an intermediate of the metabolic cycle. An example of this is pyruvate to oxaloacetate reaction in the tricarboxylic acid cycle. Alternatively, it may involve a metabolic sequence of reactions, i.e., an anaplerotic sequence. An example of this is the glycerate pathway which provides phosphoenol pyruvate for anaplerosis of the tricarboxylic acid cycle.
Prokaryotes exhibit a great diversity of metabolic options, even in a single organism. For example, Escherichia coli can produce energy by respiration or fermentation. Respiration can be under aerobic conditions (e.g., using O2 as the final electron acceptor) or anaerobically (e.g., using something other than oxygen as the final electron acceptor). Compounds like lactose or glucose can be used as the only source of carbon. Other bacteria have other metabolic capabilities including the use of sunlight for energy.
Some of these mechanisms are also utilized by eukaryotic cells. In addition, prokaryotes have a number of energy-generating mechanisms that do not exist in eukaryotic cells. Prokaryotic fermentation can be uniquely done via the phosphoketolase and Enter-Doudoroff pathways. Anaerobic respiration is unique to prokaryotes, as is the use of inorganic compounds as energy sources or as carbon sources during bacterial photosynthesis. Archaebacteria possess metabolic pathways that use H2 as the energy source with the production of methane, and a nonphotosynthetic metabolism that can convert light energy into chemical energy.
In bacteria, metabolic processes are coupled to the synthesis of adenosine triphosphate (ATP), the principle fuel source of the cell, through a series of membrane-bound proteins that constituent the electron transport system. The movement of protons from the inside to the outside of the membrane during the operation of the electron transport system can be used to drive many processes in a bacterium, such as the movement of the flagella used to power the bacterium along, and the synthesis of ATP in the process called oxidative phosphorylation.
The fermentative metabolism that is unique to some bacteria is evolutionarily ancient. This is consistent with the early appearance of bacteria on Earth, relative to eukaryotic organisms. But bacteria can also ferment sugars in the same way that brewing yeast (i.e., Saccharomyces cerevesiae ferment sugars to produce ethanol and carbon dioxide. This fermentation, via the so-called Embden Myerhoff pathway, can lead to different ends products in bacteria, such as lactic acid (e.g., Lactobacillus), a mixture of acids (Enterobacteriacaeae, butanediol (e.g., Klebsiella, and propionic acid (e.g., Propionibacterium).
See also Bacterial growth and division; Biochemistry