Metabolism

views updated Jun 11 2018

METABOLISM

CONCEPT

The term metabolism refers to all of the chemical reactions by which complex molecules taken into an organism are broken down to produce energy and by which energy is used to build up complex molecules. All metabolic reactions fall into one of two general categories: catabolic and anabolic reactions, or the processes of breaking down and building up, respectively. The best example of metabolism from daily life occurs in the process of taking in and digesting nutrients, but sometimes these processes become altered, either through a person's choice or through outside factors, and metabolic disorders follow. Such disorders range from anorexia and bulimia to obesity. These are all examples of an unhealthy, unnatural alteration to the ordinary course of metabolism; on the other hand, hibernation allows animals to slow down their metabolic rates dramatically as a means of conserving energy during times when food is scarce.

HOW IT WORKS

The Body's Furnace

The term metabolism, strangely enough, is related closely to devil, with which it shares the Greek root ballein, meaning "to throw." By adding dia ("through" or "across"), one arrives at devil and many related words, such as diabolical ; on the other hand, the replacement of that prefix with meta ("after" or "beyond") yields the word metabolism. The connection between the two words has been obscured over time, but it might be helpful to picture metabolism in terms of an image that goes with that of a devil: a furnace.

Metabolism is indeed like a furnace, in that it burns energy, and that is the aspect most commonly associated with this concept. But metabolism also involves a function that a furnace does not: building new material. All metabolic reactions can be divided into either catabolic or anabolic reactions. Catabolism is the process by which large molecules are broken down into smaller ones with the release of energy, whereas anabolism is the process by which energy is used to build up complex molecules needed by the body to maintain itself and develop new tissue.

DIGESTION.

One way to understand the metabolic process is to follow the path of a typical nutrient as it passes through the body. The digestive process is discussed in Digestion, while nutrients are examined in Nutrients and Nutrition as well as in Proteins, Amino Acids, Enzymes, Carbohydrates, and Vitamins. Here we touch on the process only in general terms, as it relates to metabolism.

The term digestion is not defined in the essay on that subject, because it is an everyday word whose meaning is widely known. For the present purposes, however, it is important to identify it as the process of breaking down food into simpler chemical compounds as a means of making nutrients absorbable by the body. This is a catabolic process, because the molecules of which foods are made are much too large to pass through the lining of the digestive system and directly into the bloodstream. Thanks to the digestive process, smaller molecules are formed and enter the bloodstream, from whence they are carried to individual cells throughout a person's body.

The smaller molecules into which nutrients are broken down make up the metabolic pool, which consists of simpler substances. The metabolic pool includes simple sugars, made by the breakdown of complex carbohydrates; glycerol and fatty acids, which come from the conversion of lipids, or fats; and amino acids, formed by the breakdown of proteins. Substances in the metabolic pool provide material from which new tissue is constructedan anabolic process.

The chemical breakdown of substances in the cells is a complex and wondrous process. For instance, a cell converts a sugar molecule into carbon dioxide and water over the course of about two dozen separate chemical reactions. This is what cell biologists call a metabolic pathway: an orderly sequence of reactions, with particular enzymes (a type of protein that speeds up chemical reactions) acting at each step along the way. In this instance, each chemical reaction makes a relatively modest change in the sugar moleculefor example, the removal of a single oxygen atom or a single hydrogen atomand each is accompanied by the release of energy, a result of the breaking of chemical bonds between atoms.

ATPand ADP

Cells capture and store the energy released in catabolic reactions through the use of chemical compounds known as energy carriers. The most significant example of an energy carrier is adenosine triphosphate, or ATP, which is formed when a simpler compound, adenosine diphosphate (ADP), combines with a phosphate group. (A phosphate is a chemical compound that contains oxygen bonded to phosphorus, and the term group in chemistry refers to a combination of atoms from two or more elements that tend to bond with other elements or compounds in certain characteristic ways.)

ADP will combine with a phosphate group only if energy is added to it. In cells, that energy comes from the catabolism of compounds in the metabolic pool, including sugars, glycerol (related to fats), and fatty acids. The ATP molecule formed in this manner has taken up the energy previously stored in the sugar molecule, and thereafter, whenever a cell needs energy for some process, it can obtain it from an ATP molecule. The reverse of this process also takes place inside cells. That is, energy from an ATP molecule can be used to put simpler molecules together to make more complex molecules. For example, suppose that a cell needs to repair a rupture in its cell membrane. To do so, it will need to produce new protein molecules, which are made from hundreds or thousands of amino-acid molecules. These molecules can be obtained from the metabolic pool.

The reactions by which a compound is metabolized differ for various nutrients. Also, energy carriers other than ATP may play a part. For example, the compound known as nicotinamide adenine dinucleotide phosphate (NADPH) also has a role in the catabolism and anabolism of various substances. The general outline described here, however, applies to all metabolic reactions.

Catabolism and Anabolism

Energy released from organic nutrients (those containing carbon and hydrogen) during catabolism is stored within ATP, in the form of the high-energy chemical bonds between the second and third molecules of phosphate. The cell uses ATP for synthesizing cell components from simple precursors, for the mechanical work of contraction and motion, and for transport of substances across its membrane. ATP's energy is released when this bond is broken, turning ATP into ADP. The cell uses the energy derived from catabolism to fuel anabolic reactions that synthesize cell components. Although anabolism and catabolism occur simultaneously in the cell, their rates are controlled independently. Cells separate these pathways because catabolism is a "downhill" process, or one in which energy is released, while anabolism is an "uphill" process requiring the input of energy.

Catabolism and anabolism share an important common sequence of reactions known collectively as the citric acid cycle, the tricarboxylic acid cycle, or the Krebs cycle. Named after the German-born British biochemist Sir Hans Adolf Krebs (1900-1981), the Krebs cycle is a series of chemical reactions in which tissues use carbohydrates, fats, and proteins to produce energy; it is part of a larger series of enzymatic reactions known as oxidative phosphorylation. In the latter reaction, glucose is broken down to release energy, which is stored in the form of ATPa catabolic sequence. At the same time, other molecules produced by the Krebs cycle are used as precursor molecules for reactions that build proteins, fats, and carbohydratesan anabolic sequence. (A precursor is a substance, cellular component, or cell from which another substance, cellular component, or celldifferent in kind from the precursoris formed.)

Introduction to Lipids

As noted earlier, many practical aspects of metabolism are discussed elsewhere, particularly in the essays Digestion and Nutrients and Nutrition. Also, two types of chemical compound, proteins and carbohydrates, are so important to a variety of metabolic processes that they are examined in detail within entries of their own. In the present context, let us focus on the third major kind of nutrient, lipids or fats.

Lipids are soluble in nonpolar solvents, which is the reason why a gravy stain or other grease stain is difficult to remove from clothing without a powerful detergent or spot remover. Water molecules are polar, because the opposing electric charges tend to occupy opposite sides or ends of the molecule. In a molecule of oil, whether derived from petroleum or from animal or vegetable fat, electric charges are very small, and are distributed evenly throughout the molecule.

Whereas water molecules tend to bond relatively well, like a bunch of bar magnets attaching to one another at their opposing poles, oil and fat molecules tend not to bond. (The "bond" referred to here is the fairly weak one between molecules. Much stronger is the chemical bond within moleculesa bond that, when broken, brings about a release of energy, as noted earlier.) Their functions are as varied as their structures, but because they are all fat-soluble, lipids share in the ability to approach and even to enter cells. The latter have membranes that, while highly complex in structure, can be identified in simple terms as containing lipids or lipoproteins (lipids attached to proteins). The behavior of lipids and lipid-like molecules, therefore, becomes very important in understanding how a substance may or may not enter a cell. Such a substance may be toxic, as in the case of some pesticides, but if they are lipid-like, they are able to penetrate the cell's membrane. (See Food Webs for more about the biomagnification of DDT.)

In addition to lipoproteins, there are glycolipids, or lipids attached to sugars, as well as lipids attached to alcohols and some to phosphoric acids. The attachment with other compounds greatly alters the behavior of a lipid, often making them bipolarthat is, one end of the molecule is water-soluble. This is important, because it allows lipids to move out of the intestines and into the bloodstream. In the digestive process, lipids are made water-soluble either by being broken down into smaller parts or through association with another substance. The breaking down usually is done via two different processes: hydrolysis, or chemical reaction with water, and saponification. The latter, a reaction in which certain kinds of organic compounds are hydrolyzed to produce an alcohol and a salt, is used in making soap.

REAL-LIFE APPLICATIONS

Putting Lipids to Use

Derived from living systems of plants, animals, or humans, lipids are essential to good health, not only for humans but also for other animals and even plants. Seeds, for example, contain lipids for the storage of energy. Because fat is a poor conductor of heat, lipids also can function as effective insulators, and for this reason, people living in Arctic zones seek fatty foods such as blubber. Some lipids function as chemical messengers in the body, while others serve as storage areas for chemical energy. There is a good reason why babies are born with "baby fat" and why children entering puberty often tend to become chubby: in both cases, they are building up energy reserves for the great metabolic hurdles that lie ahead, and within a few years, they will have used up those excessive fat stores.

FATS AND OILS.

Fats and oils are both energy-rich compounds that are basic components of the normal diet. Both have essentially the same chemical structurea mixture of fatty acids combined with glyceroland are insoluble (do not dissolve) in water. While fats remain solid or at least semisolid at room temperature, however, most oils very quickly become liquid at increased temperatures. Animal fats and oils include butter, lard, tallow, and fish oil. Numerous other oils, such as cottonseed, peanut, and corn oils, are derived from plants.

Fats have two main functions: they provide some of the raw material for synthesizing (creating) and repairing tissues, and they serve as a concentrated source of fuel energy. Fats, in fact, provide humans with roughly twice as much energy, per unit weight, as carbohydrates and proteins. Fats are not only an important source of day-to-day energy, but they also can be stored indefinitely as adipose (fat) tissue in case of future need. Fats also help by transporting fat-soluble vitamins, such as A and D (see Vitamins), throughout the system. They cushion and form protective pads around delicate organs, such as the heart, liver and kidneys, and the layer of fat under the skin helps insulate the body against too much heat loss. They even add to the flavor of foods that might otherwise be inedible.

NOT ALL FAT IS CREATED EQUAL.

Although normal amounts of certain kinds of fat in the diet are essential to good health, unnecessarily high amounts (especially of unhealthy fats) can lead to various problems. Healthy fats include those from fatty fish, such as salmon, mackerel, or tuna, or from fat-containing vegetables, such as the avocado. In addition, many vegetable oils, particularly olive oil, can be beneficial.

Bad fats, on the other hand, are usually ones that have been tampered with through a process known as hydrogenation. This is a term describing any chemical reaction in which hydrogen atoms are added to fill in chemical bonds between carbon and other atoms, but in the case of fatty foods, hydrogenation involves the saturation of hydrocarbons, organic chemical compounds whose molecules are made up of nothing but carbon and hydrogen atoms. When they are treated with hydrogen gas, they become "saturated" with hydrogen atoms. Saturated fats, as they are called, are harder and more stable and stand up better to the heat of frying, which makes them more desirable for use in commercial products. For this reason, many foods contain hydrogenated vegetable oil; however, saturated fats have been linked to a rise in blood cholesterol levelsand to an increased risk of heart disease.

Cholesterol is a variety of lipid, and, like other lipids, some of it is essentialbut only some and only of the right kind. Most cholesterol is transported through the blood in low-density lipoproteins, or LDLs, which have been nicknamed bad cholesterol. These lipoproteins are received by LDL receptors on the cell membranes, but if there are more LDLs than LDL receptors, the excess LDLs will be deposited in the arteries. Thus, LDLs are not really "bad" unless there are too many of them. On the other hand, "good" cholesterol (HDLs, or high-density lipoproteins) help protect against damage to the artery walls by carrying excess LDLs back to the liver.

HOW MUCH IS TOO MUCH?

A certain amount of excess adipose tissue can be valuable during periods of illness, overactivity, or food shortages. Too much, however, can be unsightly and also can overwork the heart and put added stress on other parts of the body. High levels of certain circulating fats may lead to atherosclerosis, which is a thickening of the artery walls, and they have been linked to various illnesses, including cancer.

With fat, as with many things where the body is concerned, if a little is a good, this does not mean that a lot is better. In the past, nutritionists considered a diet that obtained 40% of its calories from fats a reasonable one; today, however, they recommend that no more than 30% of all calories (and preferably an even smaller percentage) come from fat. Agreement on this point, however, is far from universal. Some physicians and scientists maintain that dietary fat does not contribute as much to body fat as do carbohydrates. Carbohydrates are good for someone who needs a boost of energy that can be consumed easily by the body, such as an athlete going into competition. But for in active peopleand this includes a large portion of Americanscarbohydrates simply are stored as fat.

Experts do not even agree on the answer to a question much simpler than "How much is too much fat in the diet?"the question "How much is too much fat on the body?" Some doctors classify a person as obese whose weight is at least 20% more than the recommended weight for his or her height, but others say that standard height-and-weight charts are misleading. After all, muscle weighs more than fat, and it is conceivable that a very muscular athlete with very little body fat might qualify as "overweight" compared with the recommended weight for his or her height.

BODY FAT, THE SEXES, AND NATURE.

Because of the complexity of the issue, many experts contend that the proportion of fat to muscle, measured by the skinfold "pinch" test, is a better measure of obesity. (Being obese is not the same as being overweight: the muscular athlete described in the last paragraph is overweight but not obese, a term that implies an excess of body fat.) In healthy adults, fat typically should account for about 18-25% of the body weight in females and 15-20% in males.

The reason for the difference between men and women is that fat naturally accumulates in a woman's buttocks and thighs, because nature "assumes" that she will bear children, in which case such excess fat will be useful. This is why women over the age of about 25 often complain that when they and their husbands or boyfriends embark on a fitness program together, the men usually see results faster. The reason is that there is no genetic or evolutionary benefit to be gained from a man having fat around his waist, which is where men usually gain. If anythingsince our genetic codes and makeup have changed little since prehistorythe well-being and propagation of the human species are best served by a lean, muscular male capable of killing animals to feed and protect his family. All of this means, of course, that men should not gloat if they see better results from a regular workout program; instead, they should just recognize that nature is at work in their wives' or girlfriends' bodies as in their own.

Metabolic Disorders

Enzymes, as we noted earlier, are critical participants in metabolic reactions. They are like relay runners in a race, in this case a race along the metabolic pathways whereby nutrients are turned into energy or new bodily material. Therefore, if an enzyme is missing or does not function as it should, it can create a serious metabolic disorder. An example is phenylketonuria (PKU), caused by the lack of an enzyme known as phenylalanine hydroxylase. This enzyme is responsible for converting the amino acid phenylalanine to a second amino acid, tyrosine; when this does not happen, phenylalanine builds up in the body. It is converted to a compound called phenylpyruvate, which impairs normal brain development, resulting in severe mental retardation.

Other examples of metabolic disorders include alkaptonuria, thalassemia, porphyria, Tay-Sachs disease, Hurler syndrome, Gaucher disease, galactosemia, Cushing syndrome, diabetes mellitus, hyperthyroidism, and hypothyroidism. Most of these conditions affect a small population; however, diabetes mellitus (discussed in Noninfectious Diseases) is one of the leading killers in America. At present, no cures for metabolic disorders exist. The best approach is to diagnose such conditions as early as possible and then arrange a person's diet to deal as effectively as possible with that disorder.

Eating Disorders

Eating disorders are a different matter, because they are psychological rather than physiological conditions. No one is sure what causes eating disorders, but researchers think that family dynamics, biochemical abnormalities, and modern American society's preoccupation with thinness all may contribute. Eating disorders are virtually unknown in parts of the world where food is scarce, but in wealthy lands, such as the United States, problems of overeating, self-induced starvation, or forced purging have gained considerable attention.

Anorexia nervosa, bulimia, and obesity are the most well known types of eating disorder. The word anorexia comes from the Greek for "lack of appetite," but the problem for people with anorexia is not that they are not hungry. On the contrary, they are starving, but unlike poor people in the Third World, they are not starving as the result of a shortage of food but because they are denying themselves nutrition. They do this because they fear gaining weight, even when they are so severely underweight that they look like skeletons.

The name of a related condition, bulimia, literally means "hungry as an ox." People with this problem go on eating binges, often gorging on junk food. Then they force their bodies to get rid of the food, either by vomiting or by taking large amounts of laxatives. A third type of eating disorder, obesity, also is characterized by uncontrollable overeating, but in this case the person does not force the body to eject the food that has been consumed. That, at least, makes obesity more healthy than bulimia, but there is nothing healthy about accumulating vast amounts of body fat, as severely obese people do.

ANOREXIA AND BULIMIA.

Young people are more likely than older people to suffer anorexia or bulimia, conditions that typically become apparent at about the age of 20 years. Although both men and women can experience the problem, in fact, only about 5% of people with these eating disorders are male. And though anorexia and bulimia are closely relatedparticularly inasmuch as they are psychological in origin but can exact a heavy biological tollthere are several important differences.

People who have anorexia or bulemia often come from families with overprotective parents who have unrealistically high expectations of their children. Frequently, high expectations go hand in hand with a wealthy background, and certainly anorexia and bulimia are not conditions that typically affect the poor. Anorexia and bulimia often seem to develop after some stressful experience, such as moving to a new town, changing schools, or going through puberty. Low self-esteem, fear of losing control, and fear of growing up are common characteristics of people with these conditions. Their need for approval manifests in a quest to meet or exceed our culture's idealized concept of extreme thinness. This quest is a part of our popular culture, promoted by waiflike models whose sunken eyes stare out of fashion magazines.

Like anorexia, bulimia results in starvation, but there are behavioral, physical, and psychological differences between the two. Bulimia is both less and more dangerous: on the one hand, people who have it tend to be of normal weight or are overweight, and unlike those with anorexia, they are aware of the fact that they have a problem. On the other hand, because the effects of their behavior are not so readily apparent, it is easier for a person with bulimia to persist in the pattern of bingeing and purging for much longer.

Approximately one in five persons with bulimia has a problem with drug or alcohol use, and they pursue their binges in a way not unlike that of a guilty addict or alcoholic hiding the spent needles or empty bottles from family members. They may go from restaurant to restaurant to avoid being seen eating too much in any one place, or they may pretend to be shopping for a large dinner party when, in fact, they intend to eat all the food themselves. Because of the expense of consuming so much food, some resort to shoplifting.

During a binge, people suffering from bulimia favor high-carbohydrate foods, such as doughnuts, candy, ice cream, soft drinks, cookies, cereal, cake, popcorn, and bread, and they consume many times the number of calories they would normally consume in one day. No matter what their normal eating habits, they tend to eat quickly and messily during a binge, stuffing the food into their mouths and gulping it down, sometimes without even tasting it. Some say they get a feeling of euphoria during binges, similar to the "runner's high" that some people get from exercise. Then, when they have gorged themselves, they force the food back out, either by causing themselves to vomit or by taking large quantities of laxatives.

Regular self-induced vomiting can cause all sorts of physical problems, such as damage to the stomach and esophagus, chronic heartburn, burst blood vessels in the eyes, throat irritation, and erosion of tooth enamel from the acid in vomit. Excessive use of laxatives can induce muscle cramps, stomach pains, digestive problems, dehydration, and even poisoning, while bulimia, in general, brings about vitamin deficiencies and imbalances of critical body fluids, which, in turn, can lead to seizures and kidney failure.

The self-imposed starvation of people with anorexia likewise takes a heavy toll on the body. The skin becomes dry and flaky, muscles begin to waste away, bones stop growing and may become brittle, and the heart weakens. Seeking to protect itself in the absence of proper insulation from fat, the body sprouts downy hair on the face, back, and arms in response to lower body temperature. In women, menstruation stops, and permanent infertility may result. Muscle cramps, dizziness, fatigue, and even brain damage as well as kidney and heart failure are possible. An estimated 10% to 20% of people with anorexia die either as a direct result of starvation or by suicide.

To save people with anorexia, force-feeding may be necessary. Some 70% of anorexia patients who are treated for about six months return to normal body weight, but about 15-20% can be expected to relapse. Bulimia is not as likely as anorexia to reach life-threatening stages, so hospitalization typically is not necessary. Treatment generally calls for psychotherapy and sometimes the administration of antidepressant drugs. Unlike people with anorexia, those with bulimia usually admit they have a problem and want help overcoming it.

OBESITY.

Unlike anorexia or bulimia, obesity is more of a problem among people from lower-income backgrounds. This probably relates to a lack of education concerning nutrition, combined with the fact that healthier food is more expensive; by contrast, unhealthy items, such as white sugar, corn meal, and fatty cuts of pork and other meats can fill or overfill a person's stomach inexpensively. In addition, though men and women both tend to gain weight as they age, women are almost twice as likely as men to be obese.

Some cases of obesity relate to metabolic problems, while others stem from compulsive eating, which is psychologically motivated. Some studies suggest that obese people are much more likely than others to eat in response to stress, loneliness, or depression. And just as emotional pain can lead to obesity, obesity can lead to psychological scars. From childhood on, obese people are taunted and shunned, and throughout life they may face discrimination in school and on the job.

Physically, obesity is a killer, especially for those who are morbidly obesethat is, people whose obesity endangers their health. Obesity is a risk factor for diabetes, high blood pressure, arteriosclerosis, angina pectoralis (chest pains due to inadequate blood flow to the heart), varicose veins, cirrhosis of the liver, and kidney disease. Obese people are about 1.5 times more likely to have heart attacks than are other people, and the overall death rate among people ages 20-64 is 50% higher for the obese than for people of ordinary weight.

Hibernation

Having looked at several unnatural ways in which people alter their metabolisms, let us close with an example of a very natural way that animals sometimes temporarily change theirs. This is hibernation, a state of inactivity in which an animal's heart rate, body temperature, and breathing rate are decreased as a way to conserve energy through the cold months of winter. A similar state, known as estivation, is adopted by some desert animals during the dry months of summer.

Hibernation is a technique that animals have developed, as a result of natural selection over the generations (see Evolution), to adapt to harsh environmental conditions. When food is scarce, a nonhibernating animal would be like a business operating at a lossthat is, using more energy maintaining its body temperature and searching for food than it would receive from consuming the food. Hibernating animals use 70-100 times less energy than when they are active, allowing them to survive until food is once again plentiful.

CONTRAST WITH SLEEP.

Many animals sleep more often when food is scarce, but only a few truly hibernate. Bears, which many people think of as the classic hibernating animal, are actually just deep sleepers. By contrast, true hibernation occurs only in small mammals, such as bats and woodchucks and a few birds, among them nighthawks. Some insects also practice a form of hibernation. Hibernation differs from sleep, in that a hibernating animal shows a drastic reduction in metabolism and then awakes relatively slowly, whereas a sleeping animal decreases its metabolism only slightly and can wake up almost instantly if disturbed. Also, hibernating animals do not show periods of rapid eye movement (REM), the stage of sleep associated with dreaming in humans.

THE PROCESS OF HIBERNATION.

Animals prepare for hibernation in the fall by storing food; usually this storage is internal, in the form of fat reserves. A woodchuck in early summer may have only about 5% body fat, but as fall approaches, changes in the animal's brain chemistry cause it to feel hungry and to eat constantly. As a result, the woodchuck's body fat increases to about 15% of its total weight. In other animals, such as the dormouse, fat may constitute as much as 50% of the animal's weight by the time hibernation begins. A short period of fasting follows the feeding frenzy, to ensure that the digestive tract is emptied completely before hibernation begins.

Going into hibernation is a gradual process. Over a period of days, an animal's heart rate and breathing rate drop slowly, eventually reaching rates of just a few beats or breaths per minute. Their body temperatures also drop from levels of about 100°F (38°C) to about 60°F (15°C). The lowered body temperature makes fewer demands on metabolism and food stores. Electric activity in the brain ceases almost completely during hibernation, although some areasthose that respond to external stimuli, such as light, temperature, and noiseremain active. Thus, the hibernating animal can be aroused under extreme conditions.

Periodicallyperhaps every two weeks or sothe hibernating animal awakes and takes a few deep breaths to refresh its air supply. If the weather is particularly mild, some animals may venture from their lairs. An increase in heart rate signals that the time for arousal, or ending hibernation, is near. Blood vessels dilate, particularly around the heart, lungs, and brain, and this leads to an increased breathing rate. Eventually, the increase in circulation and metabolic activity spreads throughout the body, and the animal resumes a normal waking state.

WHERE TO LEARN MORE

Bouchard, Claude. Physical Activity and Obesity. Champaign, IL: Human Kinetics, 2000.

"KEGG Metabolic Pathways ." KEGG: Kyoto Encyclopedia of Genes and GenomesGenomeNet, Bioinformatics Center, Institute for Chemical Research, Kyoto University (Web site). <http://www.genome.ad.jp/kegg/metabolism.html>.

Medline Plus: Food, Nutrition, and Metabolism Topics. Medline, National Library of Medicine, National Insti tutes of Health (Web site). <http://www.nlm.nih.gov/medlineplus/foodnutritionandmetabolism.html>.

Metabolic Pathways of Biochemistry. George Washington University (Web site). <http://www.gwu.edu/~mpb/>.

Metabolism (Web site). <http://www.ultranet.com/~jkimball/BiologyPages/M/Metabolism.html>.

Michal, Gerhard. Biochemical Pathways: An Atlas of Bio chemistry and Molecular Biology. New York: Wiley, 1999.

Pasternak, Charles A. The Molecules Within Us: Our Body in Health and Disease. New York: Plenum, 1998.

Pathophysiology of the Digestive System (Web site). <http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/>.

Spallholz, Julian E. Nutrition, Chemistry, and Biology. Englewood Cliffs, NJ: Prentice-Hall, 1989.

Wolinsky, Ira. Nutrition in Exercise and Sport. 3d ed. Boca Raton, FL: CRC Press, 1998.

KEY TERMS

ADIPOSE:

Of or relating to animal fat.

AMINO ACIDS:

Organic compounds made of carbon, hydrogen, oxygen, nitrogen, and (in some cases) sulfur bonded in characteristic formations. Strings of amino acids make up proteins.

ANABOLISM:

The metabolic process by which energy is used to build up complex molecules that the body needs to maintain itself and develop new material.

ATOM:

The smallest particle of an element, consisting of protons, neutrons, and electrons. An atom can exist either alone or in combination with other atoms in a molecule.

ATP:

Adenosine triphosphate, an energy carrier formed when a simpler compound, adenosine diphosphate (ADP), combines with a phosphate group.

BLOOD SUGAR:

The glucose in the blood.

CARBOHYDRATES:

Naturally occur ring compounds, consisting of carbon, hydrogen, and oxygen, whose primary function in the body is to supply energy. Included in the carbohydrate group are sugars, starches, cellulose, and various other substances. Most carbohydrates are produced by green plants in the process of undergoing photosynthesis.

CATABOLISM:

The metabolic process by which large molecules are broken down into smaller ones with the release of energy. Compare with anabolism.

COMPOUND:

A substance in which atoms of more than one element are bond ed chemically to one another.

DIGESTION:

The process of breaking food down into simpler chemical compounds as a means of making the nutrients absorbable by the body or organism.

ENZYME:

A protein material that speeds up chemical reactions in the bodies of plants and animals without itself taking part in, or being consumed by, these reactions.

GLUCOSE:

A monosaccharide (sugar) that occurs widely in nature and which is the form in which animals usually receive carbohydrates. Also known as dextrose, grape sugar, and corn sugar. See also blood sugar.

HYDROCARBON:

Any organic chemical compound whose molecules are madeup of nothing but carbon and hydrogenatoms.

LIPIDS:

Fats and oils, which dissolve in oily or fatty substances but not in water-based liquids. In the body, lipids supply energy in slow-release doses, protect organs from shock and damage, and provide insulation for the body, for instance from toxins.

METABOLIC PATHWAY:

An orderly sequence of reactions, with particular enzymes acting at each step along the way. Metabolic pathways may be either linear or circular, and sometimes they are linked, meaning that the product of one pathway becomes a reactant in another.

METABOLIC POOL:

A group of relatively simple substances (e.g., amino acids) formed by the breakdown of relatively complex nutrients.

METABOLISM:

The chemical process by which nutrients are broken down and converted into energy or are used in the construction of new tissue or other material in the body. All metabolic reactions are either catabolic or anabolic.

MOLECULE:

A group of atoms, usually but not always representing more than one element, joined in a structure. Compounds typically are made up of molecules.

NUTRIENT:

Materials essential to the survival of organisms. They include proteins, carbohydrates, lipids (fats), vitamins, and minerals.

NUTRITION:

The series of processes by which an organism takes in nutrients and makes use of them for its survival, growth, and development. The term nutrition also can refer to the study of nutrients, their consumption, and their use in the organism's body.

ORGANIC:

At one time chemists used the term organic only in reference to living things. Now the word is applied to compounds containing carbon and hydrogen.

PHOSPHATE GROUP:

A group (that is, a combination of atoms from two or more elements that tend to bond with other elements or compounds in certain characteristic ways) that includes a phosphate, or a chemical compound that contains oxygen bonded to phosphorus.

PRODUCT:

A substance or substances formed from the interaction of reactants in a chemical reaction.

PROTEINS:

Large molecules built from long chains of 50 or more amino acids. Proteins serve the functions of promoting normal growth, repairing damaged tissue, contributing to the body's immune system, and making enzymes.

REACTANT:

A substance that interacts with another substance in a chemical reaction, resulting in the formation of a chemical or chemicals known as the product(s).

SUGARS:

One of the three principal types of carbohydrate, along with starches and cellulose. Sugars can be defined as any of various water-soluble carbohydrates of varying sweetness. What we think of as "sugar" (i.e., table sugar) is actually sucrose; "blood sugar," on the other hand, is glucose.

TISSUE:

A group of cells, along with the substances that join them, that forms part of the structural materials in plants oranimals.

Metabolism

views updated May 17 2018

Metabolism

Definition

Metabolism refers to the highly integrated network of chemical reactions by which living cells grow and sustain themselves.

Description

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.

Function

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 form—entropy. 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 energy-rich 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—a process called enzyme induction—assures 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.

Metabolic pathways

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 sixcarbon 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 singlecelled 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.

KEY TERMS

Coenzyme— A coenzyme is required for the enzyme to function.

Enzymes— Enzymes are protein catalysts that increase the speed of chemical reactions in the cell without themselves being changed.

Glycolysis— The major central pathway of glucose catabolism in virtually all organisms. The main function of glycolysis is to produce ATP.

Hormones— Hormones are messengers that travel to tissues or organs, where they may stimulate or inhibit specific metabolic pathways.

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.

Phenylketonuria (PKU)— A rare hereditary condition in which phenylalanine (an amino acid) is not properly metabolized. PKU may cause severe mental retardation.

Reduction— 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.

Resources

BOOKS

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.

PERIODICALS

Academic Press. Molecular Genetics and Metabolism. San Diego, CA: Harcourt Science and Technology Company. 〈http://www.apnet.com/www/journal/gm.htm〉.

The Endocrine Society. The Journal of Clinical Endocrinology & Metabolism〈http://jcem.endojournals.org/〉.

ORGANIZATIONS

Center for Inherited Disorders of Energy Metabolism, Case Western Reserve University School of Medicine, Cleveland, OH. 〈http://www.cwru.edu/2352896/med/CIDEM/cidem.htm〉.

Metabolism Foundation, 622 Leatherwood Circle, Edmond, OK 73003. 〈http://www.metabolism.net〉.

Society for Inherited Metabolic Disorders, incorporated through the State of Oregon, non-profit society. 〈http://www.simd.org〉.

Society for the Study of Inborn Errors of Metabolism, Cardiff, Wales. 〈http://www.ssiem.org/uk/ ssiemj.html〉.

Metabolism

views updated Jun 11 2018

Metabolism

Resources

Metabolism refers to the highly integrated network of chemical reactions by which living cells grow and sustain themselves. This network is 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, these two general metabolic networks have three major functions: (1) to extract energy from nutrients or solar energy; (2) to synthesize the building blocks that make up the large molecules of life: proteins, fats, carbohydrates, nucleic acids, and combinations of these substances; and (3) 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 of a in a sequence of catalytic steps known as metabolic pathways. These sequences may be composed of up to 20 enzymes, each one creating a product that becomes the substrateor raw materialfor 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.

Most such metabolic pathways are linear, that is, they begin with a specific substrate and end with a specific product. However, 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.

Among the many hundreds of chemical reactions there are only a few that are central to the activity of the cell, and these pathways are identical in most forms of life.

All reactions of metabolism, however, are part of the overall goal of the organism to maintain its internal orderliness, whether that organism is a single celled protozoan or a human. Organisms maintain this orderliness 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 organisms environment.

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. However, 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 formentropy. The dissipation of energy during metabolism represents an increase in the randomness, or disorder, of the organisms 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 reactionswhile opposite in natureare 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 energy-rich hydrogen atoms in the coenzyme nicotinamide adenine dinucleotide phosphate 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. However, 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, that is, in excess of the cells needs, the end product acts as an inhibitor of the first enzyme of the sequence. This 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 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.

Moreover, 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. Furthermore, some enzymes have two or more modulators that may be opposite in effect and have 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 mono-phosphate) 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 coordinate with each other.

Hormone 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, where it 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 offa process called enzyme inductionassures 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 aerobicrespiration, 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 pathways 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. This action 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. However, to produce glucose-6-phosphate, the liver uses 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 ten 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 3-carbon molecules derived from the original 6-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 does so. These 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 does 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 molecules 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.

The metabolic pathways discussed to this point oxidize organic matter to produce ATP. These organic compounds are made by plants and some microorganisms by photosynthesis, which takes place in organelles called chloroplasts. Using this process, these organisms synthesize organic compounds by converting the energy of sunlight into chemical energy, which is then used to convert CO2 from the atmosphere to more reduced carbon compounds, particularly sugars.

Resources

BOOKS

Elliott, William H. Biochemistry and Molecular Biology. Oxford, UK, and New York: Oxford University Press, 2005.

Germann, William J. Principles of Human Physiology. San Francisco, CA: Pearson Benjamin Cummings, 2005.

Van De Graaff, Kent M., and R. Ward Rhees, eds. Human Anatomy and Physiology: Based on Schaums Outline of Theory and Problems of Human Anatomy and Physiology. New York: McGraw-Hill, 2001.

Marc Kusinitz

Metabolism

views updated May 23 2018

Metabolism

Metabolism refers to the highly integrated network of chemical reactions by which living cells grow and sustain themselves. This network is 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, these two general metabolic networks have three major functions: (1) to extract energy from nutrients or solar energy; (2) to synthesize the building blocks that make up the large molecules of life: proteins , fats, carbohydrates, nucleic acids, and combinations of these substances; and (3) 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 of a in a sequence of catalytic steps known as metabolic pathways. 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.

Most such metabolic pathways are linear, that is, they begin with a specific substrate and end with a specific product. However, 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.

Among the many hundreds of chemical reactions there are only a few that are central to the activity of the cell, and these pathways are identical in most forms of life.

All reactions of metabolism, however, are part of the overall goal of the organism to maintain its internal orderliness, whether that organism is a single celled protozoan or a human. Organisms maintain this orderliness 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.

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 form—entropy. 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 energy-rich hydrogen atoms in the coenzyme nicotinamide adenine dinucleotide phosphate 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, that is, in excess of the cell's needs, the end product acts as an inhibitor of the first enzyme of the sequence. This 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 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.

Moreover, 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. Furthermore, some enzymes have two or more modulators that may be opposite in effect and have 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 coordinate with each other.

Hormone 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, where it 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—a process called enzyme induction—assures 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. However, to produce glucose-6-phosphate, the liver uses 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 ten 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 3-carbon molecules derived from the original 6-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 does so. These 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 does 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 7 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 molecules, 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.

The metabolic pathways discussed to this point oxidize organic matter to produce ATP. These organic compounds are made by plants and some microorganisms by photosynthesis , which takes place in organelles called chloroplasts. Using this process, these organisms synthesize organic compounds by converting the energy of sunlight into chemical energy, which is then used to convert CO2 from the atmosphere to more reduced carbon compounds, particularly sugars.

Resources

books

Alberts, Bruce, et al. Molecular Biology of The Cell. 2nd ed. New York: Garland Publishing, 1989.

Marieb, Elaine Nicpon. Human Anatomy & Physiology. 5th ed. San Francisco: Benjamin/Cummings, 2000.


Marc Kusinitz

Metabolism

views updated May 23 2018

Metabolism

Carbohydrate Metabolism

Protein Metabolism

Fat (Lipid) Metabolism

Cholesterol Metabolism

Resources

Metabolism refers to the physical and chemical processes that occur inside the cells of the body and that maintain life. Metabolism consists of anabolism (the constructive phase) and catabolism (the destructive phase, in which complex materials are broken down). The transformation of the macronutrients, carbohydrates , fats, and proteins in food to energy, and other physiological processes are parts of the metabolic process. ATP (adinosene triphosphate) is the major form of energy used for cellular metabolism.

Carbohydrate Metabolism

Carbohydrates made up of carbon, hydrogen, and oxygen atoms are classified as mono-, di-, and poly-saccharides, depending on the number of sugar units they contain. The monosaccharides—glucose, galactose, and fructose—obtained from the digestion of food are transported from the intestinal mucosa via the portal vein to the liver. They may be utilized directly for energy by all tissues; temporarily stored as glycogen in the liver or in muscle; or converted to fat, amino acids, and other biological compounds.

Carbohydrate metabolism plays an important role in both types of diabetes mellitus . The entry of glucose into most tissues—including heart, muscle, and adipose tissue—is dependent upon the presence of the hormone insulin. Insulin controls the uptake and metabolism of glucose in these cells and plays a major role in regulating the blood glucose concentration. The reactions of carbohydrate metabolism cannot take place without the presence of the B vitamins , which function as coenzymes. Phosphorous, magnesium, iron , copper, manganese, zinc , and chromium are also necessary as cofactors.

Carbohydrate metabolism begins with glycolysis , which releases energy from glucose or glycogen to form two molecules of pyruvate, which enter the Krebs cycle (or citric acid cycle), an oxygen-requiring process, through which they are completely oxidized. Before the Krebs cycle can begin, pyruvate loses a carbon dioxide group to form acetyl coenzyme A (acetyl-CoA). This reaction is irreversible and has important metabolic consequences. The conversion of pyruvate to acetyl-CoA requires the B vitamins.

The hydrogen in carbohydrate is carried to the electron transport chain, where the energy is conserved in ATP molecules. Metabolism of one molecule of glucose yields thirty-one molecules of ATP. The energy released from ATP through hydrolysis (a chemical reaction with water ) can then be used for biological work.

KEY TERMS

Adipose tissue —Tissue containing fat deposits.

Anaerobic —Without air, or oxygen.

Deamination —Removal of an NH2 group from a molecule.

Galactosemia —Inherited disorder preventing digestion of milk sugar, galactose.

Glucose —A simple sugar; the most commonly used fuel in cells.

Glycogen —Storage form of sugar.

Glycolysis —Cellular reaction that begins the breakdown of sugars.

Ketones —Chemicals produced by fat breakdown; molecule containing a double-bonded oxygen linked to two carbons.

Ketosis —Build-up of ketone bodies in the blood, due to fat breakdown.

Krebs cycle —Cellular reaction that breaks down numerous nutrients and provides building blocks for other molecules.

Lipoprotein —Blood protein that carries fats.

Mitochondria —Small bodies within a cell that harvest energy for use by the cell.

Oxidative —Related to chemical reaction with oxygen or oxygen-containing compounds.

phenylketonuria —Inherited disease marked by the inability to process the amino acid phenylalanine, causing mental retardation.

Phospholipid —A type of fat used to build cell membranes.

Sterol —Building blocks of steroid hormones; a type of lipid.

Triglyceride —A type of fat.

Only a few cells, such as liver and kidney cells, can produce their own glucose from amino acids, and only liver and muscle cells store glucose in the form of glycogen. Other body cells must obtain glucose from the bloodstream.

Under anerobic conditions, lactate is formed from pyruvate. This reaction is important in the muscle when energy demands exceed oxygen supply. Glycolysis occurs in the cytosol (fluid portion) of a cell and has a dual role. It degrades monosaccharides to generate energy, and it provides glycerol for triglyceride synthesis. The Krebs cycle and the electron transport chain occur in the mitochondria. Most of the energy derived from carbohydrate, protein , and fat is produced via the Krebs cycle and the electron transport system.

Glycogenesis is the conversion of excess glucose to glycogen. Glycogenolysis is the conversion of glycogen to glucose (which could occur several hours after a meal or overnight) in the liver or, in the absence of glucose-6-phosphate in the muscle, to lactate. Gluco-neogenesis is the formation of glucose from noncarbo-hydrate sources, such as certain amino acids and the glycerol fraction of fats when carbohydrate intake is limited. Liver is the main site for gluconeogenesis, except during starvation, when the kidney becomes important in the process. Disorders of carbohydrate metabolism include diabetes mellitus, lactose intolerance, and galactosemia.

Protein Metabolism

Proteins contain carbon, hydrogen, oxygen, nitrogen, and sometimes other atoms. They form the cellular structural elements, are biochemical catalysts, and are important regulators of gene expression. Nitrogen is essential to the formation of twenty different amino acids, the building blocks of all body cells. Amino acids are characterized by the presence of a terminal carboxyl group and an amino group in the alpha position, and they are connected by peptide bonds.

Digestion breaks protein down to amino acids. If amino acids are in excess of the body’s biological requirements, they are metabolized to glycogen or fat and subsequently used for energy metabolism. If amino acids are to be used for energy their carbon skeletons are converted to acetyl CoA, which enters the Krebs cycle for oxidation, producing ATP. The final products of protein catabolism include carbon dioxide, water, ATP, urea, and ammonia.

Vitamin B6 is involved in the metabolism (especially catabolism) of amino acids, as a cofactor in transamination reactions that transfer the nitrogen from one keto acid (an acid containing a keto group ‘-CO-’ in addition to the acid group) to another. This is the last step in the synthesis of nonessential amino acids and the first step in amino acid catabolism. Transamination converts amino acids to L-glutamate, which undergoes oxidative deamination to form ammonia, used for the synthesis of urea. Urea is transferred through the blood to the kidneys and excreted in the urine.

The glucose-alanine cycle is the main pathway by which amino groups from muscle amino acids are transported to the liver for conversion to glucose. The liver is the main site of catabolism for all essential amino acids, except the branched-chain amino acids, which are catabolized mainly by muscle and the kidneys. Plasma amino-acid levels are affected by dietary carbohydrate through the action of insulin, which lowers plasma amino-acid levels (particularly the branched-chain amino acids) by promoting their entry into the muscle.

Body proteins are broken down when dietary supply of energy is inadequate during illness or prolonged starvation. The proteins in the liver are utilized in preference to those of other tissues such as the brain. The gluconeogenesis pathway is present only in liver cells and in certain kidney cells.

Disorders of amino acid metabolism include phe-nylketonuria, albinism, alkaptonuria, type 1 tyrosi-naemia, nonketotic hyperglycinaemia, histidinaemia, homocystinuria, and maple syrup urine disease.

Fat (Lipid) Metabolism

Fats contain mostly carbon and hydrogen, some oxygen, and sometimes other atoms. The three main forms of fat found in food are glycerides (principally triacylglycerol ‘triglyceride’, the form in which fat is stored for fuel), the phospholipids, and the sterols (principally cholesterol). Fats provide 9 kilocalories per gram (kcal/g), compared with 4 kcal/g for carbohydrate and protein. Triacylglycerol, whether in the form of chylomicrons (microscopic lipid particles) or other lipoproteins, is not taken up directly by any tissue, but must be hydrolyzed outside the cell to fatty acids and glycerol, which can then enter the cell.

Fatty acids come from the diet, adipocytes (fat cells), carbohydrate, and some amino acids. After digestion, most of the fats are carried in the blood as chylomicrons. The main pathways of lipid metabolism are lipolysis, betaoxidation, ketosis, and lipogenesis.

Lipolysis (fat breakdown) and beta-oxidation occurs in the mitochondria. It is a cyclical process in which two carbons are removed from the fatty acid per cycle in the form of acetyl CoA, which proceeds through the Krebs cycle to produce ATP, CO2, and water.

Ketosis occurs when the rate of formation of ketones by the liver is greater than the ability of tissues to oxidize them. It occurs during prolonged starvation and when large amounts of fat are eaten in the absence of carbohydrate.

Lipogenesis occurs in the cytosol. The main sites of triglyceride synthesis are the liver, adipose tissue, and intestinal mucosa. The fatty acids are derived from the hydrolysis of fats, as well as from the synthesis of acetyl CoA through the oxidation of fats, glucose, and some amino acids. Lipogenesis from acetyl CoA also occurs in steps of two carbon atoms. NADPH produced by the pentose-phosphate shunt is required for this process. Phospholipids form the interior and exterior cell membranes and are essential for cell regulatory signals.

Cholesterol Metabolism

Cholesterol is either obtained from the diet or synthesized in a variety of tissues, including the liver, adrenal cortex, skin, intestine, testes, and aorta. High dietary cholesterol suppresses synthesis in the liver but not in other tissues.

Carbohydrate is converted to triglyceride utilizing glycerol phosphate and acetyl CoA obtained from glycolysis. Ketogenic amino acids, which are metabolized to acetyl CoA, may be used for synthesis of triglycerides . The fatty acids cannot fully prevent protein breakdown, because only the glycerol portion of the triglycerides can contribute to gluconeogenesis. Glycerol is only 5% of the triglyceride carbon.

Most of the major tissues (e.g., muscle, liver, kidney) are able to convert glucose, fatty acids, and amino acids to acetyl-CoA. However, brain and nervous tissue—in the fed state and in the early stages of starvation—depend almost exclusively on glucose. Not all tissues obtain the major part of their ATP requirements from the Krebs cycle. Red blood cells, tissues of the eye, and the kidney medulla gain most of their energy from the anaerobic conversion of glucose to lactate.

Resources

BOOKS

Bland, Jeffrey S.; Costarella, L.; Levin, B.; Liska, DeAnn; Lukaczer, D.; Schiltz, B.; and Schmidt, M. A. (1999). Clinical Nutrition: A Functional Approach. Gig Harbor, WA: Institute of Functional Medicine.

Linder, Maria (1991). Nutritional Biochemistry and Metabolism, with Clinical Applications, 2nd edition. New York: Elsevier.

Newsholme E. A., and Leech, A. R. (1994). Biochemistry for the Medical Sciences. New York: Wiley.

Salway, J. G. 1999. Metabolism at a Glance, 2nd edition. Malden, MA: Blackwell Science.

Shils, M. E.; Olson, J. A.; Shike, M.; and Ross C. A.; eds. (1999). Modern Nutrition in Health and Disease, 9th edition. Baltimore, MD: Wilkins & Wilkins.

Wardlaw, Gordon M., and Kessel Margaret (2002). Perspectives in Nutrition, 5th edition. Boston: McGraw-Hill.

Williams, M. H. (1999). Nutrition for Health, Fitness, and Sport, 6th edition. Boston: McGraw-Hill.

Yeung, D. L., ed. (1995). Heinz Handbook of Nutrition, 8th edition. Pittsburgh, PA: Heinz Corporate Research Center.

Ziegler, Ekhard E., and Filer, L. J. (1996). Present Knowledge in Nutrition, 7th edition. Washington, DC: International Life Sciences Institute Press.

Zubay, Geoffrey L.; Parson, William W.; and Vance, Dennis E. (1995). Principles of Biochemistry. Dubuque, IA: William C. Brown.

Gita Patel

Mexican diet seeCentral American and Mexican diet

Micronesian diet seePacific Islander diet

Middle Eastern diet seeGreek and Middle Eastern diet

Metabolism

views updated May 17 2018

Metabolism

Metabolism refers to the physical and chemical processes that occur inside the cells of the body and that maintain life. Metabolism consists of anabolism (the constructive phase) and catabolism (the destructive phase, in which complex materials are broken down). The transformation of the macronutrients carbohydrates , fats, and proteins in food to energy , and other physiological processes are parts of the metabolic process. ATP (adinosene triphosphate) is the major form of energy used for cellular metabolism.

Carbohydrate Metabolism

Carbohydrates made up of carbon, hydrogen, and oxygen atoms are classified as mono-, di-, and polysaccharides, depending on the number of sugar units they contain. The monosaccharidesglucose , galactose, and fructoseobtained from the digestion of food are transported from the intestinal mucosa via the portal vein to the liver. They may be utilized directly for energy by all tissues; temporarily stored as glycogen in the liver or in muscle; or converted to fat , amino acids , and other biological compounds.

Carbohydrate metabolism plays an important role in both types of diabetes mellitus. The entry of glucose into most tissuesincluding heart, muscle, and adipose tissue is dependent upon the presence of the hormone insulin . Insulin controls the uptake and metabolism of glucose in these cells and plays a major role in regulating the blood glucose concentration. The reactions of carbohydrate metabolism cannot take place without the presence of the B vitamins , which function as coenzymes. Phosphorous, magnesium, iron , copper, manganese, zinc and chromium are also necessary as cofactors.

Carbohydrate metabolism begins with glycolysis , which releases energy from glucose or glycogen to form two molecules of pyruvate, which enter the Krebs cycle (or citric acid cycle), an oxygen-requiring process, through which they are completely oxidized. Before the Krebs cycle can begin, pyruvate loses a carbon dioxide group to form acetyl coenzyme A (acetyl-CoA). This reaction is irreversible and has important metabolic consequences. The conversion of pyruvate to acetyl-CoA requires the B vitamins.

The hydrogen in carbohydrate is carried to the electron transport chain, where the energy is conserved in ATP molecules. Metabolism of one molecule of glucose yields thirty-one molecules of ATP. The energy released from ATP through hydrolysis (a chemical reaction with water) can then be used for biological work.

Only a few cells, such as liver and kidney cells, can produce their own glucose from amino acids, and only liver and muscle cells store glucose in the form of glycogen. Other body cells must obtain glucose from the bloodstream.

Under anaerobic conditions, lactate is formed from pyruvate. This reaction is important in the muscle when energy demands exceed oxygen supply. Glycolysis occurs in the cytosol (fluid portion) of a cell and has a dual role. It degrades monosaccharides to generate energy, and it provides glycerol for triglyceride synthesis. The Krebs cycle and the electron transport chain occur in the mitochondria . Most of the energy derived from carbohydrate, protein, and fat is produced via the Krebs cycle and the electron transport system.

Glycogenesis is the conversion of excess glucose to glycogen. Glycogenolysis is the conversion of glycogen to glucose (which could occur several hours after a meal or overnight) in the liver or, in the absence of glucose-6-phosphate in the muscle, to lactate. Gluconeogenesis is the formation of glucose from noncarbohydrate sources, such as certain amino acids and the glycerol fraction of fats when carbohydrate intake is limited. Liver is the main site for gluconeogenesis, except during starvation, when the kidney becomes important in the process. Disorders of carbohydrate metabolism include diabetes mellitus, lactose intolerance , and galactosemia .

Protein Metabolism

Proteins contain carbon, hydrogen, oxygen, nitrogen , and sometimes other atoms. They form the cellular structural elements, are biochemical catalysts, and are important regulators of gene expression . Nitrogen is essential to the formation of twenty different amino acids, the building blocks of all body cells. Amino acids are characterized by the presence of a terminal carboxyl group and an amino group in the alpha position, and they are connected by peptide bonds.

Digestion breaks protein down to amino acids. If amino acids are in excess of the body's biological requirements, they are metabolized to glycogen or fat and subsequently used for energy metabolism. If amino acids are to be used for energy their carbon skeletons are converted to acetyl CoA, which enters the Krebs cycle for oxidation, producing ATP. The final products of protein catabolism include carbon dioxide, water, ATP, urea, and ammonia.

Vitamin B6 is involved in the metabolism (especially catabolism) of amino acids, as a cofactor in transamination reactions that transfer the nitrogen from one keto acid (an acid containing a keto group [-CO-] in addition to the acid group) to another. This is the last step in the synthesis of nonessential amino acids and the first step in amino acid catabolism. Transamination converts amino acids to L-glutamate, which undergoes oxidative deamination to form ammonia, used for the synthesis of urea. Urea is transferred through the blood to the kidneys and excreted in the urine.

The glucose-alanine cycle is the main pathway by which amino groups from muscle amino acids are transported to the liver for conversion to glucose. The liver is the main site of catabolism for all essential amino acids, except the branched-chain amino acids, which are catabolized mainly by muscle and the kidneys. Plasma amino-acid levels are affected by dietary carbohydrate through the action of insulin, which lowers plasma amino-acid levels (particularly the branched-chain amino acids) by promoting their entry into the muscle.

Body proteins are broken down when dietary supply of energy is inadequate during illness or prolonged starvation. The proteins in the liver are utilized in preference to those of other tissues such as the brain. The gluconeogenesis pathway is present only in liver cells and in certain kidney cells.

Disorders of amino acid metabolism include phenylketonuria , albinism, alkaptonuria, type 1 tyrosinaemia, nonketotic hyperglycinaemia, histidinaemia, homocystinuria, and maple syrup urine disease.

Fat (Lipid) Metabolism

Fats contain mostly carbon and hydrogen, some oxygen, and sometimes other atoms. The three main forms of fat found in food are glycerides (principally triacylglycerol [triglyceride], the form in which fat is stored for fuel), the phospholipids , and the sterols (principally cholesterol ). Fats provide 9 kilocalories per gram (kcal/g), compared with 4 kcal/g for carbohydrate and protein. Triacylglycerol, whether in the form of chylomicrons (microscopic lipid particles) or other lipoproteins , is not taken up directly by any tissue, but must be hydrolyzed outside the cell to fatty acids and glycerol, which can then enter the cell.

Fatty acids come from the diet , adipocytes (fat cells), carbohydrate, and some amino acids. After digestion, most of the fats are carried in the blood as chylomicrons. The main pathways of lipid metabolism are lipolysis, betaoxidation, ketosis , and lipogenesis.

Lipolysis (fat breakdown) and beta-oxidation occurs in the mitochondria. It is a cyclical process in which two carbons are removed from the fatty acid per cycle in the form of acetyl CoA, which proceeds through the Krebs cycle to produce ATP, CO2, and water.

Ketosis occurs when the rate of formation of ketones by the liver is greater than the ability of tissues to oxidize them. It occurs during prolonged starvation and when large amounts of fat are eaten in the absence of carbohydrate.

Lipogenesis occurs in the cytosol. The main sites of triglyceride synthesis are the liver, adipose tissue, and intestinal mucosa. The fatty acids are derived from the hydrolysis of fats, as well as from the synthesis of acetyl CoA through the oxidation of fats, glucose, and some amino acids. Lipogenesis from acetyl CoA also occurs in steps of two carbon atoms. NADPH produced by the pentose-phosphate shunt is required for this process. Phospholipids form the interior and exterior cell membranes and are essential for cell regulatory signals.

Cholesterol Metabolism

Cholesterol is either obtained from the diet or synthesized in a variety of tissues, including the liver, adrenal cortex, skin, intestine, testes, and aorta. High dietary cholesterol suppresses synthesis in the liver but not in other tissues.

Carbohydrate is converted to triglyceride utilizing glycerol phosphate and acetyl CoA obtained from glycolysis. Ketogenic amino acids, which are metabolized to acetyl CoA, may be used for synthesis of triglycerides. The fatty acids cannot fully prevent protein breakdown, because only the glycerol portion of the triglycerides can contribute to gluconeogenesis. Glycerol is only 5 percent of the triglyceride carbon.

Most of the major tissues (e.g., muscle, liver, kidney) are able to convert glucose, fatty acids, and amino acids to acetyl-CoA. However, brain and nervous tissuein the fed state and in the early stages of starvationdepend almost exclusively on glucose. Not all tissues obtain the major part of their ATP requirements from the Krebs cycle. Red blood cells, tissues of the eye, and the kidney medulla gain most of their energy from the anaerobic conversion of glucose to lactate.

see also Carbohydrates; Fats; Nutrients; Protein.

Gita Patel

Bibliography

Bland, Jeffrey S.; Costarella, L.; Levin, B.; Liska, DeAnn; Lukaczer, D.; Schiltz, B.; and Schmidt, M. A. (1999). Clinical Nutrition: A Functional Approach. Gig Harbor, WA: Institute of Functional Medicine.

Linder, Maria (1991). Nutritional Biochemistry and Metabolism, with Clinical Applications, 2nd edition. New York: Elsevier.

Newsholme E. A., and Leech, A. R. (1994). Biochemistry for the Medical Sciences. New York: Wiley.

Salway, J. G. 1999. Metabolism at a Glance, 2nd edition. Malden, MA: Blackwell Science.

Shils, M. E.; Olson, J. A.; Shike, M.; and Ross C. A.; eds. (1999). Modern Nutrition in Health and Disease, 9th edition. Baltimore, MD: Wilkins & Wilkins.

Wardlaw, Gordon M., and Kessel Margaret (2002). Perspectives in Nutrition, 5th edition. Boston: McGraw-Hill.

Williams, M. H. (1999). Nutrition for Health, Fitness, and Sport, 6th edition. Boston: McGraw-Hill.

Yeung, D. L., ed. (1995). Heinz Handbook of Nutrition, 8th edition. Pittsburgh, PA: Heinz Corporate Research Center.

Ziegler, Ekhard E., and Filer, L. J. (1996). Present Knowledge in Nutrition, 7th edition. Washington, DC: International Life Sciences Institute Press.

Zubay, Geoffrey L.; Parson, William W.; and Vance, Dennis E. (1995). Principles of Biochemistry. Dubuque, IA: William C. Brown.

metabolism

views updated Jun 11 2018

metabolism According to the Shorter Oxford English Dictionary, the term metabolism is defined as ‘the chemical processes by which nutritive material is built up into living matter, or by which complex molecules are broken down into simpler substances during the performance of special functions’. The various reactions which involve the synthesis of complex molecules can be grouped under the heading of anabolism, whereas the breakdown of complex molecules is known as catabolism. As might be expected, both anabolic and catabolic processes include a vast number of different chemical reactions, but there are a number of common features. Most of the metabolic processes occur inside the cells of the body, mainly in the cytoplasm, but also inside intracellular organelles such as the mitochondria. Anabolic and catabolic reactions involve the action of enzymes and the utilization of energy. In some cases the metabolic processes are regulated locally, i.e. by the cell itself, but often the metabolism of the whole body is controlled in an integrated fashion by the action of hormones and/or the nervous system.

Anabolic processes

These mainly involve the use of the carbohydrates, fats, proteins, and minerals consumed in the diet to synthesize complex molecules — such as the structural material of the skeleton, connective tissue, and cell membranes; nutrient stores for later use; and hormones and proteins which are secreted from cells into the blood or into the digestive tract. In order for these anabolic processes to proceed efficiently, it is essential that the cells are provided with the correct raw materials (and are able to extract them from the blood) and that the appropriate enzymes are present within the cells. Obviously, these enzymes will have been synthesized within the cells, as a result of activation of the appropriate genes in the cell nucleus.

Catabolic processes

These can be classified into a variety of categories, including the breakdown of energy-containing components of the diet (or their storage forms) to make energy available for the cells; the removal and breakdown of potentially toxic substances in the bloodstream; and the breakdown of damaged cells and tissues with the re-use of many of the components. These catabolic processes require the presence of the appropriate enzymes; many also require oxygen to be available, and the waste products to be removed from the tissues by the blood.

In many cases the processes of anabolism and catabolism occur coincidentally. A good example relates to the protein in the body, which is in a constant state of flux. Every day some of the body protein undergoes catabolism and is replaced by new material. Thus, there is a constant turnover of protein in the body, which requires a continuous supply of protein in the diet, and which also uses a substantial amount of energy.

Control of metabolism

For the body to function efficiently, there has to be an effective means of controlling and integrating the metabolic processes occurring in all the cells, tissues, and organs. This integration and control is mainly achieved by circulating hormones, with their release being regulated in turn partly by the nervous system and partly by direct effects of substances in the blood on the endocrine glands. An example of this integrated control of metabolism is the way in which blood glucose concentration is regulated to ensure an adequate supply of glucose to the brain. After meals, the hormone insulin acts to promote storage of glucose in the form of glycogen in the liver. The brain continuously extracts glucose from the blood to use as a fuel for its metabolic processes. In the periods between meals, this continued use of blood glucose causes the concentration to fall, which could impair brain function. However, a fall in blood glucose is detected in the pancreas and leads to the release of the hormone glucagon, which acts on the liver to cause breakdown of glycogen and release of glucose into the blood. In addition, if blood glucose falls sufficiently to affect brain metabolism, the sympathetic nervous system is activated, causing the adrenal gland to release adrenaline, which also stimulates the release of glucose from the liver; also the individual feels hungry and is prompted to eat.

Energy metabolism

A fundamental feature of both anabolic and catabolic processes is the utilization of energy. Almost all of the chemical reactions in the body require the expenditure of energy, which is made available mainly by the catabolism of the ‘macronutrients’: fats and carbohydrates (particularly glucose), and (to a small extent) proteins. This utilization of energy can be compared with the use of fuel for cooking or for generating electricity. In these two cases, the combustion of a fuel (coal, gas, or oil) produces carbon dioxide and water and releases heat which is used to warm the food (often causing chemical changes in it) or to generate steam to drive turbines. In the body's metabolism, the energy released from the oxidation of the macronutrients is used for a series of chemical reactions, instead of being released only as heat.

The main way in which the energy contained in the macronutrients is used in metabolism is via the substance adenosine triphosphate (ATP). Cells require energy for their metabolic processes, so they contain the enzymes and organelles needed to produce ATP from the catabolism of fats, carbohydrates, and/or proteins. In most cases, the production of ATP occurs in association with the oxidation, so that the final products are ATP, carbon dioxide, and water, as illustrated below for the oxidation of glucose (C6H12O6):C6H12O6 + 6O2 = 6CO2 + 6H2O + ATPThis is an example of aerobic metabolism, requiring the supply of oxygen and the removal of carbon dioxide from the cells by the circulating blood. Thus, in order for this predominant type of metabolism to proceed effectively in the whole body, there needs to be integration of the respiration, circulation, and supply of nutrients.

In some situations, anaerobic metabolism can occur — ATP is produced without the use of oxygen — but the energy-releasing capacity of these systems is very small compared with that of aerobic metabolism, and the anaerobic reactions lead to the production of waste products such as lactic acid which impair cell function if they are present in high concentrations.

ATP is the single most important molecule for the metabolism of almost all the cells of the body. It is used to release the energy needed for muscles to contract, for chemical bonds to be made during the synthesis of complex molecules, and for other bonds to be broken during catabolic processes. Cells do not store large quantities of ATP, but rather produce it when it is needed. Thus, most cells of the body need to regulate the concentration of ATP within them. This occurs via the effects of ATP, and its immediate breakdown product ADP (adenosine diphosphate), on the enzymes responsible for synthesizing ATP: when more ATP is used, its concentration falls, and that of ADP rises, leading to the activation of the enzyme which synthesizes more ATP. This in turn requires more oxygen to be used, and nutrients to be broken down.

An example of the complex integration of metabolism is provided by considering the processes involved in muscle contraction during exercise. This involves the brain and other parts of the nervous system in the initiation of voluntary muscle contraction and movement. Contraction can occur only if ATP is available within the muscle cells. As the ATP already present is used, so the concentration of ADP will rise, which stimulates more ATP production. At the same time the contraction of the muscles stimulates the breakdown of the intramuscular glycogen, and may also stimulate the uptake of glucose and fatty acids from the blood. The increased availability of these fuels is accompanied by stimulation of their oxidation, so the ATP concentration is maintained, and muscle contraction continues, supported by an increase in aerobic energy metabolism. For this to be possible, it is also necessary for the supply of blood to the muscles to increase, in order to deliver more oxygen and carry away more carbon dioxide and heat; the action of chemical products of local metabolism, which dilate local blood vessels, effectively links flow to requirement.

The above examples illustrate the complexity of metabolism in the human body, and show that for normal function it is essential that local processes are co-ordinated and integrated throughout the body.

I. A. Macdonald


See also blood sugar; exercise; hunger.

Metabolism

views updated Jun 08 2018

Metabolism

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.

Words to Know

Anabolism: The process by which energy is used to build up complex molecules.

ATP (adenosine triphosphate): A molecule used by cells to store energy.

Carbohydrate: A compound consisting of carbon, hydrogen, and oxygen found in plants and used as a food by humans and other animals.

Catabolism: The process by which large molecules are broken down into smaller ones with the release of energy.

Chemical bond: A force of attraction between two atoms.

Enzyme: Chemical compounds that act as catalysts, increasing the rate at which reactions take place in a living organism.

Metabolic pool: The total amount of simple molecules formed by the breakdown of nutrients.

Nutrient: A substance that helps an organism stay alive, remain healthy, and grow.

Protein: Large molecules that are essential to the structure and functioning of all living cells.

Assume, for example, that a person has just eaten a piece of bread. An important nutrient in that bread is starch, a complex carbohydrate. As soon as the bread enters a person's mouth, digestion begins to occur. Enzymes in the mouth start to break down molecules of starch and convert them into smaller molecules of simpler substances: sugars. This process can be observed easily, since anyone who holds a piece of bread in his or her mouth for a period of time begins to recognize a sweet taste, the taste of the sugar formed from the breakdown of starch.

Digestion is a necessary first step for all foods. The molecules of which foods are made are too large to pass through the lining of the digestive system. Digestion results in the formation of smaller molecules that are able to pass through that lining and enter the person's bloodstream. Sugar molecules formed by the digestion of starch enter the bloodstream. Then they are carried to individual cells throughout a person's body.

The smaller molecules into which nutrients are broken down make up the metabolic pool. The metabolic pool consists of the simpler substances formed by the breakdown of nutrients. It includes simple sugars (formed by the breakdown of complex carbohydrates), glycerol and fatty acids (formed by the breakdown of lipids), and amino acids (formed by the breakdown of proteins). Cells use substances in the metabolic pool as building materials, just as a carpenter uses wood, nails, glue, staples, and other materials for the construction of a house. The difference is, of course, that cells construct body parts, not houses, from the materials with which they have to work.

Cellular metabolism

Substances that make up the metabolic pool are transported to individual cells by the bloodstream. They pass through cell membranes and enter the cell interior. Once inside a cell, a compound undergoes further metabolism, usually in a series of chemical reactions. For example, a sugar molecule is broken down inside a cell into carbon dioxide and water, with the release of energy. But that process does not occur in a single step. Instead, it takes about two dozen separate chemical reactions to convert the sugar molecule to its final products. Each chemical reaction involves a relatively modest change in the sugar molecule, the removal of a single oxygen atom or a single hydrogen atom, for example.

The purpose of these reactions is to release energy stored in the sugar molecule. To explain that process, one must know that a sugar molecule consists of carbon, hydrogen, and oxygen atoms held together by means of chemical bonds. A chemical bond is a force of attraction between two atoms. That force of attraction is a form of energy. A sugar molecule with two dozen chemical bonds can be thought of as containing two dozen tiny units of energy. Each time a chemical bond is broken, one unit of energy is set free.

Cells have evolved remarkable methods for capturing and storing the energy released in catabolic reactions. Those methods make use of very special chemical compounds, known as energy carriers. An example of such compounds is adenosine triphosphate, generally known as ATP. ATP is formed when a simpler compound, adenosine diphosphate (ADP), combines with a phosphate group. The following equation represents that change:

ADP + P ATP

ADP will combine with a phosphate group, as shown here, only if energy is added to it. In cells, that energy comes from the catabolism of compounds in the metabolic pool, such as sugars, glycerol, and fatty acids. In other words:

catabolism: sugar carbon dioxide + water + energy;
energy from catabolism + ADP + P ATP

The ATP molecule formed in this way, then, has taken up the energy previously stored in the sugar molecule. Whenever a cell needs energy for some process, it can obtain it from an ATP molecule.

The reverse of the process shown above also takes place inside cells. That is, energy from an ATP molecule can be used to put simpler molecules together to make more complex molecules. For example, suppose that a cell needs to repair a break in its cell wall. To do so, it will need to produce new protein molecules. Those protein molecules can be made from amino acids in the metabolic pool. A protein molecule consists of hundreds or thousands of amino acid molecules joined to each other:

Amino acid 1 + amino acid 2 + amino acid 3 + (and so on) a protein

The energy needed to form all the new chemical bonds needed to hold the amino acid units together comes from ATP molecules. In other words:

energy from ATP + many amino acids protein molecule

The reactions by which a compound is metabolized differ for various nutrients. Also, energy carriers other than ATP may be involved. For example, the compound known as nicotinamide adenine dinucleotide phosphate (NADPH) is also involved in the catabolism and anabolism of various substances. The general outline shown above, however, applies to all metabolic reactions.

Metabolism

views updated Jun 11 2018

Metabolism


Metabolism refers to all of the chemical processes that take place in an organism when it obtains and uses energy. Metabolism can be divided into two major phases in which substances are broken down and other substances are made. All organisms conduct both phases constantly.

If the body of a living thing is thought of as a machine, then its metabolism is similar to a running motor. In an organism, however, the motor is not only never turned off, but it is able to monitor itself and make adjustments according to internal and external changes that are always taking place. The job of the entire organism, just like the job of every living cell, is to conduct metabolic reactions continuously. These reactions all center around the processing and use of energy. Such reactions are needed by cells and the entire organism to constantly fuel itself, repair itself, and grow. The entire range of these chemical reactions make up an organism's metabolism.

TYPES OF METABOLISM

Metabolism can be divided into two phases or categories: catabolic metabolism (catabolism) and anabolic metabolism (anabolism). Catabolism is also known as destructive metabolism. It involves the breaking down of the molecules in nutrients taken in and the release of the energy they contain. Through catabolic processes, complex compounds like fats, carbohydrates, and proteins, are degraded (broken down) into simple molecules so their energy can be released. Catabolism takes place in the body when food is digested. However, if the system needs energy and no food is available, catabolism can also break down the body's stored fat and protein.

Anabolism is also called biosynthesis or constructive metabolism and can be considered the reverse of catabolism. By its different names, it is apparent that these types of chemical reactions involve the synthesis or the making of essential, complex molecules from simpler components. Anabolism is the body's building-up phase in which it uses the complex substances it has just formed for growth and overall body maintenance. For instance, by combining amino acids (the building blocks of protein molecules), the body's cells can form structural proteins and use them to repair and replace worn-out tissues. It can also form functional proteins such as enzymes to speed up chemical reactions, antibodies to fight disease, and hormones to regulate body processes.

The remarkable thing about an organism's metabolism is that its two phases of chemical reactions are going on constantly, stopping only when the organism dies. This constant and highly complex level of chemical activity has built-in control mechanisms that regularly monitor and adjust to all sorts of changing conditions. Hormones control metabolism, and thyroxine, which is secreted by the thyroid gland, determines the rate of metabolism (meaning the rate at which the body uses up energy to perform a certain metabolic function). The pancreas determines whether anabolism or catabolism is being performed, and then releases either insulin or glucagon. Since eating causes the level of glucose in the blood to rise, the pancreas responds by releasing insulin which, in turn, starts the process of anabolism. If the glucose level is low, the pancreas releases the hormone glucagon, which triggers the catabolic processes.

THE BASAL METABOLISM RATE (BMR)

A person's metabolic rate, or the rate at which it releases energy, is influenced by a number of factors, such as an individual's age, sex, level of activity, general health, and hormone levels. Because an individual's metabolic rate can provide a doctor with a great deal of information, it often needs to be measured. Since almost all of the energy used by the body is eventually converted to heat, the metabolic rate is usually calculated by measuring the amount of heat loss an individual displays during basal (resting) conditions. A person's Basal Metabolism Rate (BMR), therefore, measures the amount of energy the body consumes in performing its maintenance operations, like normal breathing, heart beating, and minor movements while it is at rest (but not asleep). A person's BMR is then judged to be normal or abnormal by comparing it to standardized rates or rates that reflect the average BMR of healthy individuals of various ages.

Typically, the BMR of males is higher than that of females, and both sexes have a lower BMR as they age. A recent discovery relates metabolism to the aging process, since animal studies suggest that there is some connection between substantially reducing calorie intake and living longer. It has yet to be determined what role metabolism plays in this phenomenon.

SANTORIO SANTORIO

Italian physiologist Santorio Santorio (1561–1636) founded the modern study of animal metabolism (all of the chemical processes that take place in an organism when it obtains and uses energy). He introduced the idea of quantification (number or quantity of) and measurement into the study of human physiology (the study of how different processes in living things work) and used mathematics and experimentation as his tools. He was an original thinker who was far ahead of his time.

As part of a tradition that was not unusual for Italy, Santorio was given the same first name as his last. Even when he became well-known and his name was Latinized as Sanctorius Sanctorius, it was still the same double name. He was born in Capodistria (what is now Croatia), and his father was an official in the Republic of Venice. Santorio was soon sent to Venice where he was educated by tutors. He began the study of philosophy and medicine at the age of fourteen, and obtained his medical degree from the University of Padua in 1582. For the next decade or so, it is unclear whether he spent time in Poland working as a physician for the king. Biographers disagree, but it is known that he was often in Venice during this period. In 1611, however, he was appointed professor of theoretical medicine at the University of Padua on the strength of a medical book he had written in 1602. At Padua he was a very popular lecturer, and students came from all over Europe to attend.

It was in this 1602 medical book that he first began writing about how important it was to measure things exactly when doing physiology. He also stressed that close and careful observation was equally important. Ten years later he published another medical book based on his more extensive research, and in it he described his use of a type of thermometer, probably invented by Italian physicist and astronomer Galileo Galilei (1564–1642), which he adapted to measure the warmth of the body. He was thus the first physician to use a thermometer on a person and to write about it. This could be said to be the first clinical thermometer. In yet another book written in 1614, Santorio described his experiment weighing a human being every day to determine the influence of everything that went into and came out of a body, including perspiration. He even designed an apparatus that had a chair built onto a large scale and was able to prove with this that people lost weight by the evaporation of their perspiration. His ability to measure all things related to the body was further improved when he invented a device to measure a person's pulse rate. For more than twenty-five years, Santorio performed experiments on more than 10,000 subjects, using scales and similar measuring instruments. This led modern biologists to call him "the father of the science of metabolism." If metabolism can be described as all of the chemical processes that take place in a living thing, then metabolism is indeed what Santorio was pioneering.

However, his work did not have any great impact on the science of his era, and many scientists believe it is because he was simply too far ahead of his time. Nonetheless, as science progressed, his modern ideas came to be more understood and appreciated. Santorio always stressed the importance of measurement, facts, and solid information, and regularly argued against such unscientific practices as astrology (the use of stars and planets to predict their influence on human affairs). He was in favor of applying all the new tools and instruments that science had in its possession to the study of the human body. Although he did not know the word for what he was doing, he was studying what is now called human metabolism.

Finally, since enzymes and hormones play such a key role in every metabolic process, a glandular problem or a genetic fault that affects the production of an enzyme can result in major metabolism problems. Such conditions as diabetes and Addison's disease throw a person's metabolism off severely, while other people simply cannot tolerate or process certain foods, like milk.

Metabolism

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Metabolism

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