Chapter 5 - The Working Cell PDF

# Chapter 5: The Working Cell ## The Working Cell The illustration below is beautiful and intriguing-but what does it represent? This computer model shows a small section of a membrane in a human cell; notice the water molecules (depicted with red and gray balls) streaming single file across the m...

# Chapter 5: The Working Cell ## The Working Cell The illustration below is beautiful and intriguing-but what does it represent? This computer model shows a small section of a membrane in a human cell; notice the water molecules (depicted with red and gray balls) streaming single file across the membrane. Notice also the phospho-lipids that make up the lipid bilayer of this membrane: The yellow balls represent the phosphate heads and the green squiggles are the fatty acid tails of the phospholipids. The blue ribbons embedded in the membrane represent regions of a membrane protein called aquaporin that function as water channels. Just one molecule of this protein enables billions of water molecules to flow through the membrane every second-many more than could wander through the lipid bilayer on their own. Aquaporins are common in cells involved in water balance. For example, your kidneys must filter and reabsorb many liters of water a day, and aquaporins are vital to their proper functioning. There are rare cases of people with defective aquaporins whose kidneys can't reabsorb water and must drink 20 liters of water every day to prevent dehydration. On the other hand, if kidney cells have too many aquaporins, excess water is reabsorbed and body tissues may swell. A common complication of pregnancy is fluid retention, and it is likely caused by increased synthesis of aquaporin proteins. Later in the chapter you will learn about the serendipitous discovery of these water channels. ## How can water flow through a membrane? * Water molecules diffuse through the lipid bilayer * Water molecules moves across the membrane with the help of aquaporins ### Big Ideas **Membrane Structure and Function (5.1-5.9)** A cells membrane's structure enables it's function such as regulation of traffic across the membrane. **Energy and the Cell (5.10-5.12)** A cell's metabolic reaction transform energy, using ATP to drive cellular work. **How Enzymes Function (5.13-5.16)** Enzymes speed up a cell's chemical reactions and provide precise control of metabolism. ## Membrane Structure and Function ### 5.1 Membranes are fluid mosaics of lipids and proteins with many functions Biologists use the fluid mosaic model to describe a membrane's structure-diverse protein molecules suspended in a fluid phospholipid bilayer. This module illustrates the structure and function of a plasma membrane, the boundary that encloses a living cell. Like all cellular membranes, the plasma membrane exhibit selective permeability; that is, it allows some substances to cross more easily than others. But the plasma membrane does more than just regulate the exchange of materials. This figure will help you visualize all the activity taking place in and across the membranes of two adjacent cells. **Diverse functions of the plasma membrane** * **Small nonpolar molecules may diffuse across the lipid bilayer** * **Some membrane proteins are enzymes, which may be grouped to carry out sequential reactions** * **Membrane proteins may form intercellular junctions that attach adjacent cells.** * **Proteins that attach to the extracellular matrix and cytoskeleton help support the membrane and can coordinate external and internal changes** * **Signaling molecules bind to receptor proteins, which relay the message by activating other molecules inside the cell.** * **Transport proteins allow specific ions or to enter or exit the cell.** * **Glycoproteins may serve as ID tags that are recognized by membrane proteins of other cells.** **What makes this membrane a mosaic?** Note the diverse proteins, each with a specific function. ### 5.2 The spontaneous formation of membranes was a critical step in the origin of life Phospholipids, the key ingredients of biological membranes, were probably among the first organic molecules that formed from chemical reactions on early Earth. These lipids could spontaneously self-assemble into simple membranes, as can be demonstrated in a test tube. When a mixture of phospholipids and water is shaken, the phospholipids organize into bilayers surrounding water-filled bubbles. This assembly requires neither genes nor other information beyond the properties of the phospholipids themselves. The formation of membrane-enclosed collections of molecules would have been a critical step in the evolution of the first cells. A membrane can enclose a solution that is different in composition from its surroundings. A plasma membrane that allows cells to regulate their chemical exchanges with the environment is a basic requirement for life. Indeed, all cells are enclosed by a plasma membrane that is similar in structure and function-illustrating the evolutionary unity of life. **In the origin of a cell, why would the formation of a simple lipid bilayer membrane not be sufficient? What else would have to be part of such a membrane?** ### 5.3 Passive transport is diffusion across a membrane with no energy investment Molecules have a type of energy called thermal energy, due to their constant motion. One result of this motion is diffusion, the tendency for particles of any substance to spread out into the available space. How might diffusion affect the movement of substances into or out of a cell? The figures to the right will help you visualize diffusion across a membrane. Figure 5.3A shows a solution of green dye separated from pure water by an artificial membrane. Assume that this membrane has microscopic pores through which dye molecules can move. Thus, we say the membrane is permeable to the dye. Although each molecule moves randomly, there will be a net movement from the side of the membrane where dye molecules are more concentrated to the side where they are less concentrated. Put another way, the dye diffuses down its concentration gradient. Eventually, the solutions on both sides will have equal concentrations of dye. At this dynamic equilibrium, molecules still move back and forth, but there is no net change in concentration on either side of the membrane. Figure 5.3B illustrates the important point that two or more substances diffuse independently of each other; that is, each diffuses down its own concentration gradient. Because a cell does not have to do work when molecules diffuse across its membrane, such movement across a membrane is called passive transport. Much of the traffic across cell membranes occurs by diffusion. For example, diffusion down concentration gradients is the sole means by which oxygen, essential for metabolism, enters your cells and carbon dioxide, a metabolic waste, passes out of them. Both O2 and CO2 are small, nonpolar molecules that diffuse easily across the phospholipid bilayer of a membrane. But can ions and polar molecules also diffuse across the hydrophobic interior of a membrane? They can if they are moving down their concentration gradients and if they have transport proteins to help them cross. **Why is diffusion across a membrane called passive transport?** ### 5.4 Osmosis is the diffusion of water across a membrane One of the most important substances that crosses membranes by passive transport is water. In the next module, we consider the critical balance of water between a cell and its environment. But first let's explore a physical model of the diffusion of water across a selectively permeable membrane, a process called osmosis. Remember that a selectively permeable membrane allows some substances to cross more easily than others. The top of Figure 5.4 shows what happens if a membrane permeable to water but not to a solute (such as glucose) separates two solutions that have different concentrations of solute. (A solute is a substance that dissolves in a liquid solvent. The resulting mixture is a solution.) The solution on the right side initially has a higher concentration of solute than that on the left. As you can see, water crosses the membrane until the solute concentrations are more nearly equal on both sides. In the close-up view at the bottom of Figure 5.4, you can see what happens at the molecular level. Polar water molecules cluster around hydrophilic (water-loving) solute molecules. The effect is that on the right side, there are fewer water molecules that are free to cross the membrane. The less concentrated solution on the left has fewer solute molecules but more free water molecules available to move. There is a net movement of water down its own concentration gradient, from the solution with more free water molecules (and lower solute concentration) to that with fewer free water molecules (and higher solute concentration). The result of this water movement is the difference in water levels you see at the top right of Figure 5.4. Let's now apply to living cells what we have learned about osmosis in artificial systems. **Indicate the direction of net water movement between two solutions-a 0.5% sucrose solution and a 2% sucrose solution-separated by a membrane not permeable to sucrose.** ### 5.5 Water balance between cells and their surroundings is crucial to organisms Biologists use a special vocabulary to describe how water will move between a cell and its surroundings. The term tonicity refers to the ability of a surrounding solution to cause a cell to gain or lose water. The tonicity of a solution mainly depends on its concentration of solutes relative to the concentration of solutes inside the cell. Figure 5.5, on the facing page, illustrates the effects of placing animal and plant cells in solutions of various tonicities. When an animal cell, such as the red blood cell shown in the top center of the figure, is immersed in a solution that is isotonic to the cell (iso, same, and tonos, tension), the cell's volume remains constant. The solute concentration of a cell and its isotonic environment are essentially equal, and the cell gains water at the same rate that it loses it. In your body, red blood cells are transported in the isotonic plasma of the blood. Intravenous (IV) fluids administered in hospitals must also be isotonic to blood cells. The body cells of most animals are bathed in an extracellular fluid that is isotonic to the cells. And seawater is isotonic to the cells of many marine animals, such as sea stars and crabs. What happens when an animal cell is placed in a hypotonic solution (hypo, below), a solution with a solute concentration lower than that of the cell? As shown in the upper left of the figure, the cell gains water, swells, and may burst (lyse) like an overfilled balloon. The upper right shows the opposite case-an animal cell placed in a hypertonic solution (hyper, above), a solution with a higher solute concentration. In which direction will water move? The cell shrivels and can die from water loss. For an animal to survive in a hypotonic or hypertonic environment, it must have a way to prevent excessive uptake or loss of water and regulate the solute concentration of its body fluids. The control of water balance is called osmoregulation. For example, a freshwater fish, which lives in a hypotonic environment, takes up water by osmosis across the cells of its gills. Its kidneys work constantly to remove excess water from the body. (We will discuss osmoregulation further in Module 25.4.) Water balance issues are somewhat different for the cells of plants, prokaryotes, and fungi because of their cell walls. As shown in the bottom of Figure 5.5, in a hypotonic environment a plant cell is turgid (very firm), which is the healthy state for most plant cells. Although the plant cell swells as water enters by osmosis, the cell wall exerts a back pressure, called turgor pressure, which prevents the cell from taking in too much water and bursting. Plants that are not woody, such as most houseplants, depend on their turgid cells for mechanical support. In contrast, when a plant cell is surrounded by an isotonic solution, there is no net movement of water into the cell, and the cell is flaccid (limp). In a hypertonic environment (bottom right), a plant cell is no better off than an animal cell. As a plant cell loses water, it shrivels, and its plasma membrane pulls away from the cell wall. This process, called plasmolysis, causes the plant to wilt and can be lethal to the cell and the plant. The walled cells of bacteria and fungi also plasmolyze in hypertonic environments. Thus, meats and other foods can be preserved with concentrated salt solutions because the cells of food-spoiling bacteria or fungi become plasmolyzed and eventually die. In the next module, we explore how water and other polar solutes move across cell membranes. **Explain the function of the contractile vacuoles in a freshwater Paramecium (shown in Figure 4.11A) in terms of what you have just learned about water balance in cells.** ### 5.6 Transport proteins can facilitate diffusion across membranes Recall that nonpolar molecules, such as O2 and CO2, can dissolve in the lipid bilayer of a membrane and diffuse through it with ease. But how do polar or charged substances make it past the hydrophobic center of a membrane? Hydrophilic molecules and ions require the help of specific transport proteins to move across a membrane. This assisted transport, called facilitated diffusion, is a type of passive transport because it does not require energy. As in all passive transport, the driving force is the concentration gradient. Figure 5.6 shows a common type of transport protein, which provides a channel that specific molecules or ions use as a passageway through a membrane. Another type of transport protein binds its passenger, changes shape, and releases the transported molecule on the other side. In both cases, the transport protein helps a specific substance diffuse across the membrane down its concentration gradient and, thus, requires no input of energy. Substances that use facilitated diffusion for crossing cell membranes include a number of sugars, amino acids, ions-and even water. The water molecule is very small, but because it is polar, its diffusion through a membrane's hydrophobic interior is relatively slow. For many cells, this slow diffusion of water is adequate. Cells such as plant cells, red blood cells, and the cells lining your kidney tubules, however, have greater water-permeability needs. As you saw in the chapter introduction, the very rapid diffusion of water into and out of such cells is made possible by a protein channel called an aquaporin. In the next module, we explore the discovery of these transport proteins. **How do transport proteins contribute to a membrane's selective permeability?** ### 5.7 Research on another membrane protein led to the discovery of aquaporins Sometimes major advances in science occur when a scientist is studying something else but makes the wise decision to explore an unexpected finding. Peter Agre received the 2003 Nobel Prize in Chemistry for this sort of discovery of aquaporins. In an interview, Dr. Agre described his research that led to this discovery: "When I joined the faculty at the Johns Hopkins School of Medicine, I began to study the Rh blood antigens. Rh is of medical importance...when Rh-negative mothers have Rh-positive babies. Membrane-spanning proteins are really messy to work with. But we worked out a method to isolate the Rh protein. Our sample seemed to consist of two proteins, but we were sure that the smaller one was just a breakdown product of the larger one. We were completely wrong." Dr. Agre's research team made antibodies that would specifically bind to and label this smaller protein. They found two interesting results: The antibody did not bind to any part of the Rh protein, indicating that the smaller protein wasn't part of the Rh protein. And the antibody did bind in huge quantities to red blood cells, showing that this new protein is one of the most abundant proteins in red cell membranes. Agre and his team also determined that the protein was identical to and even more abundant in certain kidney cells. But they didn't know what this protein did. A colleague suggested that the protein might be the elusive water channel that physiologists had predicted would explain the rapid transport of water in some cells. To test this hypothesis, the researchers injected messenger RNA for the protein into frog eggs, whose plasma membranes are known to be quite water impermeable. Biochemical tests showed that within 72 hours, the frog egg cells had translated the mRNA into the new protein. They transferred a group of RNA-injected frog eggs and a control group of eggs injected with only a buffer solution to a hypotonic solution and monitored the eggs with videomicroscopy. The osmotic swelling of RNA-injected and control cells is plotted in Figure 5.7. The experimental egg cells exploded in three minutes; the control eggs showed minimal swelling, even for time periods exceeding an hour. The researchers concluded that the newly discovered protein enabled the rapid movement of water into the cells. **How can water flow through a membrane?** Since the results of that experiment were reported in 1992, much research has been done on aquaporins, determining their structure and dynamic functioning. The chapter introduction presented a model of aquaporin structure. Molecular biophysicists have produced computer simulations that show water molecules flipping their way single file through an aquaporin. Such simulations have revealed how aquaporins allow only water molecules to pass through them. Aquaporins have been found in bacteria, plants, and animals, and evolutionary biologists are tracing the relationships of these various aquaporins. Medical researchers study the function and occasional malfunction of aquaporins in the human kidney, lungs, brain, and lens of the eye. The serendipitous discovery of aquaporins has led to a broad range of scientific research. **Why are aquaporins important in kidney cells?** ### 5.8 Cells expend energy in the active transport of a solute In active transport, a cell must expend energy to move a solute against its concentration gradient-that is, across a membrane toward the side where the solute is more concentrated. The energy molecule ATP (described in more detail in Module 5.12) supplies the energy for most active transport. Active transport allows a cell to maintain internal concentrations of small molecules and ions that are different from concentrations in its surroundings. For example, the inside of an animal cell has a higher concentration of potassium ions (K+) and a lower concentration of sodium ions (Na+) than the solution outside the cell. The generation of nerve signals depends on these concentration differences, which a transport protein called the sodium-potassium pump maintains by actively moving Na+ out of the cell and K+ into the cell. Figure 5.8 shows a simple model of an active transport system that pumps a solute out of the cell against its concentration gradient. The process begins when solute molecules on the cytoplasmic side of the plasma membrane attach to specific binding sites on the transport protein. With energy provided by ATP, the transport protein changes shape in such a way that the solute is released on the other side of the membrane. The transport protein returns to its original shape, ready for its next passengers. **Cells actively transport Ca2+ out of the cell. Is calcium more concentrated inside or outside of the cell? Explain.** ### 5.9 Exocytosis and endocytosis transport large molecules across membranes So far, we've focused on how water and small solutes enter and leave cells. The story is different for large molecules. A cell uses the process of exocytosis (from the Greek exo, outside, and kytos, cell) to export bulky materials such as proteins or polysaccharides. A transport vesicle filled with macromolecules buds from the Golgi apparatus and moves to the plasma membrane (see Figure 4.12). Once there, the vesicle fuses with the plasma membrane, and the vesicle's contents spill out of the cell when the vesicle membrane becomes part of the plasma membrane. For example, the cells in your pancreas that manufacture the hormone insulin secrete it into the extracellular fluid by exocytosis, where it is picked up by the bloodstream. Endocytosis (endo, inside) is a transport process through which a cell takes in large molecules. Figure 5.9 shows two kinds of endocytosis. The top diagram illustrates phagocytosis, or “cellular eating." A cell engulfs a particle by wrapping extensions called pseudopodia around it and packaging it within a membrane-enclosed sac called a vacuole. The vacuole then fuses with a lysosome, whose hydrolytic enzymes digest the contents of the vacuole (see Figure 4.10A). Protists such as amoeba take in food particles this way, and some of your white blood cells engulf invading bacteria via phagocytosis. The bottom diagram illustrates receptor-mediated endocytosis, which enables a cell to acquire specific solutes. Receptor proteins for specific molecules are embedded in regions of the membrane that are lined by a layer of coat proteins. The plasma membrane indents to form a coated pt, whose receptor proteins pick up particular molecules from the extracellular fluid. The coated pit pinches closed to form vesicle, which then releases the molecules into the cytoplasm. Your cells use receptor-mediated endocytosis to take in cholesterol from the blood for synthesis of membranes and as a precursor for other steroids. Cholesterol circulates in the blood in particles called low-density lipoproteins (LDLs). LDLs bind to receptor proteins and then enter cells by endocytosis. In humans with the inherited disease familial hypercholesterolemia, LDL receptor proteins are defective or missing. Cholesterol accumulates to high levels in the blood, leading to atherosclerosis, the buildup of fatty deposits in the walls of blood vessels (see Module 9.11). **As a cell grows, its plasma membrane expands. Does this involve endocytosis or exocytosis? Explain.** ## Energy and the Cell ### 5.10 Cells transform energy as they perform work The title of this chapter is “The Working Cell." But just what type of work does a cell do? You just learned that a cell can actively transport substances across membranes. The cell also builds those membranes and the proteins embedded in them. A cell is a miniature chemical factory in which thousands of reactions occur within a microscopic space. Some of these reactions release energy; others require energy. But before you can understand how the cell works, you must have a basic knowledge of energy. **Forms of Energy** Energy is the capacity to cause change or to perform work. There are two basic forms of energy: kinetic energy and potential energy. Kinetic energy is the energy of motion. Moving objects can perform work by transferring motion to other matter. For example, the movement of your legs can push bicycle pedals, turning the wheels and moving you and your bike up a hill. Thermal energy is a type of kinetic energy associated with the random movement of atoms or molecules. Thermal energy in transfer from one object to another is called heat. Light, which is also a type of kinetic energy, can be harnessed to power photosynthesis. **Potential energy**, the second main form of energy, is energy that matter possesses as a result of its location or structure. Water behind a dam and you on your bicycle at the top of a hill possess potential energy. Molecules possess potential energy because of the arrangement of electrons in the bonds between their atoms. **Chemical energy** is the potential energy available for release in a chemical reaction. Chemical energy is the most important type of energy for living organisms; it is the energy that can be transformed to power the work of the cell. **Energy Transformations** The study of energy transformations that occur in a collection of matter is called thermodynamics. Scientists use the word system for the matter under study and refer to the rest of the universe-everything outside the system-as the surroundings. A system can be an electric power plant, a single cell, or the entire planet. An organism is an open system; that is, it exchanges both energy and matter with its surroundings. **The first law of thermodynamics**, also known as the law of energy conservation, states that the energy in the universe is constant. Energy can be transferred and transformed, but it cannot be created or destroyed. A power plant does not create energy; it merely converts it from one form (such as the energy stored in coal) to the more convenient form of electricity. A plant cell converts light energy to chemical energy; the plant cell, too, is an energy transformer, not an energy producer. If energy cannot be destroyed, then why can't organisms simply recycle their energy? It turns out that during every transfer or transformation, some energy becomes unavailable to do work-it is converted to thermal energy (random molecular motion) and released as heat. Scientists use a quantity called entropy as a measure of disorder, or randomness. The more randomly arranged a collection of matter is, the greater its entropy. According to the second law of thermodynamics, energy conversions increase the entropy (disorder) of the universe. Figure 5.10 compares a car and a cell to show how energy can be transformed and how entropy increases as a result. Automobile engines and cells use the same basic process to make the chemical energy of their fuel available for work. The engine mixes oxygen with gasoline in an explosive chemical reaction that pushes the pistons, which eventually move the wheels. The waste products emitted from the exhaust pipe are carbon dioxide and water, energy-poor, simple molecules. Only about 25% of the energy stored in gasoline is converted to the kinetic energy of the car's movement; the rest is lost as heat. Cells also use oxygen in reactions that release energy from fuel molecules. In the process called cellular respiration, the chemical energy stored in organic molecules is used to produce ATP, which the cell can use to perform work. Just like for the car, the waste products are carbon dioxide and water. Cells are more efficient than cars, however, converting about 34% of the chemical energy in their fuel to energy for cellular work. The other 66% generates heat, which explains why vigorous exercise makes you so warm. According to the second law of thermodynamics, energy transformations result in the universe becoming more disordered. How, then, can we account for biological order? Although the intricate structures of a cell correspond to a decrease in entropy, their production is accomplished at the expense of ordered forms of matter and energy taken in from the surroundings. As shown in Figure 5.10, cells extract the chemical energy of glucose and return disordered heat and lower-energy carbon dioxide and water to the surroundings. In a thermodynamic sense, a cell is an island of low entropy in an increasingly random universe. **How does the second law of thermodynamics explain the diffusion of a solute across a membrane?** ### 5.11 Chemical reactions either release or store energy Chemical reactions are of two types: exergonic or endergonic. An exergonic reaction releases energy (exergonic means "energy outward"). As Figure 5.11A shows, an exergonic reaction begins with reactants whose covalent bonds contain more potential energy than those in the products. The reaction releases to the surroundings an amount of energy equal to the difference in potential energy between the reactants and the products. Consider what happens when wood burns. One of the major components of wood is cellulose, a large energy-rich carbohydrate composed of many glucose monomers. Burning wood releases the energy of glucose as heat and light. Carbon dioxide and water are the products of the reaction. As you learned in Module 5.10, cells release energy from fuel molecules in the process called cellular respiration. Burning and cellular respiration are alike in being exergonic. They differ in that burning is essentially a one-step process that releases all of a substance's energy at once. Cellular respiration, on the other hand, involves many steps, each a separate chemical reaction; you can think of it as a “slow burn." Some of the energy released by cellular respiration escapes as heat, but a substantial amount is stored in ATP, the immediate source of energy for a cell. Endergonic reactions require a net input of energy and yield products that are rich in potential energy (endergonic means "energy inward"). As shown in Figure 5.11B, an endergonic reaction starts with reactants that contain relatively little potential energy. Energy is absorbed from the surroundings as the reaction occurs, so the products of an endergonic reaction contain more chemical energy than the reactants did. Photosynthesis, the process by which plant cells make sugar, is an example of an endergonic process. Photosynthesis starts with energy-poor reactants (carbon dioxide and water molecules) and, using energy absorbed from sunlight, produces energy-rich sugar molecules. Living cells carry out thousands of exergonic and endergonic reactions. The total of an organism's chemical reactions is called metabolism. We can picture a cell's metabolism as a road map of thousands of chemical reactions arranged as intersecting highways or metabolic pathways. A metabolic pathway is a series of chemical reactions that either builds a complex molecule or breaks down a complex molecule into simpler compounds. The “slow burn” of cellular respiration is an example of a metabolic pathway in which a sequence of reactions slowly releases the potential energy stored in sugar. All of an organism’s activities require energy, which is obtained from sugar and other molecules by the exergonic reactions of cellular respiration. Cells then use that energy in endergonic reactions to make molecules and do the work of the cell. Energy coupling-the use of energy released from exergonic reactions to drive endergonic reactions-is crucial in all cells. ATP molecules are the key to energy coupling. In the next module, we explore the structure and function of ATP. **Cellular respiration is an exergonic process. Remembering that energy must be conserved, what do you think becomes of the energy extracted from food during this process?** ### 5.12 ATP drives cellular work by coupling exergonic and endergonic reactions ATP powers nearly all forms of cellular work. The abbreviation ATP stands for adenosine triphosphate, and as Figure 5.12A shows, ATP consists of an organic molecule called adenosine and a triphosphate tail of three phosphate groups (each symbolized by P). All three phosphate groups are negatively charged. These like charges are crowded together, and their mutual repulsion makes the triphosphate tail of ATP the chemical equivalent of a compressed spring. As a result, the bonds connecting the phosphate groups are unstable and can readily be broken by hydrolysis, the addition of water. Notice in Figure 5.12A that when the bond to the third group breaks, a phosphate group leaves ATP—which becomes ADP (adenosine diphosphate)—and energy is released. Thus, the hydrolysis of ATP is exergonic-it releases energy. How does a cell couple this reaction to an endergonic (energy-requiring) reaction? It usually does so by transferring a phosphate group from ATP to another molecule. This phosphate transfer is called phosphorylation, and most cellular work depends on ATP energizing molecules by phosphorylating them. **What types of work does a cell do?** As Figure 5.12B shows, the chemical, transport, and mechanical work of a cell are all driven by ATP. In chemical work, the phosphorylation of reactants provides energy to drive the endergonic synthesis of products. In transport work, ATP drives the active transport of solutes across a membrane against their concentration gradients by phosphorylating transport proteins. And in an example of mechanical work, the transfer of phosphate groups to special motor proteins in muscle cells causes the proteins to change shape and pull on other protein filaments, in turn causing the cells to contract. ATP is a renewable resource. A cell uses and regenerates ATP continuously. Figure 5.12C shows the ATP cycle. Each side of this cycle illustrates energy coupling. Energy released in exergonic reactions, such as the breakdown of glucose during cellular respiration, is used to generate ATP from ADP. In this endergonic process, a phosphate group is bonded to ADP, forming ATP. The hydrolysis of ATP releases energy that drives endergonic reactions. The ATP cycle runs at an astonishing pace. In fact, a working muscle cell may consume and regenerate 10 million ATP molecules each second. **Explain how ATP transfers energy from exergonic to endergonic processes in the cell.** ### 5.13 Enzymes speed up the cell's chemical reactions by lowering energy barriers Your room gets messier; water flows downhill; sugar crystals dissolve in your coffee. Ordered structures tend toward disorder, and high-energy systems tend to change toward a more stable state of low energy. Proteins, DNA, carbohydrates, lipids-most of the complex molecules of your cells are rich in potential energy. Why don’t these high-energy, ordered molecules spontaneously break down into less ordered, lower-energy molecules? They remain intact for the same reason that wood doesn't normally burst into flames or the gas in an automobile's gas tank doesn't spontaneously explode. There is an energy barrier that must be overcome before a chemical reaction can begin. Energy must be absorbed to contort or weaken bonds in reactant molecules so that they can break and new bonds can form. We call this the activation energy (because it activates the reactants). We can think of activation energy as the amount of energy needed for reactant molecules to move “uphill” to a higher-energy, unstable state so that the "downhill" part of a reaction can begin. The activation energy barrier protects the highly ordered molecules of your cells from spontaneously breaking down. But now we have a dilemma. Life depends on countless chemical reactions that constantly change a cell’s molecular makeup. Most of the essential reactions of metabolism must occur quickly and precisely for a cell to survive. How can the specific reactions that a cell requires get over that energy barrier? One way to speed reactions is to add heat. Heat speeds up molecules and agitates atoms so that bonds break more easily and reactions can proceed. Certainly, adding a match to kindling will start a fire, and the firing of a spark plug ignites gasoline in an engine. But heating a cell would speed up all chemical reactions, not just the necessary ones, and too much heat would kill the cell. The answer to this dilemma lies in enzymes-molecules that function as biological catalysts, increasing the rate of a reaction without being consumed by the reaction. Almost all enzymes are proteins. (Some RNA molecules can also function as enzymes.) An enzyme speeds up a reaction by lowering the activation energy needed for a reaction to begin. Figure 5.13 compares a reaction without an enzyme (left) and with an enzyme (right). Notice how much easier it is for the reactant to get over the activation energy barrier when an enzyme is involved. In the next module, we explore how the structure of an enzyme enables it to lower the activation energy, allowing a reaction to proceed. **The graph below illustrates the course of a reaction with and without an enzyme. Which curve represents the enzyme-catalyzed reaction? What energy changes are represented by the lines labeled a, b, and c?** ### 5.14 A specific enzyme catalyzes each cellular reaction You just learned that an enzyme catalyzes a reaction by lowering the activation energy barrier. How does it do that? With the aid of an enzyme, the bonds in a reactant are contorted into the higher-energy, unstable state from which the reaction can proceed. Without an enzyme, the activation energy barrier might never be breached. For example, a solution of sucrose (table sugar) can sit for years at room temperature with no appreciable hydrolysis into its components glucose and fructose. But if we add a small amount of the enzyme sucrase, all the sucrose will be hydrolyzed within seconds. An enzyme is very selective in the reaction it catalyzes. As a protein, an enzyme has a unique three-dimensional shape, and that shape determines the enzyme's specificity. The specific reactant that an enzyme acts on is called the enzyme's substrate. A substrate fits into a region of the enzyme called the active site-typically a pocket or groove on the surface of the enzyme. Enzymes are specific because only specific substrate molecules fit into their active sites. **The Catalytic Cycle** Figure 5.14 illustrates the catalytic cycle of an enzyme. Our example is the enzyme sucrase, which catalyzes the hydrolysis of sucrose. (Most enzymes have names that end in -ase, and many are named for their substrate.) 1 The enzyme starts with an empty active site. 2 Sucrose enters the active site, attaching by weak bonds. The active site changes shape slightly, embracing the substrate more snugly, like a firm handshake. This induced fit may contort substrate bonds or place chemical groups of the amino acids making up the active site in position to catalyze the reaction. (In reactions involving two or more reactants, the active site holds the substrates in the proper orientation for a reaction to occur.) 3 The strained bond of sucrose reacts with water, and the substrate is converted (hydrolyzed) to the products glucose and fructose. 4 The enzyme releases the products and emerges unchanged from the reaction. Its active site is now available for another substrate molecule, and another round of the cycle can begin. A single enzyme molecule may act on thousands or even millions of substrate molecules per second. **Optimal Conditions for Enzymes** As with all proteins, an enzyme's shape is central to its function, and this three-dimensional shape is affected by the environment. For every enzyme, there are optimal conditions under which it is most effective. Temperature, for instance, affects molecular motion, and an enzyme's optimal temperature produces the highest rate of contact between reactant molecules and the enzyme's active site. Higher temperatures denature the enzyme, altering its specific shape and destroying its function. Most human enzymes work best at 35-40°C. Prokaryotes that live in hot springs, however, contain enzymes with optimal temperatures of 70°C or higher. Scientists make use of the enzymes of these bacteria in a technique that rapidly replicates DNA sequences from small samples (see Module 12.12). The optimal pH for most enzymes is near neutrality, in the range of 6-8. There are exceptions, of course. Pepsin, a digestive enzyme in your stomach, works best at pH 2. Such an environment would denature most enzymes, but the structure of pepsin is most stable and active in this acidic environment. **Cofactors** Many enzymes require nonprotein helpers called cofactors, which bind to the active site and function in catalysis. The cofactors of some enzymes are inorganic, such as the ions of zinc, iron, and copper. If the cofactor is an organic molecule, it is called a coenzyme. Most vitamins are important in nutrition because they function as coenzymes or raw materials from which coenzymes are made. For example, folic acid is a coenzyme for a number of enzymes involved in the synthesis of nucleic acids. Chemical chaos would result if all of a cell’s metabolic pathways were operating simultaneously. A cell must tightly control when and where its various enzymes are active. It does this either by switching on or off the genes that encode specific enzymes (as you will learn in Chapter 11) or by regulating the activity of enzymes once they are made. We explore this second mechanism in the next module. **Explain how an enzyme speeds up a specific reaction.** ### 5.15 Enzyme inhibition can regulate enzyme activity in a cell A chemical that interferes with an enzyme's activity is called an inhibitor. Scientists have learned a great deal about enzyme function by studying the effects of such chemicals. Some inhibitors resemble the enzyme's normal substrate and compete for entry into the active site. As shown in the lower left of Figure 5.15A, such a competitive inhibitor reduces an enzyme's productivity by blocking substrate molecules from entering the active site. Competitive inhibition can be overcome by increasing the concentration of the substrate, making it more likely that a substrate molecule rather than an inhibitor will be nearby when an active site becomes vacant. In contrast, a non