Structure and Functions
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 digestive apparatus results in catabolism, or the breaking down of the components of food, notably lipids, carbohydrates, and proteins, into small molecules used to build and repair cells. Such molecules, through absorption, traverse the wall of the small intestine to enter the blood or the lymph so that they can be distributed throughout the body to meet its immediate requirements.
Amino acids break down protein, permitting it to enter the bloodstream, whereas glucose and other enzymes act to break down the large carbohydrates into small molecules that are absorbed into the bloodstream. After they are catabolized into smaller molecules, the lipids or fats, unlike proteins and carbohydrates, enter the lymphatic system rather than the bloodstream, which they can enter only after they have passed through the lymphatic system.
Organisms typically cannot digest all the types of nutrients they ingest. Most vertebrates, for example, are incapable of digesting cellulose, the major carbohydrate component of most plants. This material, therefore, simply passes through the digestive system and is excreted. Fiber, which passes through the digestive tract essentially undigested, performs a valuable function in keeping the colon clear and, over the long term, in preventing colon cancer.
A remarkably complex biochemical process occurs when the circulatory system delivers its absorbed sugars, lipids, and amino acids to the parts of the body where they are needed to build new cells and repair existing cells. Sometimes, this process requires the conversion of sugar molecules to fat molecules or animo acids. For a cell to construct a protein, it must connect in a specific, complex order the many animo acid molecules that the process requires. While some of the requisite amino acids result directly from ingesting nutrients, others are not available in this way and must be obtained through the synthesis of sugar molecules.
Molecules that an organism need for survival but that it cannot manufacture itself are obtained through ingestion. Such molecules are called essential nutrients. It takes twenty different kinds of amino acids, for example, to manufacture protein, but the body is capable of producing only half of these. Because green plants can synthesize all twenty forms of amino acids, they are a major and ready source of the essential nutrients required to sustain life.
Also, as part of a nutritional chain, one can note that although neither humans nor chickens can synthesize valine, a vital amino acid, chickens obtain valine by eating grain that is rich in it. Humans, in turn, eat chickens, through which they obtain valine. This amino acid is also available to humans through the green vegetables they eat.
The food that organisms ingest is used both to provide the necessary building blocks for the synthesis of membranes, enzymes, and other parts of cells and to provide energy. If the nutrients ingested are greater than the body’s requirements for such synthesis and for the production of energy, then food molecules may be husbanded for future use in storage compounds within the organism. The excess stored in this way is usually in the form of lipids. In humans, such excesses are stored essentially around the abdomen and buttocks, where they can accumulate in considerable quantity.
If a human’s food supply is severely reduced or completely cut off, the body draws on these reserves, using the stored fat cells until they have been completely depleted. Afterward, nutrients, mostly proteins, will be drawn from muscle mass, the sudden reduction of which can quickly eventuate in death.
The survival of organisms is usually dependent upon the work that they perform. Energy to carry out this work is derived through the splitting of the chemical bonds of
adenosine triphosphate (ATP) and the splitting of the bonds of food molecules. Highly sophisticated and refined series of biochemical reactions called cellular respiration and aerobic catabolism permit most animals to transfer energy from the chemical bonds of nutrient molecules to the bonds of ATP.
Every cell in the body has the enzymes and cellular equipment to carry out aerobic catabolism and to manufacture its own ATP. Oxygen, carried through the blood, is the essential ingredient in aerobic catabolism, which results in the oxidization of nutrient molecules and their being broken up into small molecules composed largely of carbon dioxide and water. In this process, energy is released, some of it lost as heat and some of it conserved in the bonds of ATP.
As amino acids, lipids, and carbohydrates are catabolized in humans, the lipids and carbohydrates are used by the muscles, whereas the brain gains its energy almost exclusively through the glucose that catabolized carbohydrates produce. Excess amino acids are converted by the liver and, to a smaller extent, by the kidneys to carbohydrates or lipids.
In a process called anaerobic glycolysis, which involves the creation of ATP without the presence of oxygen, energy is produced by converting glucose or glycogen into lactic acid. The body cannot excrete lactic acid, thereby making impossible its accumulation in its original form in the body. Lactic acid is released into the bloodstream after exercise and, subjected to oxygen, is metabolized by the liver and either converted to glucose or oxidized aerobically in order to release additional energy.
As vertebrates age, their metabolic rate often decreases. In humans, a decreased metabolic rate, reduced activity in old age, and a failure to reduce caloric intake can result in substantial weight gain. Therefore, as humans age, their physicians usually encourage them to engage in physical activity and to reduce the overall number of calories that they consume. Physical activity generally helps to sustain the basal metabolism at levels higher than those found among the sedentary.
Disorders and Diseases
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 1960s 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 amniotic fluid that surrounds them in the womb. This process, known as amniocentesis, can identify more than twenty inherited metabolic disorders before an infant is born. Genetic manipulation in utero can alter some metabolic disorders, thereby bypassing or modifying faulty or abnormal genes. The genes of a person carrying a predisposition for a metabolic defect usually do not carry the information required for the synthesizing of a particular protein, usually an enzyme. This deficiency inhibits catalytic activity and blocks a metabolic pathway, resulting in a genetic abnormality.
In a minority of cases, the protein serves a role in transport or acts as a cell-surface receptor. Whatever role the protein in question serves, a delicate balance exists within the cells. When this balance is disturbed, metabolic problems ensue. For example, a gene may be responsible for producing an enzyme that converts one substance to another substance. If this gene is defective, the enzyme derived from it may be deficient and may fail to carry out the conversion or carry it out so slowly as to result in an inefficient conversion. While the first substance, a protein, accumulates in the cell, causing a surplus, it will be in short supply in the cell involved in the conversion, resulting in a deficiency. The surplus or the shortage may eventuate in a metabolic disorder, the genetic disbalance often revealing itself in overt symptoms.
Evidence of metabolic disorders can occur at any time in a person’s life. They sometimes are detectable prenatally, but they may occur in early childhood, adolescence, adult life, or old age. In some cases, the onset of a serious metabolic disorder will be followed quickly by death. Many people suffering from such disorders, however, live long, active, full lives, many of them exceeding the average life span. Some metabolic disorders, such as diabetes, are manageable over long periods through diet and medication.
Some types of metabolic disorders can be treated successfully with massive doses of vitamins. At least twenty fairly common disorders respond favorably to such treatment. For example, Wilson disease, which results in excessive amounts of copper being accumulated in the tissues, is generally treated successfully with D-penicillamine, a compound that removes copper from the tissues and deposits it into the urinary system for excretion as urine.
Certain nutrients trigger metabolic disorders in some organisms. The avoidance of these nutrients can prevent the triggering of the disorder on a permanent basis. Also, where the disorder results from a deficiency of an end product in a reaction, the disorder may be forestalled by replacing the end product.
Perspective and Prospects
Metabolism was scarcely understood until the 1770s, 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 1890s, 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 inanimate systems.
Landmark discoveries about metabolism proceeded into the twentieth century. In 1907, Walter Fletcher and Frederick Gowland Hopkins discovered that lactic acid results when glucose is subjected to the anaerobic contraction of muscles. Five years later, Hopkins discovered substances that are now recognized as vitamins, a term invented in 1912 by Casimir Funk. Ten years later, Frederick Banting and others pinpointed insulin as a substance that could be synthesized and used to reduce levels of blood sugar in humans, thereby making diabetes a manageable rather than a clearly fatal disorder.
A turning point in the understanding of metabolism and especially of metabolic disorders came in 1926 when James B. Sumner purified the first enzyme, showing it to be a protein, clearly leading to the realization that metabolic disorders result from a faulty protein in the genes. In 1941, Fritz Lipmann established the central role of ATP as a carrier of energy in living organisms, and the following year, Rudolf Schoenheimer demonstrated that the adult body’s chemical constituents are in constant flux, suggesting that normal, healthy organisms are constantly renewing themselves.
As one surveys the future in terms of the rapidly increasing knowledge of metabolism and genetics, it is clear that
genetic engineering offers daunting biological challenges. Birth defects can be detected well before birth, and many of them, through genetic manipulation, can be prevented. It is now within the capability of genetic engineering to predetermine the sex of a fetus and to control matters of gender. Amniocentesis can reveal abnormalities by the second trimester of pregnancy, revealing such conditions as metabolic disorders.
The capabilities that currently lie within reach pose substantial ethical problems and challenges. For example, if a fetus clearly shows evidence of being afflicted with a metabolic disorder, what use should be made of this information? Some parents would elect to terminate the pregnancy, given the challenges of raising such a child.
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