Key terms:

adipose tissue: tissue that stores fat; occurs in humans beneath the skin, usually in the abdomen or the buttocks

anabolism: the metabolic activity through which complex substances are synthesized from simpler substances

basal metabolic rate (BMR): the standardized measure of metabolism in warm-blooded organisms

calorie: a measurement of heat, particularly in measuring the value of foods for producing energy and heat in an organism

catabolism: the complete breaking down of molecules by an organism to obtain chemical building blocks

essential nutrients: molecules that an organism needs for survival but cannot manufacture itself

standard metabolic rate (SMR): the standardized measure of metabolism in cold-blooded organisms

storage compounds: areas in the body that store nutrients not immediately required by an organism

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 how fast it consumes energy 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 as external work, such as walking or moving, overcomes friction. Therefore, a workable measure of metabolic rate 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. The salivary glands produce these enzymes. As a ball of food, a bolus passes through the digestive system, and additional enzymes 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 food components, 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. In contrast, 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 passing through.

Organisms typically cannot digest all the types of nutrients they ingest. Most vertebrates, for example, cannot digest cellulose, the major carbohydrate component of most plants. This material, therefore, 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 preventing colon cancer over the long term.

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 amino acids. For a cell to construct a protein, it must connect the many amino acid molecules required in a specific, complex order. While some of the requisite amino acids result directly from ingesting nutrients, others are unavailable in this way and must be obtained by synthesizing sugar molecules.

Molecules that an organism needs 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 can produce 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 rich grain. Humans, in turn, eat chickens, through which they obtain valine. This amino acid is also available to humans through their green vegetables.

Organisms ingest food to provide the necessary building blocks for synthesizing membranes, enzymes, and other parts of cells and to provide energy. Suppose the ingested nutrients exceed the body’s requirements for synthesis and energy production. In that case, 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 around the abdomen and buttocks, where they can accumulate in considerable quantities.

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 are completely depleted. Afterward, nutrients, mostly proteins, are drawn from muscle mass, the sudden reduction of which can quickly result in death.

The survival of organisms is usually dependent upon the work that they perform. Energy to carry out this work is derived through splitting the chemical bonds of adenosine triphosphate (ATP) and the splitting of the bonds of food molecules. A 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. It results in the oxidization of nutrient molecules, which are broken up into small molecules composed largely of carbon dioxide and water. In this process, energy is released; some is lost as heat, and some is conserved in the bonds of ATP.

As amino acids, lipids, and carbohydrates are catabolized in humans, the muscles use lipids and carbohydrates. In contrast, the brain gains 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 anaerobic glycolysis, which involves the creation of ATP without oxygen, energy is produced by converting glucose or glycogen into lactic acid. The body cannot excrete lactic acid, making its accumulation impossible 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 to release additional energy.

The Pathways of Metabolism

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 reduce the overall number of calories consumed. Physical activity generally helps to sustain the basal metabolism at levels higher than those found among the sedentary.

DISORDERS AND DISEASES

All metabolic disorders have genetic or environmental origins or a combination of the two. For example, a person with a genetic predisposition for diabetes, an inherited genetic disorder, may exacerbate this predisposition by indulging in a diet high in fats and carbohydrates, overindulging in alcoholic beverages, and 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 living organism cell was a major biochemical discovery. It has led to vastly increased insights into heredity and 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 abnormalities in fetuses by analyzing the amniotic fluid surrounding them in the womb. This process, known as amniocentesis, can identify over twenty inherited metabolic disorders before an infant is born. Genetic manipulation in utero can alter some metabolic disorders, bypassing or modifying faulty or abnormal genes. The genes of a person with a predisposition for a metabolic defect usually do not carry the information required for synthesizing 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 serves, a delicate balance exists within the cells. When this balance is disturbed, metabolic problems ensue. For example, a gene may produce an enzyme that converts one substance to another. If this gene is defective, the enzyme derived from it may be deficient and fail to carry out the conversion or 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 are sometimes detectable prenatally but 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 successfully treated with massive doses of vitamins. At least twenty fairly common disorders respond favorably to such treatment. For example, Wilson disease, which results in excessive copper accumulation 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. Avoiding these nutrients can permanently prevent the disorder from triggering. Also, where the disorder results from a deficiency of an end product in a reaction, replacing the end product may forestall the disorder.

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 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 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 blood sugar levels in humans, thereby making diabetes a manageable rather than a fatal disorder.

A turning point in the understanding of metabolism, 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 an energy carrier 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 can be prevented through genetic manipulation. Genetic engineering can now predetermine a fetus’s sex and 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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