BIOLOGICAL ENERGY USE, CELLULAR PROCESSES OF

Just as an internal combustion engine requires fuel to do work, animals need fuel to power their body processes. Animals take in complex molecules as food and break them down to release the energy they contain. This process is called "catabolism." Animals use the energy of catabolism to do work and to assemble complex molecules of their own from simple building blocks, a process called "anabolism." The sum of anabolism and catabolism is "metabolism," a broad term that includes all chemical reactions in the body.

LIVING SYSTEMS FOLLOW THE RULES OF THERMODYNAMICS

Living organisms are extremely complex. Perhaps this is the reason we often forget that all animals, including people, are made up entirely of chemicals and that these chemicals react with each other according to the same rules that govern chemical reactions in test tubes. Indeed, as recently as the 1800s some scientists believed that living organisms contained a "vital force" not found in inanimate objects that was necessary for life and controlled life processes. This idea, known as vitalism, is now rejected by science because this vital force has never been found and we can explain the chemical reactions in the body without resorting to the mystical thinking inherent in vitalism.

Two energy laws that apply to both living and non-living systems are the first and second laws of thermodynamics. The first law states that energy can be neither created nor destroyed, but can only be changed from one form to another. The second law states that the "entropy" (randomness, given the symbol S) of a closed system will increase spontaneously over time. At first glance, this second law would seem to make life itself impossible because living organisms increase in order and complexity (negative S) as they develop, and then maintain this order throughout adulthood. However, living organisms are not closed systems. They are able to maintain and even decrease their entropy through the input of energy from food (animals) or sunlight (plants).

The amount of energy contained in the bonds of a chemical is called the "free energy" of that chemical (given the symbol G). To understand how free energy and entropy are related, consider the following chemical reaction: The complex substrate molecule (AB) is broken down to simpler product molecules (A and B). The substrate and the products each have both a free energy and an entropy. For this, and for all chemical reactions the following relationship applies: where H stands for heat given off or taken up during the reaction and T stands for the absolute temperature of the reaction. G and S stand for free energy and entropy, and the Δ symbol means "change in" the variable during the reaction. Thus, Equation (2) can be stated as follows: for any chemical reaction, the change in free energy between the substrates and the products (ΔG= free energy of products - free energy of substrates) is equal to the amount of heat given off or taken up during the reaction (ΔH) minus the product of the reaction temperature times the change in entropy between the substrates and the products (ΔS = entropy of products - entropy of substrates). Reactions that give off heat are called "exothermic" reactions and have negative ΔH values. Reactions that take up heat are called "endothermic" reactions and have positive ΔH values.

According to the second law of thermodynamics, for a reaction to proceed spontaneously it must produce an increase in entropy (ΔS> 0). Because most spontaneous chemical reactions in the body are exothermic (ΔH < 0), most spontaneous chemical reactions will have ΔG values less than zero as well. This means that if, in the reaction shown in Equation (1) above, we begin with equal amounts of substrates and products ([AB] = [A] × [B]), the reaction will proceed spontaneously (AB will be converted spontaneously to A and B) because the free energy contained in the bonds of AB is greater than the free energy contained in the bonds of A and B (ΔG< 0). The more negative the value of ΔG, the greater the fraction of the available AB that will be converted to A and B.

In a practical sense, we can make use of Equation (2) above to understand this process in the following way. When a large complex molecule is broken down to smaller simpler molecules, energy is released because the smaller molecules contain less energy in their chemical bonds than the complex molecule (ΔG < 0). Assuming the reaction is exothermic (ΔH< 0), this energy will be released partially as heat and partially as an increased randomness in the chemical system (ΔS > 0) and the reaction will occur spontaneously.

COUPLED REACTIONS CAPTURE ENERGY AND DRIVE "UNFAVORABLE" PROCESSES

While heat is vital to the human body, the reader may (quite correctly) suspect that the main reason we are interested in the energy released in chemical reactions such as Equation (1) is that this energy can also be captured, stored and used later to do useful work in the body. The energy of a chemical reaction is captured when an energy-releasing reaction (ΔG < 0) is "coupled" to a reaction that requires energy. Consider the coupled set of reactions below:

AB → A + B + energy ADP + P_i + energy → ATP. (3)

In these simultaneous reactions, the energy released when the complex molecule AB is broken down is immediately used to build a molecule of adenosine triphosphate (ATP) from a molecule of adenosine diphosphate (ADP) and an inorganic phosphate (P_i). ATP is a high energy compound. It is called the "energy currency" of the body because once it is formed, it provides energy that the body can "spend" later to drive vital reactions in cells (Figure 1).

ADP consists of an adenosine group bound to two phosphates, while ATP is the same molecule with a third phosphate bound. The phosphate groups have negative charges and repel each other as two magnets would if their negative poles were placed close together. Thus there is considerable energy in the bond that holds the second and third phosphates of ATP together. In the coupled reactions shown in Equation (3), the energy released from the breakdown of the chemical bonds in AB is transferred to the high-energy bond between the second and third phosphate groups of ATP.

Once a molecule of ATP is formed, it can be used by a cell to do work or to build complex molecules. Let us say that the cells require a complex molecule (XY). This molecule can be formed from its simpler parts (X and Y) in the reaction below:

X + Y → XY. (4)

However the formation of XY will not proceed spontaneously because the free energy of the product (XY) exceeds the free energy of the substrates (X and Y). We refer to the formation of XY as being an "unfavorable" process because, for Equation (4), ΔG> 0. Cells can form the XY they need only by coupling its formation to a reaction, such as the breakdown of ATP, that provides the energy required to build the chemical bonds that hold X and Y together. This process is shown in the coupled reaction below: The energy released from the breakdown of ATP has been used to drive an unfavorable process. A reaction (the formation of XY) that would not have occurred spontaneously has taken place. Of course, the amount of energy required for the formation of one molecule of XY must be less than the amount released when one ATP is broken down, otherwise the system would have gained total energy during the coupled reaction, and violated the first law of thermodynamics.

ENZYMES INCREASE THE RATE OF CHEMICAL REACTIONS

Thus far we have discussed whether a chemical reaction will occur spontaneously or only with the addition of energy. We have said nothing about the rate of chemical reactions—how fast they occur. If we need to release the energy stored in our food to power the pumping of our heart and allow us to move, we need to release that energy rapidly. We cannot afford to wait hours or days for the energy-releasing reactions to occur.

Enzymes are complex molecules, usually proteins, that speed up chemical reactions. Figure 2 illustrates in graphic form how enzymes function. To fully understand Figure 2, imagine a chemical reaction in which a part of one compound is transferred to another compound: This reaction occurs spontaneously (ΔG< 0), however it will only occur when a molecule of DE collides with a molecule of C with sufficient energy. The amount of energy that must be present in this collision is called the activation energy (E_a) of the reaction. If it is unusual for a molecule of DE to collide with a molecule of C with sufficient energy, the reaction will proceed very slowly. However, if an enzyme is present that binds both C and DE, the substrates will be brought closely together, reducing the activation energy. The rate at which products are formed will increase and the reaction will proceed more quickly in the presence of the enzyme. Note that enzymes have active sites with very specific shapes that bind substrate molecules and are not used up or altered during the reaction.

To understand activation energy, consider a boulder at the top of a hill. Imagine that the boulder has both the potential energy imparted by its position at the top of the hill and additional kinetic energy that causes it to "jiggle" randomly back and forth around its location. The potential energy of the boulder is analogous to the free energy of a chemical while the random motion is analogous to the random thermal motion that all molecules have. Just as chemical reactions with ΔG < 0 proceed spontaneously, the boulder will have a natural tendency to roll down the hill because its potential energy state is lower at the bottom of the hill than at the top. However, if there is a small rise between the boulder and the slope of the hill, the boulder must have enough "activation" energy from its random motion to get over that rise. We could increase the likelihood that the boulder will roll down the hill either by adding more kinetic energy (giving it a push) or by lowering the rise. Enzymes work by lowering the rise (activation energy).

In thermodynamic terms, a spontaneous reaction (ΔG< 0) may proceed only slowly without enzymes because of a large activation energy (E_a). Adding enzymes to the system does not change the free energy of either the substrates or products (and thus does not alter the ΔG of the reaction) but it does lower the activation energy and increase the rate of the reaction.

ANIMAL CELLS EFFICIENTLY CAPTURE THE ENERGY RELEASED DURING CATABOLISM

Animal cells obtain much of their energy from the breakdown (catabolism) of the six-carbon sugar glucose (C₆H₁₂O₆ ). The overall reaction for the catabolism of glucose is: In the presence of oxygen (O₂ ), glucose is broken down to carbon dioxide (CO₂) and water (H₂O). Energy is released because the free energy in the chemical bonds of the products is less than the free energy in the bonds of the glucose. It might seem simplest to couple the energy-liberating breakdown of glucose directly to each energy-requiring process in the body, much as the two chemical reactions in Equation (3) are coupled. However this is not practical. When glucose is broken down in a single step (such as by burning) a large amount of energy is released from every glucose molecule. If the catabolism of a glucose molecule were coupled directly to a process that required only a small amount of energy, the extra energy released from the glucose would be lost as heat. Thus, for efficiency, animal cells break glucose down by a multistep process. Cells release the energy in the bonds of the glucose molecule in a controlled way and capture this energy by using it to produce ATP. The breakdown of ATP, which releases energy in smaller amounts, is then coupled to energy-requiring reactions as in Equation (4).

The first segment of glucose catabolism is called "glycolysis." This process begins when glucose is transported into a cell. In a series of reactions within the cell, each of which requires a specific enzyme, a single six-carbon glucose molecule is converted to two molecules of pyruvic acid (three carbons each). For each molecule of glucose that undergoes glycolysis, two molecules of ADP are converted to ATP, and two molecules of nicotinamide adenine dinucleotide (NAD) accept a hydrogen atom and become NADH. The overall reaction of glycolysis is:

The discerning reader will recognize that, while Equation (8) is written correctly, it does not explain one very interesting aspect of glycolysis. In the first two steps of glycolysis, phosphate groups are donated by ATP to glucose. This may seem odd because the goal of glucose catabolism is to liberate energy in the form of ATP but these first steps actually consume ATP! These steps have an important function, however. By adding a charged (polar) phosphate group to the glucose, they make this energy-rich molecule very insoluble in the lipid (nonpolar) cell membrane trapping the glucose inside the cell.

The next steps of glucose catabolism are called the "citric acid cycle." The pyruvic acid formed in glycolysis is transported into the mitochondria, which are subcellular organelles with double (inner and outer) membranes. They are referred to as the "powerhouses" of the cell because they produce most of the ATP. Inside the mitochondria, each three-carbon pyruvic acid molecule is converted to a two-carbon molecule of acetyl-coenzyme-A (acetyl CoA). A molecule of CO₂ is released and a molecule of NADH is generated. The acetyl CoA combines with a four-carbon molecule of oxaloacetic acid, forming the six-carbon molecule citric acid. Then, via a complex set of reactions, each of which requires its own enzyme, the citric acid is reconverted to oxaloacetic acid. Additional molecules of CO₂, NADH, FADH₂ (another hydrogen atom acceptor) and ATP are formed in the process. The overall reaction of the citric acid cycle is:

The CO₂ generated when pyruvic acid is consumed in this cycle is the CO₂ product seen in Equation (7).

Thus far glucose catabolism has generated only a modest amount of ATP. It has, however, added a substantial number of hydrogen atoms to the hydrogen acceptor molecules NAD and FAD. The NADH and FADH₂ that result now pass their hydrogen atoms to a series of proteins in the mitochondrial membrane called the "electron transport system." This system splits the hydrogen atoms into a hydrogen ion (H⁺) and an electron. The electron is passed from one protein to the next down the electron transport system. With each transfer, the electron gives up some energy and the protein of the transport system uses this energy to pump hydrogen ions from inside the mitochondrion to the space between the inner and outer membranes. These hydrogen ions then reenter the inner mitochondria through special hydrogen ion channels that capture the energy released in this hydrogen ion movement and use it to convert ADP to ATP. In the final step of glucose catabolism, the hydrogen ions and electrons are combined with oxygen to form water. These are the oxygen and water molecules seen in Equation (7).

Each time NADH gives up an electron to the electron transport system enough H⁺ is pumped from the mitochondria to generate three molecules of ATP. However the energy of one ATP must be used to transport the NADH produced during glycolysis into the mitochondria, so this NADH generates a net gain of only two ATP for the cell. For each FADH₂ produced, an additional two ATP are generated. Thus, we find that for each molecule of glucose broken down the cell obtains:

• 2 ATP produced directly in glycolysis,
• 4 ATP from the 2 NADH produced in glycolysis (1 NADH per pyruvic acid),
• 24 ATP from the 8 NADH produced in the citric acid cycle (4 NADH per pyruvic acid),
• 2 ATP produced directly in the citric acid cycle, and
• 4 ATP from the 2 FADH₂ produced in the citric acid cycle (1 per pyruvic acid).

This yields a total of 36 ATP molecules produced per molecule of glucose consumed. The reader can now appreciate why it is vital that cells release the energy of glucose slowly in a multistep process rather than all at once in a single step. If glucose were broken down in a single reaction, the cell could never couple this breakdown to so many ATP-producing reactions and much energy would be lost. We can also see now why oxygen is vital to cells. In the absence of oxygen, glycolysis can proceed because the pyruvic acid generated is converted to lactic acid. (It is this lactic acid that makes muscles "burn" during heavy exercise.) This generates a small amount of ATP. However, in the absences of oxygen the electron transport system of the mitochondria backs up because it has no oxygen to accept the electrons and form water. Thus, lack of oxygen greatly reduces the ATP available to the cell and can result in cell death.

CARBOHYDRATE, FAT AND PROTEIN METABOLISM ARE CONNECTED

Both fats and proteins can also be catabolized for energy (i.e., ATP production). Dietary fats enter the bloodstream primarily as triglycerides (a three-carbon glycerol backbone and three fatty acids with sixteen or eighteen carbons in each). In cells, the fatty acids are split from the glycerol. The glycerol is converted to pyruvic acid and enters the mitochondria where it takes part in the citric acid cycle. The fatty acids undergo a process known as "beta-oxidation." During beta-oxidation, which occurs in the mitochondria, a molecule called coenzyme A is attached to the end carbon of the fatty acid chain. Then the last two carbons of the chain are cleaved with the CoA attached, producing a molecule of acetyl CoA, and a shortened fatty acid chain. This process is repeated until the entire fatty acid chain has been converted to acetyl CoA. The acetyl CoA enters the citric acid cycle. The catabolism of a single triglyceride molecule with three eighteen-carbon fatty acids yields over 450 molecules of ATP.

Dietary proteins are absorbed into the blood as amino acids, small molecules made up of a carbon backbone and a nitrogen-containing amino group (NH₂). Because protein is relatively rare and difficult to obtain, it is reasonable that the body should metabolize amino acids for energy primarily when other sources (such as sugars and fats) are unavailable. In times of great need, body cells can remove the amino group from amino acids, converting them to a form that can enter the citric acid cycle. Because muscle is made up primarily of protein, "crash" dieting causes the body to digest muscle tissue for energy.

ANIMAL CELLS USE ATP TO BUILD COMPLEX MOLECULES

Proteins are complex molecules that give cells structure and act as both enzymes and "motors" within cells. Proteins are long strings of amino acids folded in specific three-dimensional formations. There are twenty different animo acids in our bodies. DNA, the genetic material located in the cell nucleus, carries information for the order of the amino acids in each protein. Indeed, in the simplest sense, a "gene" is the section of DNA that carries the information for the construction of a single protein.

We have twenty-three pairs of chromosomes in our cells. Each chromosome is made up of a single huge molecule of DNA and contains many thousands of genes. The process by which the information in a gene instructs the cell in the formation of a protein is illustrated in Figure 3. DNA has the shape of a ladder. The ladder rungs are made up of four different molecules called "nucleotides." The information that the DNA carries is coded in the order of the ladder rungs. When a cell needs a particular protein it begins by "unzipping" the DNA ladder at the gene for that protein, exposing the information on the rungs. Then the cell makes a "messenger RNA" molecule (mRNA) that carries the same information as the gene. This process, called "transcription," requires that the cell build the messenger RNA from nucleotides. The mRNA then leaves the cell nucleus for the cell cytoplasm.

In the cytoplasm, the mRNA attaches to a ribosome and acts as a template for the construction of a protein with the proper amino acid sequence (a process known as "translation"). Single amino acids are brought to the ribosome by "transfer RNA" molecules (tRNA) and added to the growing amino acid chain in the order instructed by the mRNA. Each time a nucleotide is added to the growing RNA strand, one molecule of ATP is broken down to ADP. Each time a tRNA binds an amino acid and each time the amino acid is added to the protein, additional ATP is broken down to ADP. Because proteins can contain many hundreds of amino acids, the cell must expend the energy in 1,000 or more ATP molecules to build each protein molecule.

ANIMAL CELLS USE ATP TO DO WORK

Muscles can exert a force over a distance (i.e., do work). Thus, muscle contraction must use energy. The contractile machinery of muscle is made up of thin filaments that contain the protein "actin" and thick filaments that contain the protein "myosin" (Figure 4a). The myosin molecules have extensions known as "crossbridges" that protrude from the thick filaments. When muscle contracts, these crossbridges attach to the thin filaments at a 90-degree angle, and undergo a shape change to a 45-degree angle (power stroke) that draws the thin filaments across the thick filament. The crossbridge heads then detach, recock to 90 degrees, reattach to the thin filament and repeat the process. This entire process of myosin interaction with actin is known as the crossbridge cycle (Figure 4b).

Each time a myosin crossbridge goes through its cycle it breaks down one molecule of ATP to ADP and uses the energy released to do work. It would be easier to understand this process if the energy release of ATP breakdown occurred simultaneously with the work performing step—the power stroke; however, a careful examination of Figure 4b reveals that this is not the case. The binding of ATP to myosin allows the myosin crossbridge to detach from the actin-containing thin filament. The breakdown of ATP to ADP with its energy release occurs when the crossbridge is detached and recocks the crossbridge, readying it for another power stroke.

"Efficiency" is the ratio of work done divided by energy expended. The efficiency of muscle's conversion of the chemical energy from ATP into mechanical work depends upon the rate of muscle contraction. Imagine an isolated muscle in a laboratory contracting against a weight. If the weight is too heavy for the muscle to lift, the muscle uses energy to develop force but does no work because it cannot move the weight. (Recall that work is equal to force times distance.) Thus, for contractions in which the muscle develops force but does not move a weight (isometric contractions), the muscle has an efficiency of zero. When a muscle applies a constant force to lift a weight through a distance (isotonic contractions), energy use efficiency is greatest (about 50 percent) when the muscle is contracting at one-third its maximum velocity and falls to lower levels when the muscle contracts either faster or more slowly than this. This may seem like a great waste of energy. However, much of the energy that does not do work ultimately appears as heat. This heat may not add to the strict definition of efficiency, but it is not wasted in a biological sense because it serves to maintain our body temperature.

THE METABOLIC RATE IS THE ENERGY OUTPUT OF THE ENTIRE BODY

A "calorie" is the amount of heat energy needed to raise the temperature of one gram of water by 1 degree celsius. Because this is a very small unit compared to the energy needs of the body, we use the kilocalorie, or dietary calorie (1 kilocalorie = 1,000 calories), when discussing total body metabolism. The term "Calorie" (capitalized) refers to kilocalories. The energy output of the entire body is called the "metabolic rate." This rate, expressed as Calories expended per unit time, has several components: 1) the energy needed to maintain life at rest—the basal metabolic rate or BMR, 2) the additional energy needed to digest food, and 3) any additional energy expended to perform exercise and work.

The basal metabolic rate for adults is 1 to 1.2 Calories/minute or 60 to 72 Calories/hour. This energy powers the movement of the chest during respiration and the beating of the heart—processes that are obviously necessary for life. However, a surprisingly large fraction of the BMR is used by cells to maintain ionic gradients between their interior and the fluid that surrounds them (the interstitial fluid or tissue fluid).

The interior of all body cells has a high concentration of potassium ions (K⁺) and a low concentration of sodium ions (Na⁺). The interstitial fluid and the blood plasma have a high Na⁺ concentration and a low K⁺ concentration. When electrical signals, known as "action potentials," pass along nerves, protein channels or gates in the nerve cell membrane open and allow sodium to enter the nerve cell and potassium to leave. It is the current carried by these ionic movements that is responsible for the action potential. Once the action potential has passed, the sodium that entered the nerve cell must be pumped back out and the potassium that left must be pumped back in, both against a concentration gradient. Another protein, known as the "sodium-potassium pump" does this pumping, at substantial energy cost. The work of the sodium-potassium pump comprises a significant part of the two-fifths of the BMR resulting from activity of the brain and spinal cord.

In addition to the BMR, the body uses energy to digest and store food. Digestion requires muscular contraction for the motion of the stomach and intestines, as well as the production of digestive enzymes, many of them proteins. The storage of food energy in the form of large molecules also requires energy. For example, glucose subunits are combined and stored as the large molecule glycogen in the liver and muscle. The production of glycogen from glucose requires energy input in the form of ATP.

The energy expenditure needed to produce glycogen is worthwhile for the body because glycogen serves as a ready source of glucose during periods of low food intake and high energy output. Glycogen can be broken down to glucose 6-phosphate (glucose with a phosphate group attached, see Figure 5). In muscle, glucose 6-phosphate is broken down to pyruvic acid through glycolysis and then enters the citric acid cycle. This process provides ATP for muscle contraction (Figure 4b). In the liver, the glucose 6-phosphate is converted to glucose. Without its charged phosphate group, glucose can leave the liver cells and provide for the energy requirements of other tissues, including the brain.

Body activity also adds to the metabolic rate. In general, the more strenuous the activity, the more work is done and the greater the increase in metabolic rate. For an adult male of average size, the BMR (measured lying down) accounts for 1,500-1,600 Calories per day. If this subject sat still but upright in a chair, he would use over 2,000 Calories per day, and if he engaged in prolonged strenuous activity he might expend as much as 10,000 Calories per day. Young people generally have higher metabolic rates than do elderly individuals, partially because younger people have, on average, more muscle mass than the elderly.

The metabolic rate is increased by several hormones including thyroid hormone, adrenalin and male sex hormones. The increase in metabolic rate caused by male sex hormones explains why males have slightly higher average metabolic rates than females of the same size and age. Living in a cold climate increases the metabolic rate because the cold stimulates thyroid hormone production and this hormone increases heat output of the body, while living in a warm climate causes the metabolic rate to decrease.

Training increases the body's ability to perform physical activity. The basic structure of muscle and crossbridge cycle are not altered by training. However, performing strength exercises makes muscle stronger by adding more thick and thin filaments (and thus more crossbridges) in parallel with those that already exist. Cardiovascular training increases the number and size of the blood vessels that supply oxygen to muscles, strengthens the heart and lungs, and even increases the ability of muscle cells to produce ATP by increasing the number of mitochondria they contain. As a result, a trained athlete can achieve a much higher metabolic rate and perform far more work when they exercise than can an untrained individual.

Most physical activity includes moving the body through a distance. In general, larger animals expend less energy to move each gram of body tissue at fixed velocity than do small animals. This difference probably results from the fact that small animals need a faster rate of muscle shortening (and therefore a faster crossbridge cycle) to achieve a given velocity of motion, and means that small animals are inherently less efficient in their locomotion than are large animals. On the other hand, because small animals have less inertia and experience less drag, they can accelerate to maximum speed more quickly and with less energy expenditure than larger animals.

Different animals employ different forms of locomotion, and these forms also differ in efficiency. Most swimming animals are at or near neutral buoyancy in water, and thus do not need to expend energy working against gravity. For this reason, swimming is inherently more efficient than flying even though the swimming animal must move through a medium (water) that is much denser than air. Running is the least efficient form of locomotion because running animals (including people) move their body mass up and down against gravity with every stride.

The metabolic rate can be measured in several ways. When no external work is being performed, the metabolic rate equals the heat output of the body. This heat output can be measured by a process called direct calorimetry. In this process, the subject is placed in an insulated chamber that is surrounded by a water jacket. Water flows through the jacket at constant input temperature. The heat from the subject's body warms the air of the chamber and is then removed by the water flowing through the jacketing. By measuring the difference between the inflow and outflow water temperatures and the volume of the water heated, it is possible to calculate the subject's heat output, and thus the metabolic rate, in calories.

Another method of measuring the metabolic rate, and one that allows measurements while the subject is performing external work, is indirect calorimetry. In this process, the subject breathes in and out of a collapsible chamber containing oxygen, while the carbon dioxide in the subject's exhaled air is absorbed by a chemical reaction. The volume decrease of the chamber, equivalent to the amount of oxygen used, is recorded. Because we know the total amount of energy released in the catabolism of glucose, and the amount of oxygen required for this process (Equation 7) it is possible to calculate the metabolic rate once the total oxygen consumption for a period of time is known. Of course, our bodies are not just breaking down glucose; and other nutrients (fats and proteins) require different amounts of oxygen per Calorie liberated than does glucose. For this reason, indirect calometric measurements are adjusted for the diet of the subject.

THE BODY CAN STORE ENERGY-RICH SUBSTANCES

Our bodies must have energy available as ATP to power chemical reactions. We must also store energy for use during periods of prolonged energy consumption. When we exercise, ATP powers the myosin crossbridge cycle of muscle contraction (Figure 4b). However, our muscle cells have only enough ATP for about one second of strenuous activity. Muscle also contains a second high-energy compound called "creatine phosphate" that can give up energy to reconvert ADP to ATP by means of the coupled reactions below: Muscles contain enough creatine phosphate to power contraction for about ten seconds.

For muscle contraction to continue beyond this brief period, we must rely on the stored energy reserves of glycogen and fats. Glycogen, the storage form of carbohydrate (Figure 5), is present in muscle and liver. Even in the absence of sufficient oxygen, muscle glycogen can be broken down through glycolysis to provide enough energy for an additional five minutes of muscle contraction. When oxygen is present, the glycogen in muscle and liver provide enough energy (via the citric acid cycle) to power muscle contraction for three hours or more. The "carbo loading" athletes engage in before a marathon race (often including a large pasta dinner) is an attempt to "top off" their glycogen stores, and a depletion of glycogen may contribute to the phenomenon of "hitting the wall" in which athletic performance declines substantially after several hours of intense exercise. When glycogen stores are depleted, we must rely on fats to power muscle contraction.

In a prolonged fasting state, liver glycogen can supply glucose to the blood, and ultimately to tissues such as the brain that preferentially use glucose, for only about twelve hours, even at rest. Thereafter fat and protein stores are broken down for energy. Even people of normal weight have an average of 15 percent (for men) to 21 percent (for women) body fat. So, as long as their fluid intake is sufficient, a healthy person may survive as much as two months of fasting. However fasting has significant negative effects. Fats are broken down to glycerol and fatty acids. Glycerol is converted to glucose by the liver in a process called "gluconeogenesis," and the glucose is released into the blood to provide energy for the brain. The fatty acids are metabolized by a variety of tissues, leaving keto acids that cause the acid level in the blood to rise (fall in pH). Some protein is broken down to amino acids and these, like glycerol, takes part in gluconeogenesis. The metabolic rate falls as the body attempts to conserve energy. This reduction in metabolic rate with fasting is one reason crash dieting is so ineffective. When fat stores are used up, protein catabolism accelerates. Body muscle is digested and the person develops the stick-thin extremities characteristicsc of starving children and those with anorexia nervosa. If they do not receive nourishment, these people will soon die.

Those with a normal diet take in food in the forms of carbohydrates, fats and proteins. Because it has a low water content and produces so many ATP molecules, fat yields 9.3 Calories per gram while carbohydrates and proteins yield less than half as much (4.1 and 4.3 calories per gram respectively). Thus, we get a huge number of calories from a small quantity of fat eaten. The average person in the United States has a diet with 50 percent of the calories in the form of carbohydrates, 35 percent in the form of fat and 15 percent in the form of protein. We need about 1 gram of protein per kilogram of body weight per day to replace body proteins that are broken down. A 70 kg person on an average 5,000-Calorie per day diet receives over twice this amount (5,000 Calories per day × 0.15 of Calories as protein/4.3 Calories per gram of protein = 174 grams of protein per day). Thus, most of us are in little danger of protein deficiency. Most of us would probably be healthier if we ate less fat as well. A high fat diet is a known risk factor for diseases of the heart and blood vessels, as well as for colon cancer. Because autopsies on young otherwise healthy soldiers killed in combat indicate that fatty deposits in arteries can be well established by twenty years of age, it is never too early to begin reducing fat intake. A modest goal might to have no more than 30 percent of dietary calories from fat. However, studies from cultures where people consume little red meat indicate that it is possible, and almost certainly healthy, to reduce our fat intake far more than this.

We have seen that energy flow in the body's chemical reactions follows the same basic rules as does energy change in nonliving systems. Energy is taken in as food, then either stored as fat or glycogen, or released in an orderly manner through a multistep enzyme-controlled process and converted to ATP. The ATP is then used to synthesize large molecules needed by the body and to power body processes that do work. The body's overall metabolic rate can be measured and is affected by a variety of internal and external factors. Diet affects the body's energy stores, and insufficient or excess food intake influences metabolic processes. We can use an understanding of metabolism to match our food intake to our body needs and in so doing to maximize our health.

David E. Harris

See also: Biological Energy Use, Ecosystem Functioning of.

BIBLIOGRAPHY

Berne, R. M., and Levy, M. N. (1998). Physiology, 4th ed. Boston, MA: Mosby Year Book.

Eckert, R.; Randall, D.; and Augustine, G. (1988). Animal Physiology, 3rd ed. New York, NY: W. H. Freeman and Company.

Guyton, A. C., and Hall, J. E. (1996). Textbook of Medical Physiology, 9th ed. Philadelphia, PA: W. B. Saunders Company.

Marieb, E. N. (1999). Human Anatomy & Physiology, 5th ed. Reading, MA: Benjamin/Cummings Publishing Company.

Martini, F. M. (1998). Fundamentals of Anatomy & Physiology, 4th ed. Upper Saddle River, NJ: Prentice-Hall.

Schmidt-Nielsen, K. (1997). Animal Physiology, 5th ed. Cambridge, England: Cambridge University Press.

Segel, I. H. (1976). Biochemical Calculations, 2nd ed. New York, NY: John Wiley & Sons.

Woledge, R. C.; Curtin, N. A.; and Homsher, E. (1985). Energetic Aspects of Muscle Contraction. Monographs of the Physiology Society, No. 41. Boston, MA: Academic Press.