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Medical Specializations


Radiotherapy => Chemotherapy => Metabolism


Metabolism


INTRODUCTION
Metabolism, inclusive term for the chemical reactions by which the cells of an organism transform energy, maintain their identity, and reproduce. All life forms-from single-celled algae to mammals-are dependent on many hundreds of simultaneous and precisely regulated metabolic reactions to support them from conception through growth and maturity to the final stages of life. Each of these reactions is triggered, controlled, and terminated by specific cell enzymes or catalysts, and each reaction is coordinated with the numerous other reactions throughout the organism.

ANABOLISM AND CATABOLISM
Two metabolic processes are recognized: anabolism and catabolism. Anabolism, or constructive metabolism, is the process of synthesis required for the growth of new cells and the maintenance of all tissues. Catabolism, or destructive metabolism, is a continuous process concerned with the production of the energy required for all external and internal physical activity. Catabolism also involves the maintenance of body temperature and the degradation of complex chemical units into simpler substances that can be removed as waste products from the body through the kidneys, intestines, lungs, and skin.

Anabolic and catabolic reactions follow what are called pathways-that is, they are linked to produce specific, life-essential end products. Biochemists have been able to determine how some of these pathways weave together, but many of the finer intricacies are still only partly explored. Basically, anabolic pathways begin with relatively simple and diffuse chemical components, called intermediates. Taking their energy from enzyme-catalysed reactions, the pathways then build towards specific end products, especially macromolecules in the forms of carbohydrates, proteins, and fats. Using different enzyme sequences and taking the opposite direction, catabolic pathways break down complex macromolecules into smaller chemical compounds for use as relatively simple building blocks.

When anabolism exceeds catabolism, growth or weight gain occurs. When catabolism exceeds anabolism, such as during periods of starvation or disease, weight loss occurs. When the two metabolic processes are balanced, the organism is said to be in a state of dynamic equilibrium.

HOW METABOLISM DERIVES ITS ENERGY
In keeping with the first two laws of thermodynamics, organisms can neither create nor destroy energy but can only transform it from one form to another. Thus, the chlorophyll of plants, at the foundation of the food web, captures energy from sunlight and uses it to power the synthesis of living plant cells from inorganic substances such as carbon dioxide, water, and ammonia. This energy, in the form of high-energy products (carbohydrates, fats, and proteins), is then ingested by herbivores and secondarily by carnivores, providing these animals with their only source of energy and cell-building chemicals.

All living organisms, therefore, ultimately derive their energy from the Sun. On reproducing, each species member-whether green plant, herbivore, or carnivore-passes on specific genetic instructions on how to intercept, transform, and finally release energy back into the environment during its lifespan. Metabolism, from a thermodynamic point of view, embraces the processes by which cells chemically intercept and distribute energy as it continuously passes through the organism.

FOOD AND ENERGY
All organisms depend on energy from food for life. Carbohydrates, fats, and proteins are synthesized in plants during periods of available sunlight and stored in tubers (potatoes) or roots, to be drawn on during periods when new growth calls for large energy expenditure.

Food energy is expressed in Calories or joules. (In energy metabolism this unit usually refers to the large Calorie, or kilocalorie: the amount of heat energy required to raise the temperature of 1 kg of water by 1°C.) Carbohydrates have an average value of 4.1 Calories (17 joules) per gram, proteins have 5.7 Calories (24 joules) per gram, and fats have an average of 9.3 Calories (39 joules) per gram. Organisms rely more heavily on one or another of these foods to suit particular needs. An arctic fox, for example, depends almost entirely on lightweight, high-energy-yielding fats. Seeds, which must be light in weight yet contain large amounts of energy, are likely to contain a high percentage of oils. A sugar maple, however, which leads a fixed existence and has ample storage space in its roots, relies almost entirely on carbohydrates in the form of sucrose.

When foods-especially in the form of carbohydrates and fats-are burned in the animal system, they yield the same Calories per gram as when undergoing rapid combustion in a laboratory calorimeter. Mechanical engines, in fact, yield the same number of calories per gram of fuel as animal systems. Mechanical and animal systems also yield large amounts of heat energy and relatively small amounts of work energy. Animal muscle yields only about one calorie of work for every four given up as heat. In animal systems, however, heat does not go entirely wasted. It is needed (especially by warm-blooded animals) to maintain body temperature and to induce metabolic reactions, which at lower temperatures would take place too slowly to be able to maintain bodily functions.

Although living cells conform to the same laws of energy transformation as machines, they are infinitely more versatile. One unique characteristic of living systems is their ability to consume their own tissues after they have exhausted all other food-energy stores. Another is that instead of radically releasing energy through rapidly combusting compounds, like a car engine, living cells release energy in step-by-step chemical reactions. The energy yielded by one chemical reaction drives other reactions, enabling a gradual release of energy with minimum fatigue to the cells.

USE AND TRANSFER OF ENERGY
The chemical reactions taking place in tissues undergoing both degradation in catabolism and resynthesis in anabolism are either exergonic or endergonic. Exergonic reactions, which occur during catabolism, liberate, or give off, energy from within the system of reacting substances; endergonic reactions, which occur during anabolism, require energy from the outside. Once the substances of an endergonic reaction have absorbed energy, they may form an exergonic reaction. Oxidative reactions set off endergonic reactions within cells. When one chemical reaction drives another, the two are said to be coupled. Metabolism takes place through many such energy-yielding reactions, linking up and forming an intricate, interrelated network within the cell.
Chemical energy is exchanged in all living cells through adenosine triphosphate, or ATP, a compound that contains high-energy phosphate bonds. ATP is used by plants to transfer chemical energy from photosynthetic sources. In transferring energy to other molecules, ATP loses one or two of its phosphate groups, becoming adenosine diphosphate (ADP) or adenosine monophosphate (AMP). Both ADP and AMP can be reconverted to ATP by plants, through photosynthesis, or by animals, through chemical energy.

REGULATION OF METABOLISM
The fact that cells and tissues retain their dynamic equilibrium throughout the life of an organism clearly shows that metabolic processes are under fine control. Cells and entire tissues are constantly dying, yet all the chemical ingredients that replenish and form new cells and their products are supplied by metabolism, striking a nearly perfect balance.

Although much remains to be revealed about metabolic processes, biochemists now agree that regulatory, or rate-limiting, enzymes figure largely in the reactions involved. Affecting metabolic pathways at the earliest steps, each enzyme molecule has a specific, or active, site that matches, or "fits", its particular substrate-the compound with which the enzyme forms a product. The precision with which rate-limiting enzymes and substrates join to set off a particular reaction inhibits reactions from occurring indiscriminately in cells, where so many diverse chemical compounds are in flux. Tiny amounts of a rate-limiting enzyme can cause profound changes in the metabolism of a cell.

Another way in which metabolic pathways are controlled is through negative feedback (see Biofeedback). Thus, once a cell synthesizes the correct balance of a product, such as ATP, the accumulation of that product will inhibit the enzymes that trigger its production.

Metabolism, especially in higher animals, is also regulated by the nervous system, the pancreas, the pituitary gland, and the adrenal gland (See Endocrine System). Hormones, secreted into the bloodstream, reach target tissues, often altering the permeability of cell membranes and thereby altering the amounts of substances that get into and out of cells. Hormones, which also affect plant metabolism, change metabolic pathways by altering the catalytic sites of rate-limiting enzymes.

METABOLISM OF FOODSTUFFS
Although the three major foodstuffs-proteins, carbohydrates, and fats-have different chemical compositions and follow independent biochemical pathways, at a certain stage in metabolic reactions, they all form carbon compounds. These compounds follow the same pattern of oxidative reactions that eventually yield carbon dioxide and water for excretion from the body. Each step involves a number of highly complex and coincident biochemical reactions.

° Proteins
Complex proteins are absorbed from the digestive tract and are broken down into about 20 amino acids needed for cellular anabolism. Amino acids may undergo further chemical change to form such internal secretions as hormones and digestive enzymes. Amino acids in excess of those required to replenish body cells and fluids are catabolized in two steps. The first is deamination, in which the nitrogen-containing part of the molecule is removed and united with carbon and oxygen to form urea, ammonia, and uric acid-the nitrogenous products of protein metabolism. Following deamination, each of the remaining amino acids undergoes further chemical breakdown to form other compounds, which are then still further catabolized, often by pathways common to those of similar products from the catabolism of carbohydrates and fat. The end products of these protein portions are carbon dioxide and water.

° Carbohydrates
Carbohydrates are absorbed from the digestive tract as simple sugars, chiefly glucose. Maintained in the blood at an approximately constant level, glucose is readily catabolized to satisfy the need of the body for energy. In this process, the glucose molecule breaks down into carbon compounds that are readily oxidized to carbon dioxide and water and then excreted. If not used immediately for energy, glucose is converted to glycogen (see Starch) and stored in the liver and muscles. When these reserves are filled, glucose is converted to fat and deposited in adipose tissue. See also Sugar Metabolism.

° Fats
In digestion, fats are hydrolysed or decomposed into their component glycerine and fatty acids. These are then synthesized to neutral fats, cholesterol compounds, and phospholipids-fats, chemically united with phosphorus, that circulate in the blood. Fat may be synthesized into body structure or stored in the tissues for withdrawal when needed. Like glucose, it is then catabolized to carbon substances that are broken down into carbon dioxide and water.

° Vitamins
Vitamins are organic compounds essential to enhancement of the metabolism of amino acids, carbohydrates, and fats in living organisms. Some organisms, notably green plants, synthesize vitamins, often in quantities greater than the organisms require. With few exceptions, animals cannot synthesize these substances and must obtain them in their food. See Human Nutrition.

INBORN METABOLIC ERRORS
If an enzyme is lacking because of some hereditary defect, the chemical transformation in which it would participate is blocked. As a result, cell products fail to be synthesized or catabolized, too much of a metabolic product accumulates, causing injury to tissues, or intracellular materials fail to cross cell membranes.

Although the effects of some metabolic errors are manifested in early infancy, others may appear only in adulthood. Some inborn errors may be fatal, some may have no apparent harmful effects, and some may persist. A result of error in amino acid metabolism is phenylketonuria (PKU). This occurs in infants when metabolism of the amino acid phenylalanine is blocked; the accumulated metabolic products may cause brain damage. In carbohydrate metabolism, one error results in galactosaemia, in which the enzyme required to convert galactose to glucose is absent. The consequent inability to metabolize milk sugar results in the accumulation of galactose in the blood, sometimes with damage to the brain and liver and the development of cataracts and mental retardation.

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