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section, you will be able to: • How do electrochemical gradients affect the active transport of ions and molecules across membranes? Connection for AP® Courses If a substance must move into the cell against its concentration gradient, the cell must use free energy, often provided by ATP, and carrier proteins acting as pumps to move the substance. Substances that move across membranes by this mechanism, a process called active transport, include ions, such as Na+ and K+. The combined gradients that affect movement of an ion are its concentration gradient and its electrical gradient (the difference in charge across the membrane); together these gradients are called the electrochemical gradient. To move substances against an electrochemical gradient This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 213 requires free energy. The sodium-potassium pump, which maintains electrochemical gradients across the membranes of nerve cells in animals, is an example of primary active transport. The formation of H+ gradients by secondary active transport (co-transport) is important in cellular respiration and photosynthesis and moving glucose into cells. Information presented and the examples highlighted in the section support concepts and learning objectives outlined in Big Idea 2 of the AP® Biology Curriculum Framework. The learning objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A learning objective merges required content with one or more of the seven science practices (SP). Big Idea 2 Enduring Understanding 2.B Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and dynamic homeostasis require that cells create and maintain internal environments that are different from their external environments. Essential Knowledge 2.B.2 Growth and dynamic homeostasis are maintained by the constant movement of molecules across membranes. Science Practice Learning Objective 1.4 The student can use representations and models to analyze situations or solve problems qualitatively and quantitatively. 2.12 The student is able to use representations and models to analyze situations or solve problems qualitatively and quantitatively to investigate whether dynamic homeostasis is maintained by the active movement of molecules across membranes. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.
10][APLO 2.17][APLO 1.2][APLO 3.24] Active transport mechanisms require the use of the cell’s energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient—that is, if the concentration of the substance inside the cell is greater than its concentration in the extracellular fluid (and vice versa)—the cell must use energy to move the substance. Some active transport mechanisms move small-molecular weight materials, such as ions, through the membrane. Other mechanisms transport much larger molecules. Electrochemical Gradient We have discussed simple concentration gradients—differential concentrations of a substance across a space or a membrane—but in living systems, gradients are more complex. Because ions move into and out of cells and because cells contain proteins that do not move across the membrane and are mostly negatively charged, there is also an electrical gradient, a difference of charge, across the plasma membrane. The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed, and at the same time, cells have higher concentrations of potassium (K+) and lower concentrations of sodium (Na+) than does the extracellular fluid. So in a living cell, the concentration gradient of Na+ tends to drive it into the cell, and the electrical gradient of Na+ (a positive ion) also tends to drive it inward to the negatively charged interior. The situation is more complex, however, for other elements such as potassium. The electrical gradient of K+, a positive ion, also tends to drive it into the cell, but the concentration gradient of K+ tends to drive K+ out of the cell (Figure 5.16). The combined gradient of concentration and electrical charge that affects an ion is called its electrochemical gradient. 214 Chapter 5 \| Structure and Function of Plasma Membranes Figure 5.16 Electrochemical gradients arise from the combined effects of concentration gradients and electrical gradients. Structures labeled A represent proteins. (credit: “Synaptitude”/Wikimedia Commons) If the pH outside the cell decreases, would you expect the amount of amino acids transported into the cell to increase or decrease? a. Transport of amino acids into the cell increases b. Transport of amino acids into the cell stops. c. Transport of amino acids into the cell is not affected by pH. d. Transport of amino acid into the cell decreases
. Moving Against a Gradient To move substances against a concentration or electrochemical gradient, the cell must use energy. This energy is harvested from ATP generated through the cell’s metabolism. Active transport mechanisms, collectively called pumps, work against electrochemical gradients. Small substances constantly pass through plasma membranes. Active transport maintains concentrations of ions and other substances needed by living cells in the face of these passive movements. Much of a cell’s supply of metabolic energy may be spent maintaining these processes. (Most of a red blood cell’s metabolic energy is used to maintain the imbalance between exterior and interior sodium and potassium levels required by the cell.) Because active transport mechanisms depend on a cell’s metabolism for energy, they are sensitive to many metabolic poisons that interfere with the supply of ATP. Two mechanisms exist for the transport of small-molecular weight material and small molecules. Primary active transport moves ions across a membrane and creates a difference in charge across that membrane, which is directly dependent on ATP. Secondary active transport describes the movement of material that is due to the electrochemical gradient established by primary active transport that does not directly require ATP. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 215 Carrier Proteins for Active Transport An important membrane adaption for active transport is the presence of specific carrier proteins or pumps to facilitate movement: there are three types of these proteins or transporters (Figure 5.17). A uniporter carries one specific ion or molecule. A symporter carries two different ions or molecules, both in the same direction. An antiporter also carries two different ions or molecules, but in different directions. All of these transporters can also transport small, uncharged organic molecules like glucose. These three types of carrier proteins are also found in facilitated diffusion, but they do not require ATP to work in that process. Some examples of pumps for active transport are Na+-K+ ATPase, which carries sodium and potassium ions, and H+-K+ ATPase, which carries hydrogen and potassium ions. Both of these are antiporter carrier proteins. Two other carrier proteins are Ca2+ ATPase and H+ ATPase, which carry only calcium and only hydrogen ions, respectively. Both are pumps. Figure 5.17 A uniporter carries one molecule or ion. A symporter carries two different molecules or ions, both in the same direction
. An antiporter also carries two different molecules or ions, but in different directions. (credit: modification of work by “Lupask”/Wikimedia Commons) 216 Chapter 5 \| Structure and Function of Plasma Membranes The primary active transport that functions with the active transport of sodium and potassium allows secondary active transport to occur. The second transport method is still considered active because it depends on the use of energy as does primary transport (illustrative example). Figure 5.18 Primary active transport moves ions across a membrane, creating an electrochemical gradient (electrogenic transport). (credit: modification of work by Mariana Ruiz Villareal) One of the most important pumps in animal cells is the sodium-potassium pump (Na+-K+ ATPase), which maintains the electrochemical gradient (and the correct concentrations of Na+ and K+) in living cells. The sodium-potassium pump moves K+ into the cell while moving Na+ out at the same time, at a ratio of three Na+ for every two K+ ions moved in. The Na+-K+ ATPase exists in two forms, depending on its orientation to the interior or exterior of the cell and its affinity for either sodium or potassium ions. The process consists of the following six steps: 1. With the enzyme oriented towards the interior of the cell, the carrier has a high affinity for sodium ions. Three ions bind to the protein. 2. The protein carrier hydrolyzes ATP and a low-energy phosphate group attaches to it. 3. As a result, the carrier changes shape and re-orients itself towards the exterior of the membrane. The protein’s affinity for sodium decreases and the three sodium ions leave the carrier. 4. The shape change increases the carrier’s affinity for potassium ions, and two such ions attach to the protein. Subsequently, the low-energy phosphate group detaches from the carrier. 5. With the phosphate group removed and potassium ions attached, the carrier protein repositions itself towards the interior of the cell. 6. The carrier protein, in its new configuration, has a decreased affinity for potassium, and the two ions are released into the cytoplasm. The protein now has a higher affinity for sodium ions, and the process starts again. Several things have happened as a result of this process. At this point, there are more sodium ions outside of the cell than inside and more potassium ions inside than out. For every three ions of sodium that move out,
two ions of potassium move in. This results in the interior being slightly more negative relative to the exterior. This difference in charge is important to creating the conditions necessary for the secondary process. Therefore, the sodium-potassium pump is an electrogenic pump (a pump that creates a charge imbalance) contributing to the membrane potential. What will happen to the opening of the sodium-potassium pump if no ATP is present in a cell? a. b. c. It will remain facing the extracellular space, with sodium ions bound. It will remain facing the extracellular space, with potassium ions bound. It will remain facing the cytoplasm, but no sodium ions would bind. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 217 d. It will remain facing the cytoplasm, with sodium ions bound. Visit the site (http://openstaxcollege.org/l/Na_K_ATPase) to see a simulation of active transport in a sodium-potassium ATPase. Sodium and potassium are necessary electrolytes. As a result, the human body uses a great deal of energy keeping these electrolytes in balance. Explain why the body needs to use energy for this process. a. ATP is required to move sodium ions against their concentration gradient outside the cell. b. ATP is required to allow entry of potassium ions inside the cell. c. ATP is required to allow entry of sodium ions inside the cell. d. ATP is required to release potassium ions outside the cell. Activity Create a representation/diagram (or use the model you constructed of the plasma cell membrane) to explain how the sodium-potassium pump contributes to the net negative change of the interior of an animal nerve cell. Think About It If the pH outside the cell decreases, would you expect the amount of amino acids and glucose transported into the cell to increase or decrease? Justify your reasoning. Secondary Active Transport (Co-transport) Secondary active transport brings sodium ions, and possibly other compounds, into the cell. As sodium ion concentrations build outside of the plasma membrane because of the action of the primary active transport process, an electrochemical gradient is created. If a channel protein exists and is open, the sodium ions will be pulled through the membrane. This movement is used to transport other substances that can attach themselves to the transport protein through the membrane (Figure 5.19
). Many amino acids, as well as glucose, enter a cell this way. This secondary process is also used to store high-energy hydrogen ions in the mitochondria of plant and animal cells for the production of ATP. The potential energy that accumulates in the stored hydrogen ions is translated into kinetic energy as the ions surge through the channel protein ATP synthase, and that energy is used to convert ADP into ATP. 218 Chapter 5 \| Structure and Function of Plasma Membranes Figure 5.19 An electrochemical gradient, created by primary active transport, can move other substances against their concentration gradients, a process called co-transport or secondary active transport. (credit: modification of work by Mariana Ruiz Villareal) Injection of a potassium solution into a person’s blood is lethal. Potassium is used in capital punishment and euthanasia. Why do you think a potassium solution injection is lethal? a. Excess potassium disrupts the membrane components b. Excess potassium increases action potential generation, leading to uncoordinated organ activity. c. Potassium dissipates the electrochemical gradient in cardiac muscle cells, preventing them from contracting. d. Potassium creates a new concentration gradient across the cell membrane, preventing sodium from leaving the cell. 5.4 \| Bulk Transport By the end of this section, you will be able to: • What are the differences among the different types of endocytosis: (phagocytosis, pinocytosis, and receptor- mediated endocytosis) and exocytosis? Connection for AP® Courses Diffusion, osmosis, and active transport are used to transport fairly small molecules across plasma cell membranes. However, sometimes large particles, such as macromolecules, parts of cells, or even unicellular microorganisms, can be engulfed by other cells in a process called phagocytosis or “cell eating.” In this form of endocytosis, the cell membrane surrounds the particle, pinches off, and brings the particle into the cell. For example, when bacteria invade the human body, a type of white blood cell called a neutrophil will remove the invaders by this process. Similarly, in pinocytosis or “cell drinking,” the cell takes in droplets of liquid. In receptor-mediated endocytosis, uptake of substances by the cell is targeted to a single type of substance that binds to a specific receptor protein on the external surface of the cell
membrane (e.g., hormones and their target cells) before under going endocytosis. Some human diseases, such as familial hypercholesterolemia, are caused by the failure of receptor-mediated endocytosis. Exocytosis is the process of exporting This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 219 material out of the cell; vesicles containing substances fuse with the plasma membrane and the contents are released to the exterior of the cell. The secretion of neurotransmitters at synapses between neurons is an example of exocytosis. Information presented and the examples highlighted in the section support concepts and learning objectives outlined in Big Idea 2 of the AP® Biology Curriculum Framework. The learning objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A learning objective merges required content with one or more of the seven science practices. Big Idea 2 Enduring Understanding 2.B Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and dynamic homeostasis require that cells create and maintain internal environments that are different from their external environments. Essential Knowledge 2.B.2 Growth and dynamic homeostasis are maintained by the constant movement of molecules across membranes. Science Practice Learning Objective Big Idea 2 Enduring Understanding 2.D 1.4 The student can use representations and models to analyze situations or solve problems qualitatively and quantitatively. 2.12 The student is able to use representations and models to analyze situations or solve problems qualitatively and quantitatively to investigate whether dynamic homeostasis is maintained by the active movement of molecules across membranes. Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth and dynamic homeostasis of a biological system are influenced by changes in the system’s environment. Essential Knowledge 2.D.4 Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis. Science Practice Science Practice Learning Objective 1.1 The student can create representations and models of natural or man-made phenomena and systems in the domain. 1.2 The student can describe representations and models of natural or man-made phenomena and systems in the domain. 2.30 The student can create
representations or models to describe nonspecific immune defenses in plants and animals. In addition to moving small ions and molecules through the membrane, cells also need to remove and take in larger molecules and particles (see Table 5.2 for examples). Some cells are even capable of engulfing entire unicellular microorganisms. You might have correctly hypothesized that the uptake and release of large particles by the cell requires energy. A large particle, however, cannot pass through the membrane, even with energy supplied by the cell. Endocytosis Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. There are different variations of endocytosis, but all share a common characteristic: The plasma membrane of the cell invaginates, forming a pocket around the target particle. The pocket pinches off, resulting in the particle being contained in a newly created intracellular vesicle formed from the plasma membrane. Phagocytosis Phagocytosis (the condition of “cell eating”) is the process by which large particles, such as cells or relatively large particles, are taken in by a cell. For example, when microorganisms invade the human body, a type of white blood cell called a neutrophil will remove the invaders through this process, surrounding and engulfing the microorganism, which is then destroyed by the neutrophil (Figure 5.20). 220 Chapter 5 \| Structure and Function of Plasma Membranes Figure 5.20 In phagocytosis, the cell membrane surrounds the particle and engulfs it. (credit: Mariana Ruiz Villareal) In preparation for phagocytosis, a portion of the inward-facing surface of the plasma membrane becomes coated with a protein called clathrin, which stabilizes this section of the membrane. The coated portion of the membrane then extends from the body of the cell and surrounds the particle, eventually enclosing it. Once the vesicle containing the particle is enclosed within the cell, the clathrin disengages from the membrane and the vesicle merges with a lysosome for the breakdown of the material in the newly formed compartment (endosome). When accessible nutrients from the degradation of the vesicular contents have been extracted, the newly formed endosome merges with the plasma membrane and releases its contents into the extracellular fluid. The endosomal membrane again becomes part of the plasma membrane
. Activity Create a representation/diagram to describe how a neutrophil, a type of human white blood cell, attacks and destroys an invading bacterium. What cellular organelles are involved in this process? Pinocytosis A variation of endocytosis is called pinocytosis. This literally means “cell drinking” and was named at a time when the assumption was that the cell was purposefully taking in extracellular fluid. In reality, this is a process that takes in molecules, including water, which the cell needs from the extracellular fluid. Pinocytosis results in a much smaller vesicle than does phagocytosis, and the vesicle does not need to merge with a lysosome (Figure 5.21). This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 221 Figure 5.21 In pinocytosis, the cell membrane invaginates, surrounds a small volume of fluid, and pinches off. (credit: Mariana Ruiz Villareal) A variation of pinocytosis is called potocytosis. This process uses a coating protein, called caveolin, on the cytoplasmic side of the plasma membrane, which performs a similar function to clathrin. The cavities in the plasma membrane that form the vacuoles have membrane receptors and lipid rafts in addition to caveolin. The vacuoles or vesicles formed in caveolae (singular caveola) are smaller than those in pinocytosis. Potocytosis is used to bring small molecules into the cell and to transport these molecules through the cell for their release on the other side of the cell, a process called transcytosis. Receptor-mediated Endocytosis A targeted variation of endocytosis employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances (Figure 5.22). 222 Chapter 5 \| Structure and Function of Plasma Membranes Figure 5.22 In receptor-mediated endocytosis, uptake of substances by the cell is targeted to a single type of substance that binds to the receptor on the external surface of the cell membrane. (credit: modification of work by Mariana Ruiz Villareal) In receptor-mediated endocytosis, as in phagocytosis, clathrin is attached to
the cytoplasmic side of the plasma membrane. If uptake of a compound is dependent on receptor-mediated endocytosis and the process is ineffective, the material will not be removed from the tissue fluids or blood. Instead, it will stay in those fluids and increase in concentration. Some human diseases are caused by the failure of receptor-mediated endocytosis. For example, the form of cholesterol termed low-density lipoprotein or LDL (also referred to as “bad” cholesterol) is removed from the blood by receptor-mediated endocytosis. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood, because their cells cannot clear LDL particles from their blood. Although receptor-mediated endocytosis is designed to bring specific substances that are normally found in the extracellular fluid into the cell, other substances may gain entry into the cell at the same site. Flu viruses, diphtheria, and cholera toxin all have sites that cross-react with normal receptor-binding sites and gain entry into cells. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 223 See receptor-mediated endocytosis in action, and click on different parts (http://openstaxcollege.org/l/endocytosis) for a focused animation. Salmonella is one of the most common food borne illnesses. When salmonella bacteria are engulfed by a white blood cell during phagocytosis, it secretes a protein that prevents the fusion of the encased bacteria with the lysosome of the cell. What effect would this have? a. The bacteria will be destroyed and will not cause any illness. b. The bacteria will survive and will definitely result in illness. c. The bacteria will be destroyed, but will still cause illness. d. The bacteria will survive and possibly will cause illness. Exocytosis The reverse process of moving material into a cell is the process of exocytosis. Exocytosis is the opposite of the processes discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the interior of the plasma membrane. This fusion opens the membranous envelope
on the exterior of the cell, and the waste material is expelled into the extracellular space (Figure 5.23). Other examples of cells releasing molecules via exocytosis include the secretion of proteins of the extracellular matrix and secretion of neurotransmitters into the synaptic cleft by synaptic vesicles. Figure 5.23 In exocytosis, vesicles containing substances fuse with the plasma membrane. The contents are then released to the exterior of the cell. (credit: modification of work by Mariana Ruiz Villareal) 224 Chapter 5 \| Structure and Function of Plasma Membranes Methods of Transport, Energy Requirements, and Types of Material Transported Transport Method Diffusion Osmosis Active/ Passive Passive Passive Material Transported Small-molecular weight material Water Facilitated transport/diffusion Passive Sodium, potassium, calcium, glucose Primary active transport Secondary active transport Phagocytosis Active Active Active Sodium, potassium, calcium Amino acids, lactose Large macromolecules, whole cells, or cellular structures Pinocytosis and potocytosis Active Small molecules (liquids/water) Receptor-mediated endocytosis Table 5.2 Active Large quantities of macromolecules This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 225 KEY TERMS active transport method of transporting material that requires energy amphiphilic molecule possessing a polar or charged area and a nonpolar or uncharged area capable of interacting with both hydrophilic and hydrophobic environments antiporter transporter that carries two ions or small molecules in different directions aquaporin channel protein that allows water through the membrane at a very high rate carrier protein membrane protein that moves a substance across the plasma membrane by changing its own shape caveolin protein that coats the cytoplasmic side of the plasma membrane and participates in the process of liquid uptake by potocytosis channel protein membrane protein that allows a substance to pass through its hollow core across the plasma membrane clathrin protein that coats the inward-facing surface of the plasma membrane and assists in the formation of specialized structures, like coated pits, for phagocytosis concentration gradient area of high concentration adjacent to an area of low concentration diffusion passive process of transport of low-molecular weight material according to its concentration gradient electrochemical gradient gradient produced by the combined forces of an electrical gradient and a chemical gradient electrogen
ic pump pump that creates a charge imbalance endocytosis type of active transport that moves substances, including fluids and particles, into a cell exocytosis process of passing bulk material out of a cell facilitated transport process by which material moves down a concentration gradient (from high to low concentration) using integral membrane proteins fluid mosaic model describes the structure of the plasma membrane as a mosaic of components including phospholipids, cholesterol, proteins, glycoproteins, and glycolipids (sugar chains attached to proteins or lipids, respectively), resulting in a fluid character (fluidity) glycolipid combination of carbohydrates and lipids glycoprotein combination of carbohydrates and proteins hydrophilic molecule with the ability to bond with water; “water-loving” hydrophobic molecule that does not have the ability to bond with water; “water-hating” hypertonic situation in which extracellular fluid has a higher osmolarity than the fluid inside the cell, resulting in water moving out of the cell hypotonic situation in which extracellular fluid has a lower osmolarity than the fluid inside the cell, resulting in water moving into the cell integral protein protein integrated into the membrane structure that interacts extensively with the hydrocarbon chains of membrane lipids and often spans the membrane; these proteins can be removed only by the disruption of the membrane by detergents isotonic situation in which the extracellular fluid has the same osmolarity as the fluid inside the cell, resulting in no net movement of water into or out of the cell osmolarity total amount of substances dissolved in a specific amount of solution 226 Chapter 5 \| Structure and Function of Plasma Membranes osmosis transport of water through a semipermeable membrane according to the concentration gradient of water across the membrane that results from the presence of solute that cannot pass through the membrane passive transport method of transporting material through a membrane that does not require energy peripheral protein protein found at the surface of a plasma membrane either on its exterior or interior side pinocytosis a variation of endocytosis that imports macromolecules that the cell needs from the extracellular fluid plasmolysis detaching of the cell membrane from the cell wall and constriction of the cell membrane when a plant cell is in a hypertonic solution potocytosis variation of pinocytosis that uses a different coating protein (caveolin) on the cytoplasmic side of the plasma membrane primary active
transport active transport that moves ions or small molecules across a membrane and may create a difference in charge across that membrane pump active transport mechanism that works against electrochemical gradients receptor-mediated endocytosis variation of endocytosis that involves the use of specific binding proteins in the plasma membrane for specific molecules or particles, and clathrin-coated pits that become clathrin-coated vesicles secondary active transport movement of material that is due to the electrochemical gradient established by primary active transport selectively permeable characteristic of a membrane that allows some substances through but not others solute substance dissolved in a liquid to form a solution symporter transporter that carries two different ions or small molecules, both in the same direction tonicity amount of solute in a solution transport protein membrane protein that facilitates passage of a substance across a membrane by binding it transporter specific carrier proteins or pumps that facilitate movement uniporter transporter that carries one specific ion or molecule CHAPTER SUMMARY 5.1 Components and Structure The modern understanding of the plasma membrane is referred to as the fluid mosaic model. The plasma membrane is composed of a bilayer of phospholipids, with their hydrophobic, fatty acid tails in contact with each other. The landscape of the membrane is studded with proteins, some of which span the membrane. Some of these proteins serve to transport materials into or out of the cell. Carbohydrates are attached to some of the proteins and lipids on the outward-facing surface of the membrane, forming complexes that function to identify the cell to other cells. The fluid nature of the membrane is due to temperature, the configuration of the fatty acid tails (some kinked by double bonds), the presence of cholesterol embedded in the membrane, and the mosaic nature of the proteins and protein-carbohydrate combinations, which are not firmly fixed in place. Plasma membranes enclose and define the borders of cells, but rather than being a static bag, they are dynamic and constantly in flux. 5.2 Passive Transport The passive forms of transport, diffusion and osmosis, move materials of small molecular weight across membranes. Substances diffuse from areas of high concentration to areas of lower concentration, and this process continues until the substance is evenly distributed in a system. In solutions containing more than one substance, each type of molecule diffuses according to its own concentration gradient, independent of the diffusion of other substances. Many factors can affect the rate of diffusion, including concentration gradient, size of the particles that are diffusing, temperature of the system, and
so on. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 227 In living systems, diffusion of substances into and out of cells is mediated by the plasma membrane. Some materials diffuse readily through the membrane, but others are hindered, and their passage is made possible by specialized proteins, such as channels and transporters. The chemistry of living things occurs in aqueous solutions, and balancing the concentrations of those solutions is an ongoing problem. In living systems, diffusion of some substances would be slow or difficult without membrane proteins that facilitate transport. 5.3 Active Transport The combined gradient that affects an ion includes its concentration gradient and its electrical gradient. A positive ion, for example, might tend to diffuse into a new area, down its concentration gradient, but if it is diffusing into an area of net positive charge, its diffusion will be hampered by its electrical gradient. When dealing with ions in aqueous solutions, a combination of the electrochemical and concentration gradients, rather than just the concentration gradient alone, must be considered. Living cells need certain substances that exist inside the cell in concentrations greater than they exist in the extracellular space. Moving substances up their electrochemical gradients requires energy from the cell. Active transport uses energy stored in ATP to fuel this transport. Active transport of small molecular-sized materials uses integral proteins in the cell membrane to move the materials: These proteins are analogous to pumps. Some pumps, which carry out primary active transport, couple directly with ATP to drive their action. In co-transport (or secondary active transport), energy from primary transport can be used to move another substance into the cell and up its concentration gradient. 5.4 Bulk Transport Active transport methods require the direct use of ATP to fuel the transport. Large particles, such as macromolecules, parts of cells, or whole cells, can be engulfed by other cells in a process called phagocytosis. In phagocytosis, a portion of the membrane invaginates and flows around the particle, eventually pinching off and leaving the particle entirely enclosed by an envelope of plasma membrane. Vesicle contents are broken down by the cell, with the particles either used as food or dispatched. Pinocytosis is a similar process on a smaller scale. The plasma membrane invaginates and pinches off, producing a small envelope of fluid from outside the cell. Pinocy
tosis imports substances that the cell needs from the extracellular fluid. The cell expels waste in a similar but reverse manner: it pushes a membranous vacuole to the plasma membrane, allowing the vacuole to fuse with the membrane and incorporate itself into the membrane structure, releasing its contents to the exterior. REVIEW QUESTIONS 1. Which plasma membrane component can be either found on its surface or embedded in the membrane structure? a. carbohydrates b. cholesterol c. glycolipid d. protein 2. In addition to a plasma membrane, eukaryotic cell organelles, such as mitochondria, also have membranes. In which way would these membranes differ? a. cholesterol b. c. its head saturated fatty acid tail d. unsaturated fatty acid tail 4. How would an organism maintain membrane fluidity in an environment where temperatures fluctuated from very high to very low? a. Greater proportion of unsaturated phospholipids in membranes. b. Greater proportion of saturated phospholipids in a. The proportion of phosphate within the membranes. phospholipids will vary. c. Greater proportion of carbohydrates in b. Only certain membranes contain phospholipids. membranes. c. Only certain membranes are selectively d. Greater proportion of proteins in membranes. permeable. d. The proportions of proteins, lipids, and carbohydrates will vary. 3. Which characteristic of a phospholipid increases the fluidity of the membrane? 5. According to the fluid mosaic model of the plasma cell membrane, what is the primary function of carbohydrates attached to the exterior of cell membranes? 228 Chapter 5 \| Structure and Function of Plasma Membranes a. Carbohydrates are in contact with the aqueous a. They will have higher concentrations of body fluid both inside and outside the cell. solutes. b. Carbohydrates are present only on the interior b. Without compensating mechanisms, their bodies surface of a membrane. tend to take in too much water. c. Carbohydrates are present only on the exterior c. They have no way of controlling their tonicity. surface of a membrane. d. Their bodies tend to lose too much water to their d. Carbohydates span only the interior of a environment. membrane. 6. What do double bonds in phospholipid fatty acid tails contribute to? a. b. c. the fluidity of membranes the hydrophobic nature of membranes the hydrophilic nature of membranes 11. Which of the following questions can be
asked about organisms that live in fresh water? a. Will their bodies take in too much water? b. Can they control their tonicity? c. Can they survive in salt water? d. Will their bodies lose too much water to their d. preventing high temperatures from increasing environment? fluidity of membranes 7. Identify the principal force driving movement in diffusion. a. concentration gradient b. membrane surface area c. particle size d. temperature 8. Which of the following is an example of passive transport across a membrane? a. b. c. d. the movement of H+ into a thylakoid disc during photosynthesis the uptake of glucose in the intestine the uptake of mineral ions into root hair cells of plants the movement of water from a nephron into the collecting duct of the kidney 9. Water moves via osmosis across plasma cell membranes in which direction? a. b. c. from an area with a high concentration of other solutes to a lower one from an area with a high concentration of water to one of lower concentration from an area with a low concentration of water to one of higher concentration. d. throughout the cytoplasm 10. What problem is faced by organisms that live in fresh water? 12. Which of the following explains why active movement of molecules across membranes must function continuously? 13. Why must active transport of molecules across plasma membranes function continuously? a. Diffusion cannot occur in certain cells. b. Diffusion is constantly moving solutes in opposite directions. c. Facilitated diffusion works in the same direction as active transport. d. Not all membranes are amphiphilic. 14. How does the sodium-potassium pump make the interior of the cell negatively charged? a. by expelling anions b. by pulling in anions c. by expelling more cations than it takes in d. By taking in and expelling an equal number of cations. 15. What is the difference between primary and secondary active transport? a. Primary active transport is indirectly dependent on ATP, while secondary active transport is directly dependent on ATP. b. Primary active transport is directly dependent on ATP, while secondary active transport is indirectly dependent on ATP. c. Primary active transport does not require ATP, while secondary active transport is indirectly dependent on ATP. d. Primary active transport is indirectly dependent on ATP, while secondary active transport does not require ATP 16. What happens to the membrane of a vesicle after exocytosis? This OpenStax book is available for
free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 229 a. b. c. d. It transports only small amounts of fluid. It does not involve the pinching off of membrane. It brings in only a specifically targeted substance. It brings substances into the cell, while phagocytosis removes substances. a. Phospholipids: form the bilayer; Carbohydrates: help in adhesion; Cholesterol: provide flexibility; Integral proteins: form transporters; Peripheral proteins: part of the cell’s recognition sites. b. Phospholipids: form the bilayer; Carbohydrates: help in adhesion; Cholesterol: form transporters; Integral proteins: provide flexibility; Peripheral proteins: part of the cell’s recognition sites. c. Phospholipids: form the bilayer; Carbohydrates: part of the cell’s recognition sites; Cholesterol: provide flexibility to the membrane; Integral proteins: form transporters; Intermediate filaments: help in adhesion. d. Phospholipids: form the bilayer; Carbohydrates: function as adhesion; Cholesterol: provide flexibility to the membrane, Integral proteins: form transporters; Intermediate filaments: part of the cell’s recognition sites. 21. Discuss why the following affect the rate of diffusion: molecular size, temperature, solution density, and the distance that must be traveled. a. b. c. It leaves the cell. It is disassembled by the cell. It fuses with and becomes part of the plasma membrane. d. It is used again in another exocytosis event. 17. In what important way does receptor-mediated endocytosis differ from phagocytosis? CRITICAL THINKING QUESTIONS 18. Why do phospholipids tend to spontaneously orient themselves into something resembling a membrane? a. Phospholipids are amphipathic molecules. The polar head faces towards water and the nonpolar fatty acid tails face towards other fatty acid tails. b. Phospholipids are lipophilic molecules. The polar head faces towards water and the nonpolar fatty acid tails face towards other fatty acid tails c. Phospholipids are amphipathic molecules. The nonpolar head faces towards other fatty acid tails and
the polar fatty acid tails face towards water. d. Phospholipids are hydrophilic molecules. The polar head faces towards water and the nonpolar fatty acid tails face towards other fatty acid tails. 19. Why is it advantageous for the plasma membrane to be fluid in nature? a. Fluidity allows greater flexibility to the cell and motion of membrane components required for transport. b. Fluidity helps only in transport of some materials, and does not contribute to the flexibility. c. Fluidity helps in maintaining the pH of intracellular fluid, and helps in maintaining the physiological pH of the cell. d. Fluidity helps in providing mechanical strength to the plasma membrane. 20. List four components of a plasma membrane and explain their function. 230 Chapter 5 \| Structure and Function of Plasma Membranes a. The sodium-potassium pump forces out three (positive) Na+ ions for every two (positive) K+ ions it pumps in, thus the cell loses a net positive charge of one at every cycle of the pump. b. The sodium-potassium pump expels three ions K+ for every two Na+ inside the cells, creating a net positive charge outside the cell and a net negative charge inside the cell. c. The sodium-potassium pump helps the development of negative charge inside the cell by making the membrane more permeable to negatively charged proteins. d. The sodium-potassium pump helps in the development of negative charge inside the cell by making the membrane impermeable to positively charged ions. 25. Potassium is a necessary nutrient in order to maintain the function of our cells. What would occur to a person that is deficient in potassium? a. The excess sodium disrupts the membrane components. b. The excess sodium increases action potential generation. c. The cell would not be able to get rid of extra sodium. d. The cell would not be able to bring sodium into the cell. 26. Choose the statement that describes processes of receptor-mediated endocytosis, exocytosis, and the changes in the membrane organization. a. Larger molecules move faster than lighter molecules. Temperature affects the molecular movement. Density is directly proportional to the molecular movement. Greater distance slows the diffusion. b. Larger molecules move slower than lighter molecules. Increasing or decreasing temperature increases or decreases the energy in the medium, affecting molecular movement. Density is inversely proportional to molecular movement. Greater distance slows the diffusion. c. Larger molecules move slower than lighter molecules.
Temperature does not affect the rate of diffusion. Density is inversely proportional to molecular movement. Greater distance speeds up the diffusion. d. Larger molecules move slower than lighter molecules. Increasing or decreasing temperature increases or decreases the energy in the medium, affecting molecular movement. Density is inversely proportional to the molecular movement. Greater distance speeds up the diffusion. 22. Both of the regular intravenous solutions administered in medicine, normal saline and lactated Ringer’s solution, are isotonic. Why is this important? a. b. c. d. Isotonic solutions maintain equilibrium and avoid the exchange of materials to or from the blood. Isotonic solutions disrupt equilibrium and allow better exchange of materials in the blood. Isotonic solutions increase the pH of blood and allow better absorption of saline in blood. Isotonic solutions decrease the pH of the blood and avoid the exchange of materials to or from the blood. 23. If a doctor injected a patient with what was labeled as an isotonic saline solution, but then the patient died, and an autopsy revealed that several of the patient's red blood cells had burst, would it be true that the injected solution was really isotonic? Why or why not? a. False, the solution was hypertonic. b. False, the solution was osmotic. c. False, the solution was hypotonic. d. True, the solution was isotonic. 24. How does the sodium-potassium pump contribute to the net negative charge of the interior of the cell? This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 231 a. Endocytosis involves the opsonization of a receptor and its ligand in clathrin-coated vesicles, along with the inward budding of the plasma membrane. In exocytosis, waste material is enveloped in a membrane that fuses with the interior of the plasma membrane via attachment proteins. b. c. In endocytosis, waste material is enveloped in a membrane that fuses with the interior of the plasma membrane via attachment proteins. Exocytosis involves the opsonization of the receptor and its ligand in a clathrin-coated vesicles. In endocytosis, waste material is enveloped in a membrane that fuses with the interior of the plasma membrane via attachment proteins. Exocytosis involves
the opsonization of the receptor and its ligand in caveolae-coated vesicles. d. Endocytosis involves the opsonization of the receptor and its ligand in clathrin-coated vesicles. In exocytosis, waste material is enveloped in a membrane that fuses with the exterior of the plasma membrane via attachment proteins. TEST PREP FOR AP® COURSES 28. One type of mutation in the CFTR protein prevents the transport of chloride ions through the channel. Which of the following is most likely to be observed in the lungs of patients with this mutation? a. dehydrated epithelial cells b. dehydrated mucus c. mucus with excess water d. mucus with high electrolyte concentration 29. Arsenic poisoning disrupts ATP production by inhibiting several of the enzymes in the oxidative phosphorylation pathway. Some of the symptoms of arsenic poisoning are similar to cystic fibrosis (difficulty breathing and frequent lung infections). Explain what impact arsenic poisoning may have on components of the plasma membrane and transport that result in CF like symptoms. 27. Describe the process of potocytosis and explain how it differs from pinocytosis. a. Potocytosis is a form of receptor-mediated endocytosis where molecules are transported via caveolae-coated vesicles. Pinocytosis is a form of exocytosis used for excreting excess water. b. Potocytosis is a form of exocytosis where molecules are transported via clathrin-coated vesicles. Pinocytosis is a form of receptormediated endocytosis used for excreting excess water. c. Potocytosis is a form of receptor-mediated endocytosis where molecules are transported via caveolae-coated vesicles. Pinocytosis is a mode of endocytosis used for absorption of extracellular water. d. Potocytosis is a form of receptor-mediated endocytosis used for absorption of water. Pinocytosis is a mode of endocytosis used for excretion of extracellular water. a. Arsenic poisoning disrupts ATP production, leading to decreased transport of Cl− ions by epithelial cells. This leads to decreased electrolyte concentration in the mucus and retention of water into the cells. The mucus becomes dehydrated, as in CF. b. Arsen
ic poisoning disrupts the Na+ / Cl− pump, leading to decreased transport of Cl− ions outside the epithelial cells. This increases the electrolyte concentration in the mucus and movement of water out of the cells. The mucus becomes hydrated as in CF. c. Arsenic poisoning affects the oxidative phosphorylation pathway, leading to decreased transport of Na+ ions outside the epithelial cells. This leads to increased electrolyte concentration in the mucus and movement of water into the cells. The mucus becomes dehydrated as in CF. d. Arsenic poisoning disrupts the binding sites for Cl− ions, leading to decreased transport of Cl− ions outside the epithelial cells. This leads to decreased electrolyte concentration in the mucus and movement of water outside the cells. The mucus becomes hydrated as in CF. 30. In individuals with normally functioning CFTR 232 Chapter 5 \| Structure and Function of Plasma Membranes protein, which substances are transported via active transport? a. Cl− b. mucus c. Na+ d. water 31. Paramecia are unicellular protists that have contractile vacuoles to remove excess intracellular water. In an experimental investigation, Paramecia were placed in salt solutions of increasing osmolarity. The rate at which a Paramecium's contractile vacuole contracted to pump out excess water was determined and plotted against osmolarity of the solutions, as shown in the graph. Which of the following is the correct explanation for the data? a. At higher osmolarity, lower rates of contraction are required because more salt diffuses into the Paramecium. b. In an isosmotic salt solution, there is no diffusion of water into or out of the Paramecium, so the contraction rate is zero. c. The contraction rate increases as the osmolarity decreases because the amount of water entering the Paramecium by osmosis increases. d. The contractile vacuole is less efficient in solutions of high osmolarity because of the reduced amount of ATP produced from cellular respiration. 33. What is most likely to happen if Paramecia are moved from a hypertonic solution to solutions of decreasing osmolarity? a. The rate of contraction would increase with decreasing osmolarity because more water diffuses into the Paramecium. b. The rate of contraction would decrease with decreasing osmolarity because more water diffuses into the Parame
cium. c. The rate of contraction would increase with decreasing osmolarity because more salt diffuses into the Paramecium. d. The rate of contraction would decrease with decreasing osmolarity because more salt diffuses into the Paramecium. The sodium-potassium (Na+ / K+ ) pump functions like an anti-porter transporting Na+ and K+ across membranes using ATP. This protein spans the membrane with intracellular and extracellular domains. It has a binding site for Na+, K+, and ATP. An experiment was conducted to determine the locations of these binding sites. Artificial cells were created and incubated in buffers containing ATP, ouabain (or oubain), Na+, and K+ in varying combinations inside and outside of the cell as indicated in the chart. The transport of Na+ and K+ was measured to determine activity of the Na+ / K+ pump. Which of the following conclusions is supported by the data? a. Ouabain can disrupt ATP binding to the Na+ / K+ pump. b. ATP is required for transport of Na+ and not for transport of K+. c. The ATP binding site of the Na+ / K+ pump is located on the intracellular domain of the pump. d. The ATP binding site of the Na+ / K+ pump is located on the extracellular domain of the pump. 32. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 233 34. Describe the Na+ / K+ pump, labeling the binding sites for Na+, K+, and ATP. Explain how the data indicates the location of the binding sites for Na+ and K+ on the pump. Based on the data, choose the correct statement describing the location of the binding sites for Na+ and K+ on the pump. An experiment was set up to determine the movement of molecules through a dialysis-tubing bag into water. A dialysis-tubing bag containing 5% lactose and 5% fructose was placed in a beaker of distilled water, as illustrated. After four hours, fructose is detected in the distilled water outside of the dialysis-tubing bag, but lactose is not. What conclusions can be made about the movement of molecules in this experiment? a. The binding of Na+ occurs on the outer surface of the cell,
as its transportation remains unaffected by the presence of ouabain. The binding of K+ occurs on the inner surface of the cell, as its transportation is blocked when ouabain is present inside the cell b. The binding of K+ occurs on the outer surface of the cell, as its transportation is blocked when ouabain is present outside the cell. The binding of Na+ occurs on the inner surface of the cell as its transportation remains unaffected by the presence of ouabain. c. The binding of K+ occurs on the outer surface of the cell and the binding of Na+ occurs on the inner surface of the cell, as they are not transported when ATP is absent. d. The binding of Na+ occurs on the outer surface of the cell and the binding of K+ occurs on the inner surface of the cell, as they are not transported when ATP is absent. 35. a. Fructose, being a monosaccharide, diffused through the dialysis bag into the distilled water. However, lactose, being a disaccharide, could not diffuse through the dialysis bag. b. Fructose was homogenized by lactose, allowing the fructose to diffuse through the dialysis bag and into the distilled water. Lactose is not homogenized, so it could not pass through the dialysis bag. c. Fructose and lactose are oppositely charged and separated out due to the force of repulsion. d. Fructose diffused because of the pore specificity of the semipermeable membrane, not because of its concentration gradient. 36. Based on the information provided, which cell types are most likely to contain clathrin? a. monocytes and mast cells b. neutrophils, monocytes, and mast cells c. neutrophils and mast cells d. neutrophils and monocytes 37. Which of the following statements appropriately describe the role of opsonin and clathrin proteins in neutrophils based on your understanding of phagocytosis? 234 Chapter 5 \| Structure and Function of Plasma Membranes 38. Based on the information provided, which cell types produce endosomes? a. monocytes and mast cells b. neutrophils, monocytes, and mast cells c. neutrophils and mast cells d. neutrophils and monocytes a. A clathrin coating enhances phagocytosis, whereas opsonin reverses the process of phagocytosis.
b. Opsonins are proteins that enhance phagocytosis, whereas clathrin opposes phagocytosis. c. Opsonin stabilizes the inward facing surface of the plasma membrane, which engulfs the antigen, whereas clathrin marks the antigen for phagocytosis by neutrophils. d. Opsonin marks the antigen for phagocytosis by neutrophils, whereas clathrin stabilizes the inward facing surface of the plasma membrane, which engulfs the antigen. SCIENCE PRACTICE CHALLENGE QUESTIONS 39. Membrane fluidity is influenced by the number of C-C double bonds (unsaturation) in the hydrocarbon tails of the lipids composing cell membranes. Fluidity is also dependent on temperature. The transit of materials through the cell membrane is controlled by fluidity. To maintain homeostasis, all organisms, including the simple bacterium E. coli, must sense the temperature of the environment and adapt to changes. Samples of E. coli were grown at four different temperatures, and then researchers determined the fatty acid composition of their plasma membranes. The data are shown in the following table. Growth Temperature (°C) Fatty acid 10 20 30 40 Myristic 17% 14% 14% 16% Palmitic 18% 25% 29% 48% Palmitoleic 26% 24% 23% 9% Oleic 38% 34% 30% 12% Ratio (U/S) Table 5.3 Fatty acid compositions of the plasma membrane of E. coli were incubated at the temperatures shown. Myristic and palmitic acid are saturated, while palmitoleic and oleic acids each have one C-C double bond. A. Analyze the data to calculate the ratio of the fraction of unsaturated (U) to the fraction of saturated (S) fatty acids in the plasma membrane, and complete the table. B. Graph the ratio U/S versus growth temperature. C. Explain the response of E. coli to the temperature of the environment. D. We know that the temperature of the environment is sensed by E. coli through the temperature-dependent confirmation of enzymes that convert a single bond in the lipid tail to a double bond, and vice versa. Explain how the discovery of a mutant strain of E. coli could lead to this insight. TeachingTip: This question connects concepts drawn from Big Ideas 2, 4, and 1. 40. Aquaporins that allow for the movement
of water across a cell membrane are gated. Both low and high pH within a plant cell can cause alterations of the membranespanning protein. Describe the advantage of this feedback mechanism. Predict how conditions of flooding or drought could activate this mechanism. 41. Rice plants grown in high-salt environments can actively transport sodium ions into the vacuole by the antiporter movement of protons out of the vacuole. In a study aimed at the development of salt-tolerant rye, researchers produced several varieties of transgenic rye. Measurements of height and stem diameter for the transgenic varieties (TG1 – TG4) are compared with the wild type varieties WT1 and WT2. Shown in the table below are the mean and standard deviation from measurements of a very large sample size. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 5 \| Structure and Function of Plasma Membranes 235 Variety Height (cm) Stem thickness (cm) WT1 WT2 TG1 TG2 TG3 TG4 9.667±0.333 1.975±0.095 11.867±0.376 2.238±0.204 15.420±1.146 2.723±0.261 15.600±0.909 2.903±0.323 14.925±0.767 2.633±0.073 16.100±0.682 3.160±0.169 Table 5.4 A. Analyze the data. Are the heights and stem thicknesses in the transgenic plants significantly different than in the wild type plant? Justify your claim with evidence. B. Are the heights and stem thicknesses among the transgenic plants significantly different? Justify your claim with evidence. C. Plants from which these data were taken were grown in 10 mM NaCl solutions. Pose one question that researchers can investigate by growing the same varieties in a series of lowersalinity conditions. D. The Na+/H+ antiporter is an active transport system. Briefly explain negative feedback regulation of the movement of sodium into the vacuole of rye cells. 236 Chapter 5 \| Structure and Function of Plasma Membranes This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 237 6 \| METABOLISM Figure 6.1 A humming
bird needs energy to maintain prolonged periods of flight. The bird obtains its energy from taking in food and transforming the nutrients into energy through a series of biochemical reactions. The flight muscles in birds are extremely efficient in energy production. (credit: modification of work by Cory Zanker) Chapter Outline 6.1: Energy and Metabolism 6.2: Potential, Kinetic, Free, and Activation Energy 6.3: The Laws of Thermodynamics 6.4: ATP: Adenosine Triphosphate 6.5: Enzymes Introduction Virtually every task performed by living organisms requires energy. Energy is needed to perform heavy labor and exercise. Humans also use a great deal of energy while thinking and even during sleep. In fact, the living cells of every organism constantly use energy. Nutrients and other molecules are imported, metabolized (broken down), synthesized into new molecules, modified if needed, transported around the cell, and, in some cases, distributed to the entire organism. For example, the large proteins that make up muscles are actively built from smaller molecules. Complex carbohydrates are broken down into simple sugars that the cell uses for energy. Just as energy is required to both build and demolish a building, energy is required for both the synthesis and breakdown of molecules. Additionally, signaling molecules such as hormones and neurotransmitters are actively transported between cells. Pathogenic bacteria and viruses are ingested and broken down by cells. Cells must also export waste and toxins to stay healthy. Many cells swim or move surrounding materials via the beating motion of cellular appendages such as cilia and flagella. All of the cellular processes listed above require a steady supply of energy. From where, and in what form, does this energy come? How do living cells obtain energy and how do they use it? This chapter will discuss different forms of energy and the physical laws that govern energy transfer. How enzymes lower the activation energy required to begin a chemical reaction in the body will also be discussed in this chapter. Enzymes are crucial for life; without them the chemical reactions required to survive would not happen fast enough for an organism to survive. For example, in an individual who lacks one of the enzymes needed to break down a type of carbohydrate known as a mucopolysaccharide, waste products accumulate in the cells and cause progressive brain damage. This deadly genetic disease is called Sanfilippo Syndrome type B or Mucopolysaccharidosis III. Previously incurable, 238 Chapter 6 \| Metabolism scientists
have now discovered a way to replace the missing enzyme in the brain of mice. Read more about the scientists’ research here (http://openstaxcollege.org/l/32mpsiiib). 6.1 \| Energy and Metabolism In this section, you will explore the following questions: • What are metabolic pathways? • What are the differences between anabolic and catabolic pathways? • How do chemical reactions play a role in energy transfer? Connection for AP® Courses All living systems, from simple cells to complex ecosystems, require free energy to conduct cell processes such as growth and reproduction. Organisms have evolved various strategies to capture, store, transform, and transfer free energy. A cell’s metabolism refers to the chemical reactions that occur within it. Some metabolic reactions involve the breaking down of complex molecules into simpler ones with a release of energy (catabolism), whereas other metabolic reactions require energy to build complex molecules (anabolism). A central example of these pathways is the synthesis and breakdown of glucose. The content presented in this section supports the Learning Objectives outlined in Big Idea 1 and Big Idea 2 of the AP® Biology Curriculum Framework listed below. The AP® Learning Objectives merge Essential Knowledge content with one or more of the seven Science Practices. These objectives provide a transparent foundation for the AP® Biology course, along with inquiry-based laboratory experiences, instructional activities, and AP® exam questions. Big Idea 1 The process of evolution drives the diversity and unity of life. Enduring Understanding 1.B Organisms are linked by lines of descent from common ancestry. Essential Knowledge 1.B.1 Organisms share many conserved core processes and features that evolved and are widely distributed among organisms today. Science Practice Learning Objective 3.1 The student can pose scientific questions. 1.14 The student is able to pose scientific questions that correctly identify essential properties of shared, core life processes that provide insight into the history of life on Earth. Essential Knowledge 1.B.1 Organisms share many conserved core processes and features that evolved and are widely distributed among organisms today. Science Practice 7.2 The student can connect concepts in and across domain(s) to generalize or extrapolate in and/or across enduring understandings and/or big ideas. Learning Objective 1.15 The student is able to describe specific examples of conserved core biological processes and features shared by all domains or within one domain of life, and how these shared, conserved core processes and features support
the concept of common ancestry for all organisms. Essential Knowledge 1.B.1 Organisms share many conserved core processes and features that evolved and are widely distributed among organisms today. Science Practice Learning Objective 6.1 The student can justify claims with evidence. 1.16 The student is able to justify the scientific claim that organisms share many conserved core processes and features that evolved and are widely distributed among organisms today. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 239 Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Learning Objective Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and maintenance of living systems require free energy and matter. 2.A.1 All living systems require a constant input of free energy. 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.1 The student is able to explain how biological systems use free energy based on empirical data that all organisms require constant energy input to maintain organization, to grow and to reproduce. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.1][APLO 2.3][APLO 4.3][APLO 4.15][APLO 4.17][APLO 2.21] Scientists use the term bioenergetics to discuss the concept of energy flow (Figure 6.2) through living systems, such as cells. Cellular processes such as the building and breaking down of complex molecules occur through stepwise chemical reactions. Some of these chemical reactions are spontaneous and release energy, whereas others require energy to proceed. Just as living things must continually consume food to replenish what has been used, cells must continually produce more energy to replenish that used by the many energy-requiring chemical reactions that constantly take place. All of the chemical reactions that take place inside cells, including those that use energy and those that release energy, are the cell’s metabolism. Figure 6.2 Most life forms on earth get their energy from the sun. Plants use photosynthesis to capture sunlight, and herbivores eat those plants to obtain energy. Carnivores eat the herbivores, and decomposers digest plant and animal matter. 240 Chapter 6 \| Metabolism Metabolism of Carbohydrates The
metabolism of sugar (a simple carbohydrate) is a classic example of the many cellular processes that use and produce energy. Living things consume sugar as a major energy source, because sugar molecules have a great deal of energy stored within their bonds. The breakdown of glucose, a simple sugar, is described by the equation: C6 H12 O6 + 6O2 → 6CO2 + 6H2 O + energy Carbohydrates that are consumed have their origins in photosynthesizing organisms like plants (Figure 6.3). During photosynthesis, plants use the energy of sunlight to convert carbon dioxide gas (CO2) into sugar molecules, like glucose (C6H12O6). Because this process involves synthesizing a larger, energy-storing molecule, it requires an input of energy to proceed. The synthesis of glucose is described by this equation (notice that it is the reverse of the previous equation): 6CO2 + 6H2 O + energy → C6 H12 O6 + 6O2 During the chemical reactions of photosynthesis, energy is provided in the form of a very high-energy molecule called ATP, or adenosine triphosphate, which is the primary energy currency of all cells. Just as the dollar is used as currency to buy goods, cells use molecules of ATP as energy currency to perform immediate work. The sugar (glucose) is stored as starch or glycogen. Energy-storing polymers like these are broken down into glucose to supply molecules of ATP. Solar energy is required to synthesize a molecule of glucose during the reactions of photosynthesis. In photosynthesis, light energy from the sun is initially transformed into chemical energy that is temporally stored in the energy carrier molecules ATP and NADPH (nicotinamide adenine dinucleotide phosphate). The stored energy in ATP and NADPH is then used later in photosynthesis to build one molecule of glucose from six molecules of CO2. This process is analogous to eating breakfast in the morning to acquire energy for your body that can be used later in the day. Under ideal conditions, energy from 18 molecules of ATP is required to synthesize one molecule of glucose during the reactions of photosynthesis. Glucose molecules can also be combined with and converted into other types of sugars. When sugars are consumed, molecules of glucose eventually make their way into each living cell of the organism. Inside the cell, each sugar molecule is broken down through a complex series of chemical reactions. The goal of these reactions is to harvest the energy stored
inside the sugar molecules. The harvested energy is used to make high-energy ATP molecules, which can be used to perform work, powering many chemical reactions in the cell. The amount of energy needed to make one molecule of glucose from six molecules of carbon dioxide is 18 molecules of ATP and 12 molecules of NADPH (each one of which is energetically equivalent to three molecules of ATP), or a total of 54 ATP molecule equivalents required for the synthesis of one molecule of glucose. This process is a fundamental and efficient way for cells to generate the molecular energy that they require. Figure 6.3 Plants, like this oak tree, use energy from sunlight to make sugar and other organic molecules. Both plants and animals, like this squirrel, use cellular respiration to derive energy from the organic molecules originally produced by plants. Metabolic Pathways The processes of making and breaking down sugar molecules illustrate two types of metabolic pathways. A metabolic pathway is a series of interconnected biochemical reactions that convert a substrate molecule or molecules, step-by-step, through a series of metabolic intermediates, eventually yielding a final product or products. In the case of sugar metabolism, the first metabolic pathway synthesized sugar from smaller molecules, and the other pathway broke sugar down into smaller This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 241 molecules. These two opposite processes—the first requiring energy and the second producing energy—are referred to as anabolic (building) and catabolic (breaking down) pathways, respectively. Consequently, metabolism is composed of building (anabolism) and degradation (catabolism). Figure 6.4 This tree shows the evolution of the various branches of life. The vertical dimension is time. Early life forms, in blue, used anaerobic metabolism to obtain energy from their surroundings. Evolution of Metabolic Pathways There is more to the complexity of metabolism than understanding the metabolic pathways alone. Metabolic complexity varies from organism to organism. Photosynthesis is the primary pathway in which photosynthetic organisms like plants (the majority of global synthesis is done by planktonic algae) harvest the sun’s energy and convert it into carbohydrates. The by-product of photosynthesis is oxygen, required by some cells to carry out cellular respiration. During cellular respiration, oxygen aids in the catabolic breakdown of carbon compounds, like carbohydrates. Among the products of this catabolism are CO2 and ATP. In addition, some e
ukaryotes perform catabolic processes without oxygen (fermentation); that is, they perform or use anaerobic metabolism. Organisms probably evolved anaerobic metabolism to survive (living organisms came into existence about 3.8 billion years ago, when the atmosphere lacked oxygen). Despite the differences between organisms and the complexity of metabolism, researchers have found that all branches of life share some of the same metabolic pathways, suggesting that all organisms evolved from the same ancient common ancestor (Figure 6.4). Evidence indicates that over time, the pathways diverged, adding specialized enzymes to allow organisms to better adapt to their environment, thus increasing their chance to survive. However, the underlying principle remains that all organisms must harvest energy from their environment and convert it to ATP to carry out cellular functions. The early atmosphere lacked oxygen. Why do you think this is the case? a. Oxygen is a byproduct of photosynthesis, so there was very little oxygen in the atmosphere until photosynthetic organisms evolved. b. Oxygen is a byproduct of anaerobic respiration, so there was very little oxygen in the atmosphere until anaerobic organisms evolved. c. Oxygen is a byproduct of fermentation, so there was very little oxygen in the atmosphere until fermentative organisms evolved. Anabolic and Catabolic Pathways Anabolic pathways require an input of energy to synthesize complex molecules from simpler ones. Synthesizing sugar from CO2 is one example. Other examples are the synthesis of large proteins from amino acid building blocks, and the synthesis of new DNA strands from nucleic acid building blocks. These biosynthetic processes are critical to the life of the cell, take place constantly, and demand energy provided by ATP and other high-energy molecules like NADH (nicotinamide adenine 242 Chapter 6 \| Metabolism dinucleotide) and NADPH (Figure 6.5). ATP is an important molecule for cells to have in sufficient supply at all times. The breakdown of sugars illustrates how a single molecule of glucose can store enough energy to make a great deal of ATP, 36 to 38 molecules. This is a catabolic pathway. Catabolic pathways involve the degradation (or breakdown) of complex molecules into simpler ones. Molecular energy stored in the bonds of complex molecules is released in catabolic pathways and harvested in such a way that it can be used to produce ATP. Other energy-storing molecules, such as fats, are also broken down through similar catabolic reactions to release energy and make ATP (Figure 6.5). It
is important to know that the chemical reactions of metabolic pathways don’t take place spontaneously. Each reaction step is facilitated, or catalyzed, by a protein called an enzyme. Enzymes are important for catalyzing all types of biological reactions—those that require energy as well as those that release energy. Figure 6.5 Anabolic pathways are those that require energy to synthesize larger molecules. Catabolic pathways are those that generate energy by breaking down larger molecules. Both types of pathways are required for maintaining the cell’s energy balance. Think About It Describe two different cellular functions in different organisms that require energy that parallel human energyrequiring functions such as physical exercise. Section Summary Cells perform the functions of life through various chemical reactions. A cell’s metabolism refers to the chemical reactions that take place within it. There are metabolic reactions that involve the breaking down of complex chemicals into simpler ones, such as the breakdown of large macromolecules. This process is referred to as catabolism, and such reactions are associated with a release of energy. On the other end of the spectrum, anabolism refers to metabolic processes that build complex molecules out of simpler ones, such as the synthesis of macromolecules. Anabolic processes require energy. Glucose synthesis and glucose breakdown are examples of anabolic and catabolic pathways, respectively. 6.2 \| Potential, Kinetic, Free, and Activation Energy In this section, you will explore the following questions: • What is “energy”? • What is the difference between kinetic and potential energy? • What is free energy, and how does free energy related to activation energy? • What is the difference between endergonic and exergonic reactions? This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 243 Connection for AP® Courses Although cells and organisms require free energy to survive, they cannot spontaneously create energy, as stated in the Law of Conservation of Energy. Energy is available in different forms. For example, objects in motion possess kinetic energy, whereas objects that are not in motion possess potential energy. The chemical energy in molecules, such as glucose, is potential energy because when bonds break in chemical reactions, free energy is released. Free energy is a measure of energy that is available to do work. The free energy of a system changes during energy transfers such as chemical reactions, and this change is referred to as ΔG or Gibbs
free energy. The ΔG of a reaction can be negative or positive, depending on whether the reaction releases energy (exergonic) or requires energy input (endergonic). All reactions require an input of energy called activation energy in order to reach the transition state at which they will proceed. (In another section, we will explore how enzymes speed up chemical reactions by lowering activation energy barriers.) Information presented and the examples highlighted in the section support concepts and Learning Objectives outlined in Big Idea 2 of the AP® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® Exam questions. A Learning Objective merges required content with one or more of the seven Science Practices. Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Learning Objective Essential Knowledge Science Practice Learning Objective Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and maintenance of living systems require free energy and matter. 2.A.1 All living systems require constant input of free energy. 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.1 The student is able to explain how biological systems use free energy based on empirical data that all organisms require constant energy input to maintain organization, to grow, and to reproduce. 2.A.1 All living systems require constant input of free energy. 6.2 The student can justify claims with evidence. 2.2 The student is able to justify a scientific claim that free energy is required for living systems to maintain organization, to grow or to reproduce, but that multiple strategies exist in different living systems. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.5] Energy is defined as the ability to do work. As you’ve learned, energy exists in different forms. For example, electrical energy, light energy, and heat energy are all different types of energy. While these are all familiar types of energy that one can see or feel, there is another type of energy that is much less tangible. This energy is associated with something as simple as an object held above the ground. In order to appreciate the way energy flows into and out of biological systems, it is important to understand more about the different types of energy that exist in the physical
world. Types of Energy When an object is in motion, there is energy associated with that object. In the example of an airplane in flight, there is a great deal of energy associated with the motion of the airplane. This is because moving objects are capable of enacting a change, or doing work. Think of a wrecking ball. Even a slow-moving wrecking ball can do a great deal of damage to other objects. However, a wrecking ball that is not in motion is incapable of performing work. Energy associated with objects in motion is called kinetic energy. A speeding bullet, a walking person, the rapid movement of molecules in the air (which 244 Chapter 6 \| Metabolism produces heat), and electromagnetic radiation like light all have kinetic energy. Now what if that same motionless wrecking ball is lifted two stories above a car with a crane? If the suspended wrecking ball is unmoving, is there energy associated with it? The answer is yes. The suspended wrecking ball has energy associated with it that is fundamentally different from the kinetic energy of objects in motion. This form of energy results from the fact that there is the potential for the wrecking ball to do work. If it is released, indeed it would do work. Because this type of energy refers to the potential to do work, it is called potential energy. Objects transfer their energy between kinetic and potential in the following way: As the wrecking ball hangs motionless, it has 0 kinetic and 100 percent potential energy. Once it is released, its kinetic energy begins to increase because it builds speed due to gravity. At the same time, as it nears the ground, it loses potential energy. Somewhere mid-fall it has 50 percent kinetic and 50 percent potential energy. Just before it hits the ground, the ball has nearly lost its potential energy and has near-maximal kinetic energy. Other examples of potential energy include the energy of water held behind a dam (Figure 6.6), or a person about to skydive out of an airplane. Figure 6.6 Water behind a dam has potential energy. Moving water, such as in a waterfall or a rapidly flowing river, has kinetic energy. (credit “dam”: modification of work by "Pascal"/Flickr; credit “waterfall”: modification of work by Frank Gualtieri) Potential energy is not only associated with the location of matter (such as a child sitting on a tree branch), but also with the structure of matter. A spring on
the ground has potential energy if it is compressed; so does a rubber band that is pulled taut. The very existence of living cells relies heavily on structural potential energy. On a chemical level, the bonds that hold the atoms of molecules together have potential energy. Remember that anabolic cellular pathways require energy to synthesize complex molecules from simpler ones, and catabolic pathways release energy when complex molecules are broken down. The fact that energy can be released by the breakdown of certain chemical bonds implies that those bonds have potential energy. In fact, there is potential energy stored within the bonds of all the food molecules we eat, which is eventually harnessed for use. This is because these bonds can release energy when broken. The type of potential energy that exists within chemical bonds, and is released when those bonds are broken, is called chemical energy (Figure 6.7). Chemical energy is responsible for providing living cells with energy from food. The release of energy is brought about by breaking the molecular bonds within fuel molecules. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 245 Figure 6.7 The molecules in gasoline (octane, the chemical formula shown) contain chemical energy within the chemical bonds. This energy is transformed into kinetic energy that allows a car to race on a racetrack. (credit “car”: modification of work by Russell Trow) Visit this site (http://openstaxcollege.org/l/simple_pendulum) and select “A simple pendulum” on the menu (under “Harmonic Motion”) to see the shifting kinetic (K) and potential energy (U) of a pendulum in motion. Explain how the potential and kinetic energy shown in the pendulum model (http://openstaxcollege.org/l/ simple_pendulum) relates to a child swinging on a swing set. a. Kinetic energy increases when the child swings downward, potential energy increases when the child swings upward. b. Kinetic energy decreases when the child swings downward, potential energy decreases when the child swings upward. c. Kinetic energy increases when the child swings upward, potential energy increases when the child swings downward. d. Kinetic energy increases when child swings downward, potential energy increases when the child swings downward. Free Energy After learning that chemical reactions release energy when energy-storing bonds are broken, an important next question is how is the
energy associated with chemical reactions quantified and expressed? How can the energy released from 246 Chapter 6 \| Metabolism one reaction be compared to that of another reaction? A measurement of free energy is used to quantitate these energy transfers. Free energy is called Gibbs free energy (abbreviated with the letter G) after Josiah Willard Gibbs, the scientist who developed the measurement. Recall that according to the second law of thermodynamics, all energy transfers involve the loss of some amount of energy in an unusable form such as heat, resulting in entropy. Gibbs free energy specifically refers to the energy associated with a chemical reaction that is available after entropy is accounted for. In other words, Gibbs free energy is usable energy, or energy that is available to do work. Every chemical reaction involves a change in free energy, called delta G (∆G). The change in free energy can be calculated for any system that undergoes such a change, such as a chemical reaction. To calculate ∆G, subtract the amount of energy lost to entropy (denoted as ∆S) from the total energy change of the system. This total energy change in the system is called enthalpy and is denoted as ∆H. The formula for calculating ∆G is as follows, where the symbol T refers to absolute temperature in Kelvin (degrees Celsius + 273): ΔG = ΔH − TΔS The standard free energy change of a chemical reaction is expressed as an amount of energy per mole of the reaction product (either in kilojoules or kilocalories, kJ/mol or kcal/mol; 1 kJ = 0.239 kcal) under standard pH, temperature, and pressure conditions. Standard pH, temperature, and pressure conditions are generally calculated at pH 7.0 in biological systems, 25 degrees Celsius, and 100 kilopascals (1 atm pressure), respectively. It is important to note that cellular conditions vary considerably from these standard conditions, and so standard calculated ∆G values for biological reactions will be different inside the cell. Endergonic Reactions and Exergonic Reactions If energy is released during a chemical reaction, then the resulting value from the above equation will be a negative number. In other words, reactions that release energy have a ∆G < 0. A negative ∆G also means that the products of the reaction have less free energy than the reactants, because they gave off some free energy during the reaction. Reactions that have a negative ∆
G and consequently release free energy are called exergonic reactions. Think: exergonic means energy is exiting the system. These reactions are also referred to as spontaneous reactions, because they can occur without the addition of energy into the system. Understanding which chemical reactions are spontaneous and release free energy is extremely useful for biologists, because these reactions can be harnessed to perform work inside the cell. An important distinction must be drawn between the term spontaneous and the idea of a chemical reaction that occurs immediately. Contrary to the everyday use of the term, a spontaneous reaction is not one that suddenly or quickly occurs. The rusting of iron is an example of a spontaneous reaction that occurs slowly, little by little, over time. If a chemical reaction requires an input of energy rather than releasing energy, then the ∆G for that reaction will be a positive value. In this case, the products have more free energy than the reactants. Thus, the products of these reactions can be thought of as energy-storing molecules. These chemical reactions are called endergonic reactions, and they are nonspontaneous. An endergonic reaction will not take place on its own without the addition of free energy. Let’s revisit the example of the synthesis and breakdown of the food molecule, glucose. Remember that the building of complex molecules, such as sugars, from simpler ones is an anabolic process and requires energy. Therefore, the chemical reactions involved in anabolic processes are endergonic reactions. On the other hand, the catabolic process of breaking sugar down into simpler molecules releases energy in a series of exergonic reactions. Like the example of rust above, the breakdown of sugar involves spontaneous reactions, but these reactions don’t occur instantaneously. Figure 6.8 shows some other examples of endergonic and exergonic reactions. Later sections will provide more information about what else is required to make even spontaneous reactions happen more efficiently. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 247 Figure 6.8 Shown are some examples of endergonic processes (ones that require energy) and exergonic processes (ones that release energy). These include (a) a compost pile decomposing, (b) a chick developing from a fertilized egg, (c) sand art being destroyed, and (d) a ball rolling down a hill. (credit a: modification of work by Natalie Maynor; credit
b: modification of work by USDA; credit c: modification of work by “Athlex”/Flickr; credit d: modification of work by Harry Malsch) 248 Chapter 6 \| Metabolism Look at each of the processes shown, and decide if it is endergonic or exergonic. In each case, does enthalpy increase or decrease, and does entropy increase or decrease? a. Compost pile decomposition is endergonic, enthalpy increases and entropy increases. A baby developing from egg is an endergonic process, enthalpy decreases and entropy decreases. Sand art being destroyed is exergonic, no change in enthalpy and entropy increases. A ball rolling downhill is exergonic process, enthalpy decreases and no change in entropy. b. Compost pile decomposition is exergonic, enthalpy increases and entropy increases. A baby developing from egg is an endergonic process, enthalpy decreases and entropy decreases. Sand art being destroyed is exergonic, no change in enthalpy and entropy decreases. A ball rolling downhill is exergonic process, enthalpy decreases and no change in entropy. c. Compost pile decomposition is exergonic, enthalpy increases and entropy increases. A baby developing from egg is an endergonic process, enthalpy decreases and entropy decreases. Sand art being destroyed is exergonic, no change in enthalpy and entropy increases. A ball rolling downhill is exergonic process, enthalpy decreases and entropy increases. d. A ball rolling down the hill doesn’t affect the order of system; therefore, the entropy would remain unchanged. An important concept in the study of metabolism and energy is that of chemical equilibrium. Most chemical reactions are reversible. They can proceed in both directions, releasing energy into their environment in one direction, and absorbing it from the environment in the other direction (Figure 6.9). The same is true for the chemical reactions involved in cell metabolism, such as the breaking down and building up of proteins into and from individual amino acids, respectively. Reactants within a closed system will undergo chemical reactions in both directions until a state of equilibrium is reached. This state of equilibrium is one of the lowest possible free energy and a state of maximal entropy. Energy must be put into the system to push the reactants and products away from a state of equilibrium. Either reactants or products must This OpenStax book is available for free at http://cn
x.org/content/col12078/1.6 Chapter 6 \| Metabolism 249 be added, removed, or changed. If a cell were a closed system, its chemical reactions would reach equilibrium, and it would die because there would be insufficient free energy left to perform the work needed to maintain life. In a living cell, chemical reactions are constantly moving towards equilibrium, but never reach it. This is because a living cell is an open system. Materials pass in and out, the cell recycles the products of certain chemical reactions into other reactions, and chemical equilibrium is never reached. In this way, living organisms are in a constant energy-requiring, uphill battle against equilibrium and entropy. This constant supply of energy ultimately comes from sunlight, which is used to produce nutrients in the process of photosynthesis. Figure 6.9 Exergonic and endergonic reactions result in changes in Gibbs free energy. Exergonic reactions release energy; endergonic reactions require energy to proceed. Activation Energy There is another important concept that must be considered regarding endergonic and exergonic reactions. Even exergonic reactions require a small amount of energy input to get going before they can proceed with their energy-releasing steps. These reactions have a net release of energy, but still require some energy in the beginning. This small amount of energy input necessary for all chemical reactions to occur is called the activation energy (or free energy of activation) and is abbreviated EA (Figure 6.10). Why would an energy-releasing, negative ∆G reaction actually require some energy to proceed? The reason lies in the steps that take place during a chemical reaction. During chemical reactions, certain chemical bonds are broken and new ones are formed. For example, when a glucose molecule is broken down, bonds between the carbon atoms of the molecule are broken. Since these are energy-storing bonds, they release energy when broken. However, to get them into a state that allows the bonds to break, the molecule must be somewhat contorted. A small energy input is required to achieve this contorted state. This contorted state is called the transition state, and it is a high-energy, unstable state. For this reason, reactant molecules don’t last long in their transition state, but very quickly proceed to the next steps of the chemical reaction. Free energy diagrams illustrate the energy profiles for a given reaction. Whether the reaction is exergonic or endergonic determines whether the products in the diagram will exist
at a lower or higher energy state than both the reactants and the products. However, regardless of this measure, the transition state of the reaction exists at a higher energy state than the reactants, and thus, EA is always positive. 250 Chapter 6 \| Metabolism Watch an animation of energy_reaction) site. the move from free energy to transition state at this (http://openstaxcollege.org/l/ Explain why transitional states are unstable. a. Molecules have relaxed molecular structure with low energy. b. Molecules have strained molecular structure with high energy. c. Molecules have relaxed molecular structure with high energy. d. Molecules have strained molecular structure with low energy. Where does the activation energy required by chemical reactants come from? The source of the activation energy needed to push reactions forward is typically heat energy from the surroundings. Heat energy (the total bond energy of reactants or products in a chemical reaction) speeds up the motion of molecules, increasing the frequency and force with which they collide; it also moves atoms and bonds within the molecule slightly, helping them reach their transition state. For this reason, heating up a system will cause chemical reactants within that system to react more frequently. Increasing the pressure on a system has the same effect. Once reactants have absorbed enough heat energy from their surroundings to reach the transition state, the reaction will proceed. The activation energy of a particular reaction determines the rate at which it will proceed. The higher the activation energy, the slower the chemical reaction will be. The example of iron rusting illustrates an inherently slow reaction. This reaction occurs slowly over time because of its high EA. Additionally, the burning of many fuels, which is strongly exergonic, will take place at a negligible rate unless their activation energy is overcome by sufficient heat from a spark. Once they begin to burn, however, the chemical reactions release enough heat to continue the burning process, supplying the activation energy for surrounding fuel molecules. Like these reactions outside of cells, the activation energy for most cellular reactions is too high for heat energy to overcome at efficient rates. In other words, in order for important cellular reactions to occur at appreciable rates (number of reactions per unit time), their activation energies must be lowered (Figure 6.10); this is referred to as catalysis. This is a very good thing as far as living cells are concerned. Important macromolecules, such as proteins, DNA, and RNA, store considerable energy, and their breakdown is exergonic. If
cellular temperatures alone provided enough heat energy for these exergonic reactions to overcome their activation barriers, the essential components of a cell would disintegrate. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 251 Figure 6.10 Activation energy is the energy required for a reaction to proceed, and it is lower if the reaction is catalyzed. The horizontal axis of this diagram describes the sequence of events in time. How does the change in Gibbs free energy (ΔG) differ between the catalyzed versus uncatalyzed reaction? a. ΔG is greater for the forward direction than for the reverse direction. b. ΔG is greater for the uncatalyzed than the catalyzed reaction. c. ΔG is greater for the catalyzed than the uncatalyzed reaction. d. ΔG is the same for the catalyzed and uncatalyzed reactions. Think About It All plants use water, carbon dioxide, and energy from the sun to make sugars. Think about what would happen to plants that do not have sunlight as an energy source or sufficient water. What would happen to organisms that depend on those plants for their own survival? How does depletion or destruction of forests by human activity affect free energy availability to organisms living in the rain forest? What measures can be taken to try and restore the free energy to an acceptable level? Section Summary Energy comes in many different forms. Objects in motion do physical work, and kinetic energy is the energy of objects in motion. Objects that are not in motion may have the potential to do work, and thus, have potential energy. Molecules also have potential energy because the breaking of molecular bonds has the potential to release energy. Living cells depend on the harvesting of potential energy from molecular bonds to perform work. Free energy is a measure of energy that is available to do work. The free energy of a system changes during energy transfers such as chemical reactions, and this change is referred to as ∆G. The ∆G of a reaction can be negative or positive, meaning that the reaction releases energy or consumes energy, respectively. A reaction with a negative ∆G that gives off energy is called an exergonic reaction. One with a positive ∆G that requires energy input is called an endergonic reaction. Exergonic reactions are said to be spontaneous, because their products have less energy than their reactants. The products of endergonic reactions have a
higher energy state than the reactants, and so 252 Chapter 6 \| Metabolism these are nonspontaneous reactions. However, all reactions (including spontaneous –∆G reactions) require an initial input of energy in order to reach the transition state, at which they’ll proceed. This initial input of energy is called the activation energy. 6.3 \| The Laws of Thermodynamics In this section, you will explore the following questions: • What is entropy? • What is the difference between the first and second laws of thermodynamics? Connection for AP® Courses In studying energy, scientists use the term system to refer to the matter and its environment involved in energy transfers, such as an ecosystem. Even single cells are biological systems and all systems require energy to maintain order. The more ordered a system is, the lower its entropy. Entropy is a measure of the disorder of the system. (Think of your bedroom as a system. On Sunday evening, you throw dirty clothes in the laundry basket, put books back on the shelves, and return dirty dishes to the kitchen. Cleaning your room requires an input of energy. What gradually happens as the week progresses? You guessed it: entropy.) All biological systems obey the laws of chemistry and physics, including the laws of thermodynamics that describe the properties and processes of energy transfer in systems. The first law states that the total amount of energy in the universe is constant; energy cannot be created or destroyed, but it can be transformed and transferred. The second law states that every energy transfer involves some loss of energy in an unusable form, such as heat energy, resulting in a more disordered system (e.g., your bedroom over the course of a week). Thus, no energy transfer is completely efficient. (We will explore how free energy is stored, transferred, and used in more detail when we study photosynthesis and cellular respiration.) Information presented and the examples highlighted in the section, support concepts and Learning Objectives outlined in Big Idea 2 of the AP® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® Exam questions. A Learning Objective merges required content with one or more of the seven Science Practices. Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Learning Objective Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth
, reproduction and maintenance of living systems require free energy and matter. 2.A.1 All living systems require constant input of free energy. 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.1 The student is able to explain how biological systems use free energy based on empirical data that all organisms require constant energy input to maintain organization, to grow, and to reproduce. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.1][APLO 2.2][APLO 2.4][APLO 4.16][APLO 2.3] Thermodynamics refers to the study of energy and energy transfer involving physical matter. The matter and its environment relevant to a particular case of energy transfer are classified as a system, and everything outside of that system is called the surroundings. For instance, when heating a pot of water on the stove, the system includes the stove, the pot, and the water. Energy is transferred within the system (between the stove, pot, and water). There are two types of systems: open This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 253 and closed. An open system is one in which energy can be transferred between the system and its surroundings. The stovetop system is open because heat can be lost into the air. A closed system is one that cannot transfer energy to its surroundings. Biological organisms are open systems. Energy is exchanged between them and their surroundings, as they consume energystoring molecules and release energy to the environment by doing work. Like all things in the physical world, energy is subject to the laws of physics. The laws of thermodynamics govern the transfer of energy in and among all systems in the universe. The First Law of Thermodynamics The first law of thermodynamics deals with the total amount of energy in the universe. It states that this total amount of energy is constant. In other words, there has always been, and always will be, exactly the same amount of energy in the universe. Energy exists in many different forms. According to the first law of thermodynamics, energy may be transferred from place to place or transformed into different forms, but it cannot be created or destroyed. The transfers and transformations of energy take place around us all the time. Light bulbs transform electrical energy into light energy. Gas
stoves transform chemical energy from natural gas into heat energy. Plants perform one of the most biologically useful energy transformations on earth: that of converting the energy of sunlight into the chemical energy stored within organic molecules, as shown in Figure 6.2. Some examples of energy transformations are shown in Figure 6.11. The challenge for all living organisms is to obtain energy from their surroundings in forms that they can transfer or transform into usable energy to do work. Living cells have evolved to meet this challenge very well. Chemical energy stored within organic molecules such as sugars and fats is transformed through a series of cellular chemical reactions into energy within molecules of ATP. Energy in ATP molecules is easily accessible to do work. Examples of the types of work that cells need to do include building complex molecules, transporting materials, powering the beating motion of cilia or flagella, contracting muscle fibers to create movement, and reproduction. Figure 6.11 Shown are two examples of energy being transferred from one system to another and transformed from one form to another. Humans can convert the chemical energy in food, like this ice cream cone, into kinetic energy (the energy of movement to ride a bicycle). Plants can convert electromagnetic radiation (light energy) from the sun into chemical energy. (credit “ice cream”: modification of work by D. Sharon Pruitt; credit “kids on bikes”: modification of work by Michelle Riggen-Ransom; credit “leaf”: modification of work by Cory Zanker) The Second Law of Thermodynamics A living cell’s primary tasks of obtaining, transforming, and using energy to do work may seem simple. However, 254 Chapter 6 \| Metabolism the second law of thermodynamics explains why these tasks are harder than they appear. None of the energy transfers we’ve discussed, along with all energy transfers and transformations in the universe, is completely efficient. In every energy transfer, some amount of energy is lost in a form that is unusable. In most cases, this form is heat energy. Thermodynamically, heat energy is defined as the energy transferred from one system to another that is not doing work. For example, when an airplane flies through the air, some of the energy of the flying plane is lost as heat energy due to friction with the surrounding air. This friction actually heats the air by temporarily increasing the speed of air molecules. Likewise, some energy is lost as heat energy during cellular metabolic reactions. This is good for warm-blooded creatures like us, because
heat energy helps to maintain our body temperature. Strictly speaking, no energy transfer is completely efficient, because some energy is lost in an unusable form. An important concept in physical systems is that of order and disorder (also known as randomness). The more energy that is lost by a system to its surroundings, the less ordered and more random the system is. Scientists refer to the measure of randomness or disorder within a system as entropy. High entropy means high disorder and low energy (Figure 6.12). To better understand entropy, think of a student’s bedroom. If no energy or work were put into it, the room would quickly become messy. It would exist in a very disordered state, one of high entropy. Energy must be put into the system, in the form of the student doing work and putting everything away, in order to bring the room back to a state of cleanliness and order. This state is one of low entropy. Similarly, a car or house must be constantly maintained with work in order to keep it in an ordered state. Left alone, the entropy of the house or car gradually increases through rust and degradation. Molecules and chemical reactions have varying amounts of entropy as well. For example, as chemical reactions reach a state of equilibrium, entropy increases, and as molecules at a high concentration in one place diffuse and spread out, entropy also increases. Transfer of Energy and the Resulting Entropy Set up a simple experiment to understand how energy is transferred and how a change in entropy results. 1. Take a block of ice. This is water in solid form, so it has a high structural order. This means that the molecules cannot move very much and are in a fixed position. The temperature of the ice is 0°C. As a result, the entropy of the system is low. 2. Allow the ice to melt at room temperature. What is the state of molecules in the liquid water now? How did the energy transfer take place? Is the entropy of the system higher or lower? Why? 3. Heat the water to its boiling point. What happens to the entropy of the system when the water is heated? All physical systems can be thought of in this way: Living things are highly ordered, requiring constant energy input to be maintained in a state of low entropy. As living systems take in energy-storing molecules and transform them through chemical reactions, they lose some amount of usable energy in the process, because no reaction is completely efficient. They also produce waste and by-products
that aren’t useful energy sources. This process increases the entropy of the system’s surroundings. Since all energy transfers result in the loss of some usable energy, the second law of thermodynamics states that every energy transfer or transformation increases the entropy of the universe. Even though living things are highly ordered and maintain a state of low entropy, the entropy of the universe in total is constantly increasing due to the loss of usable energy with each energy transfer that occurs. Essentially, living things are in a continuous uphill battle against this constant increase in universal entropy. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 255 Figure 6.12 Entropy is a measure of randomness or disorder in a system. Gases have higher entropy than liquids, and liquids have higher entropy than solids. Think About It • Imagine a large ant colony with an elaborate nest, containing many tunnels and passageways. Now imagine that an earthquake shakes the ground and demolishes the nest. Did the ant nest have higher entropy before or after the earthquake? What can the ants do to restore their nest to close to its original amount of entropy? Explain your answers. • Energy transfers take place constantly in everyday activities. Think of two scenarios: cooking on a stove and driving a car. Explain how the second law of thermodynamics applies to these two scenarios. Section Summary In studying energy, scientists use the term “system” to refer to the matter and its environment involved in energy transfers. Everything outside of the system is called the surroundings. Single cells are biological systems. Systems can be thought of as having a certain amount of order. It takes energy to make a system more ordered. The more ordered a system is, the lower its entropy. Entropy is a measure of the disorder of a system. As a system becomes more disordered, the lower its energy and the higher its entropy become. A series of laws, called the laws of thermodynamics, describe the properties and processes of energy transfer. The first law states that the total amount of energy in the universe is constant. This means that energy can’t be created or destroyed, only transferred or transformed. The second law of thermodynamics states that every energy transfer involves some loss of energy in an unusable form, such as heat energy, resulting in a more disordered system. In other words, no energy transfer is completely efficient and tends toward disorder. 6.4 \| ATP:
Adenosine Triphosphate In this section, you will explore the following questions: • Why is ATP considered the energy currency of the cell? • How is energy released through the hydrolysis of ATP? 256 Chapter 6 \| Metabolism Connection for AP® Courses Adenosine triphosphate or ATP is the energy “currency” or carrier of the cell. When cells require an input of energy, they use ATP. An ATP nucleotide molecule consists of a five-carbon sugar, the nitrogenous base adenine, and three phosphate groups. (Do not confuse ATP with the nucleotides of DNA and RNA, although they have structural similarities.) The bonds that connect the phosphate have high-energy content, and the energy released from the hydrolysis of ATP to ADP + Pi (Adenosine Diphosphate + Pyrophosphate) is used to perform cellular work, such as contracting a muscle or pumping a solute across a cell membrane in active transport. Cells use ATP by coupling the exergonic reaction of ATP hydrolysis with endergonic reactions, with ATP donating its phosphate group to another molecule via a process called phosphorylation. The phosphorylated molecule is at a higher energy state and is less stable than its unphosphorylated form and free energy is released to substrates to perform work during this process. Phosphorylation is an example of energy transfer between molecules. Information presented and the examples highlighted in the section support concepts and Learning Objectives outlined in Big Idea 2 of the AP® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® Exam questions. A Learning Objective merges required content with one or more of the seven Science Practices. Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Learning Objective Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and maintenance of living systems require free energy and matter. 2.A.1 All living systems require constant input of free energy. 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.1 The student is able to explain how biological systems use free energy based on empirical data that all organisms require constant energy input to maintain organization, to grow, and to reproduce. The Science Practices Assessment Ancillary contains additional
test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.2][APLO 4.14][APLO 2.7][APLO 2.35] Even exergonic, energy-releasing reactions require a small amount of activation energy in order to proceed. However, consider endergonic reactions, which require much more energy input, because their products have more free energy than their reactants. Within the cell, where does energy to power such reactions come from? The answer lies with an energysupplying molecule called adenosine triphosphate, or ATP. ATP is a small, relatively simple molecule (Figure 6.13), but within some of its bonds, it contains the potential for a quick burst of energy that can be harnessed to perform cellular work. This molecule can be thought of as the primary energy currency of cells in much the same way that money is the currency that people exchange for things they need. ATP is used to power the majority of energy-requiring cellular reactions. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 257 Figure 6.13 ATP is the primary energy currency of the cell. It has an adenosine backbone with three phosphate groups attached. As its name suggests, adenosine triphosphate is comprised of adenosine bound to three phosphate groups (Figure 6.13). Adenosine is a nucleoside consisting of the nitrogenous base adenine and a five-carbon sugar, ribose. The three phosphate groups, in order of closest to furthest from the ribose sugar, are labeled alpha, beta, and gamma. Together, these chemical groups constitute an energy powerhouse. However, not all bonds within this molecule exist in a particularly high-energy state. Both bonds that link the phosphates are equally high-energy bonds ( phosphoanhydride bonds) that, when broken, release sufficient energy to power a variety of cellular reactions and processes. These high-energy bonds are the bonds between the second and third (or beta and gamma) phosphate groups and between the first and second phosphate groups. The reason that these bonds are considered “high-energy” is because the products of such bond breaking—adenosine diphosphate (ADP) and one inorganic phosphate group (Pi)—have considerably lower free energy than the reactants:
ATP and a water molecule. Because this reaction takes place with the use of a water molecule, it is considered a hydrolysis reaction. In other words, ATP is hydrolyzed into ADP in the following reaction: ATP + H2 O → ADP + Pi + free energy Like most chemical reactions, the hydrolysis of ATP to ADP is reversible. The reverse reaction regenerates ATP from ADP + Pi. Indeed, cells rely on the regeneration of ATP just as people rely on the regeneration of spent money through some sort of income. Since ATP hydrolysis releases energy, ATP regeneration must require an input of free energy. The formation of ATP is expressed in this equation: ADP + Pi + free energy → ATP + H2 O Two prominent questions remain with regard to the use of ATP as an energy source. Exactly how much free energy is released with the hydrolysis of ATP, and how is that free energy used to do cellular work? The calculated ∆G for the hydrolysis of one mole of ATP into ADP and Pi is −7.3 kcal/mole (−30.5 kJ/mol). Since this calculation is true under standard conditions, it would be expected that a different value exists under cellular conditions. In fact, the ∆G for the hydrolysis of one mole of ATP in a living cell is almost double the value at standard conditions: -14 kcal/mol (−57 kJ/mol). ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP + Pi, and the free energy released during this process is lost as heat. The second question posed above, that is, how the energy released by ATP hydrolysis is used to perform work inside the cell, depends on a strategy called energy coupling. Cells couple the exergonic reaction of ATP hydrolysis with endergonic reactions, allowing them to proceed. One example of energy coupling using ATP involves a transmembrane ion pump that is extremely important for cellular function. This sodium-potassium pump (Na+/K+ pump) drives sodium out of the cell and potassium into the cell (Figure 6.14). A large percentage of a cell’s ATP is spent powering this pump, because cellular processes bring a great deal of sodium into the cell and potassium out of the cell. The pump works constantly to stabilize cellular concentrations of sodium and potassium. In order for the pump to turn one cycle (exporting three Na+
ions and importing two K+ ions), one molecule of ATP must be hydrolyzed. When ATP is hydrolyzed, its gamma phosphate doesn’t simply float away, but is actually transferred onto the pump protein. This process of a phosphate group binding to a molecule is called phosphorylation. As with most cases of ATP hydrolysis, a phosphate from ATP is transferred onto another molecule. In a phosphorylated state, the Na+/K+ pump has more free energy and is triggered to undergo a conformational change. This change allows it to release Na+ to the outside of the cell. It then binds extracellular K+, which, through another conformational change, causes the phosphate to detach from the pump. This release of phosphate triggers the K+ to be released to the inside of the cell. Essentially, the energy released from the hydrolysis of ATP is coupled with the energy required to power the pump and transport Na+ and K+ ions. ATP performs cellular work using this basic form of energy coupling through phosphorylation. 258 Chapter 6 \| Metabolism Figure 6.14 The sodium-potassium pump is an example of energy coupling. The energy derived from exergonic ATP hydrolysis is used to pump sodium and potassium ions across the cell membrane. The hydrolysis of one ATP molecule releases 7.3 kcal/mol of energy (ΔG = −7.3 kcal/mol of energy ). If it takes 2.1 kcal/mol of energy to move one Na+ across the membrane (ΔG = +2.1 kcal/mol of energy ), what is the maximum number of sodium ions that could be moved by the hydrolysis of one ATP molecule? a. b. c. d. five four three two Often during cellular metabolic reactions, such as the synthesis and breakdown of nutrients, certain molecules must be altered slightly in their conformation to become substrates for the next step in the reaction series. One example is during the very first steps of cellular respiration, when a molecule of the sugar glucose is broken down in the process of glycolysis. In the first step of this process, ATP is required for the phosphorylation of glucose, creating a high-energy but unstable intermediate. This phosphorylation reaction powers a conformational change that allows the phosphorylated glucose molecule to be converted to the phosphorylated sugar fructose. Fructose is a necessary intermediate for glycolysis to move forward. Here, the exerg
onic reaction of ATP hydrolysis is coupled with the endergonic reaction of converting glucose into a phosphorylated intermediate in the pathway. Once again, the energy released by breaking a phosphate bond within ATP was used for the phosphorylation of another molecule, creating an unstable intermediate and powering an important conformational change. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 259 See an interactive animation of the ATP-producing glycolysis process at glycolysis_stgs). this site (http://openstaxcollege.org/l/ Explain why the lock-and-key model does not adequately represent the relationship between hexokinase and glucose. a. Hexokinase changes conformation in presence of glucose b. Hexokinase induces change in the glucose structure c. Hexokinase requires an effector molecule to bind at allosteric site d. Hexokinase binds glucose without any conformational change Think About It The hydrolysis of one ATP molecules releases 7.3 kcal/mol of energy (ΔG = –7.3 kcal/mol energy). If it takes 2.1 kcal/ mol of energy to move one Na+ across the membrane (ΔG = +2.1 kcal/mol of energy), how many sodium ions could be moved by the hydrolysis of one ATP molecule? Section Summary ATP is the primary energy-supplying molecule for living cells. ATP is made up of a nucleotide, a five-carbon sugar, and three phosphate groups. The bonds that connect the phosphates (phosphoanhydride bonds) have high-energy content. The energy released from the hydrolysis of ATP into ADP + Pi is used to perform cellular work. Cells use ATP to perform work by coupling the exergonic reaction of ATP hydrolysis with endergonic reactions. ATP donates its phosphate group to another molecule via a process known as phosphorylation. The phosphorylated molecule is at a higher-energy state and is less stable than its unphosphorylated form, and this added energy from the addition of the phosphate allows the molecule to undergo its endergonic reaction. 6.5 \| Enzymes In this section, you will explore the following questions: • What is the role of enzymes in metabolic pathways? • How do enzymes function as molecular catalysts? Connection for AP® Courses Many chemical reactions in
cells occur spontaneously, but happen too slowly to meet the needs of a cell. For example, a teaspoon of sucrose (table sugar), a disaccharide, in a glass of iced tea will take time to break down into two monosaccharides, glucose and fructose; however, if you add a small amount of the enzyme sucrase to the tea, sucrose breaks down almost immediately. Sucrase is an example of an enzyme, a type of biological catalyst. Enzymes are 260 Chapter 6 \| Metabolism macromolecules—most often proteins—that speed up chemical reactions by lowering activation energy barriers. Enzymes are very specific for the reactions they catalyze; because they are polypeptides, enzymes can have a variety of shapes attributed to interactions among amino acid R-groups. One part of the enzyme, the active site, interacts with the substrate via the induced fit model of interaction. Substrate binding alters the shape of the enzyme to facilitate the chemical reaction in several different ways, including bringing substrates together in an optimal orientation. After the reaction finishes, the product(s) are released, and the active site returns to its original shape. Enzyme activity, and thus the rate of an enzyme-catalyzed reaction, is regulated by environmental conditions, including the amount of substrate, temperature, pH, and the presence of coenzymes, cofactors, activators, and inhibitors. Inhibitors, coenzymes, and cofactors can act competitively by binding to the enzyme’s active site, or noncompetitively by binding to the enzyme’s allosteric site. An allosteric site is an alternate part of the enzyme that can bind to non–substrate molecules. Enzymes work most efficiently under optimal conditions that are specific to the enzyme. For example, trypsin, an enzyme in the human small intestine, works most efficiently at pH 8, whereas pepsin in the stomach works best under acidic conditions. Sometimes environmental factors, especially low pH and high temperatures, alter the shape of the active site; if the shape cannot be restored, the enzyme denatures. The most common method of enzyme regulation in metabolic pathways is via feedback inhibition. How can various factors, such as feedback inhibition, regulate enzyme activity? Information presented and the examples highlighted in the section support concepts and Learning Objectives outlined in Big Idea 4 of the AP® Biology Curriculum Framework. The learning objectives listed in the Curriculum Framework provide
a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® Exam questions. A Learning Objective merges required content with one or more of the seven science practices. Big Idea 4 Enduring Understanding 4.B Biological systems interact, and these systems and their interactions possess complex properties. Competition and cooperation are important aspects of biological systems. Essential Knowledge 4.B.1 Interactions between molecules affect their structure and function. Science Practice 5.1 The student can analyze data to identify patterns or relationships. Learning Objective 4.17 The student is able to analyze data to identify how molecular interactions affect structure and function. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.15][APLO 4.8][APLO 2.16] A substance that helps a chemical reaction to occur is a catalyst, and the special molecules that catalyze biochemical reactions are called enzymes. Almost all enzymes are proteins, made up of chains of amino acids, and they perform the critical task of lowering the activation energies of chemical reactions inside the cell. Enzymes do this by binding to the reactant molecules, and holding them in such a way as to make the chemical bond-breaking and bond-forming processes take place more readily. It is important to remember that enzymes don’t change the ∆G of a reaction. In other words, they don’t change whether a reaction is exergonic (spontaneous) or endergonic. This is because they don’t change the free energy of the reactants or products. They only reduce the activation energy required to reach the transition state (Figure 6.15). This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 261 Figure 6.15 Enzymes lower the activation energy of the reaction but do not change the free energy of the reaction. Enzyme Active Site and Substrate Specificity The chemical reactants to which an enzyme binds are the enzyme’s substrates. There may be one or more substrates, depending on the particular chemical reaction. In some reactions, a single-reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule. Two reactants might also enter a reaction, both become modified, and leave the reaction as
two products. The location within the enzyme where the substrate binds is called the enzyme’s active site. The active site is where the “action” happens, so to speak. Since enzymes are proteins, there is a unique combination of amino acid residues (also called side chains, or R groups) within the active site. Each residue is characterized by different properties. Residues can be large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral. The unique combination of amino acid residues, their positions, sequences, structures, and properties, creates a very specific chemical environment within the active site. This specific environment is suited to bind, albeit briefly, to a specific chemical substrate (or substrates). Due to this jigsaw puzzle-like match between an enzyme and its substrates (which adapts to find the best fit between the transition state and the active site), enzymes are known for their specificity. The “best fit” results from the shape and the amino acid functional group’s attraction to the substrate. There is a specifically matched enzyme for each substrate and, thus, for each chemical reaction; however, there is flexibility as well. The fact that active sites are so perfectly suited to provide specific environmental conditions also means that they are subject to influences by the local environment. It is true that increasing the environmental temperature generally increases reaction rates, enzyme-catalyzed or otherwise. However, increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the active site in such a way that they are less well suited to bind substrates. High temperatures will eventually cause enzymes, like other biological molecules, to denature, a process that changes the natural properties of a substance. Likewise, the pH of the local environment can also affect enzyme function. Active site amino acid residues have their own acidic or basic properties that are optimal for catalysis. These residues are sensitive to changes in pH that can impair the way substrate molecules bind. Enzymes are suited to function best within a certain pH range, and, as with temperature, extreme pH values (acidic or basic) of the environment can cause enzymes to denature. Induced Fit and Enzyme Function For many years, scientists thought that enzyme-substrate binding took place in a simple “lock-and-key” fashion. This model asserted that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view called induced fit
(Figure 6.16). The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that confirms an ideal binding arrangement between the enzyme and the transition state of the substrate. This ideal binding maximizes the enzyme’s ability to catalyze its reaction. 262 Chapter 6 \| Metabolism View an animation of induced fit at this website (http://openstaxcollege.org/l/hexokinase). Phosphofructokinase deficiency occurs when a person lacks an enzyme needed to perform glycolysis in skeletal muscles. What effect could this have on the body? a. Production of energy by glycolysis will occur, skeletal muscles will function properly b. Production of energy by glycolysis will not occur, skeletal muscles will function properly c. Production of energy by glycolysis will occur, skeletal muscles will not function properly d. Production of energy will not occur, skeletal muscles will not function properly When an enzyme binds its substrate, an enzyme-substrate complex is formed. This complex lowers the activation energy of the reaction and promotes its rapid progression in one of many ways. On a basic level, enzymes promote chemical reactions that involve more than one substrate by bringing the substrates together in an optimal orientation. The appropriate region (atoms and bonds) of one molecule is juxtaposed to the appropriate region of the other molecule with which it must react. Another way in which enzymes promote the reaction of their substrates is by creating an optimal environment within the active site for the reaction to occur. Certain chemical reactions might proceed best in a slightly acidic or non-polar environment. The chemical properties that emerge from the particular arrangement of amino acid residues within an active site create the perfect environment for an enzyme’s specific substrates to react. You’ve learned that the activation energy required for many reactions includes the energy involved in manipulating or slightly contorting chemical bonds so that they can easily break and allow others to reform. Enzymatic action can aid this process. The enzyme-substrate complex can lower the activation energy by contorting substrate molecules in such a way as to facilitate bond-breaking, helping to reach the transition state. Finally, enzymes can also lower activation energies by taking part in the chemical reaction itself. The amino acid residues can provide certain ions or chemical groups that actually form covalent bonds with substrate
molecules as a necessary step of the reaction process. In these cases, it is important to remember that the enzyme will always return to its original state at the completion of the reaction. One of the hallmark properties of enzymes is that they remain ultimately unchanged by the reactions they catalyze. After an enzyme is done catalyzing a reaction, it releases its product(s). Figure 6.16 According to the induced-fit model, both enzyme and substrate undergo dynamic conformational changes upon binding. The enzyme contorts the substrate into its transition state, thereby increasing the rate of the reaction. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 263 Activity AP Biology Investigation 13: Enzyme Activity. This investigation allows you to design and conduct experiments to explore the effects of environmental variables, such as temperature and pH, on the rates of enzymatic reactions. Control of Metabolism Through Enzyme Regulation It would seem ideal to have a scenario in which all of the enzymes encoded in an organism’s genome existed in abundant supply and functioned optimally under all cellular conditions, in all cells, at all times. In reality, this is far from the case. A variety of mechanisms ensure that this does not happen. Cellular needs and conditions vary from cell to cell, and change within individual cells over time. The required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and functionality of different enzymes. Since the rates of biochemical reactions are controlled by activation energy, and enzymes lower and determine activation energies for chemical reactions, the relative amounts and functioning of the variety of enzymes within a cell ultimately determine which reactions will proceed and at which rates. This determination is tightly controlled. In certain cellular environments, enzyme activity is partly controlled by environmental factors, like pH and temperature. There are other mechanisms through which cells control the activity of enzymes and determine the rates at which various biochemical reactions will occur. Regulation of Enzymes by Molecules Enzymes can be regulated in ways that either promote or reduce their activity. There are many different kinds of molecules that inhibit or promote enzyme function, and various mechanisms exist for doing so. In some cases of enzyme inhibition, for example
, an inhibitor molecule is similar enough to a substrate that it can bind to the active site and simply block the substrate from binding. When this happens, the enzyme is inhibited through competitive inhibition, because an inhibitor molecule competes with the substrate for active site binding (Figure 6.17). On the other hand, in noncompetitive inhibition, an inhibitor molecule binds to the enzyme in a location other than an allosteric site and still manages to block substrate binding to the active site. Figure 6.17 Competitive and noncompetitive inhibition affect the rate of reaction differently. Competitive inhibitors affect the initial rate but do not affect the maximal rate, whereas noncompetitive inhibitors affect the maximal rate. Some inhibitor molecules bind to enzymes in a location where their binding induces a conformational change that reduces the affinity of the enzyme for its substrate. This type of inhibition is called allosteric inhibition (Figure 6.18). Most allosterically regulated enzymes are made up of more than one polypeptide, meaning that they have more than one protein subunit. When an allosteric inhibitor binds to an enzyme, all active sites on the protein subunits are changed slightly such that they bind their substrates with less efficiency. There are allosteric activators as well as inhibitors. Allosteric activators bind to locations on an enzyme away from the active site, inducing a conformational change that increases the affinity of 264 Chapter 6 \| Metabolism the enzyme’s active site(s) for its substrate(s). Figure 6.18 Allosteric inhibitors modify the active site of the enzyme so that substrate binding is reduced or prevented. In contrast, allosteric activators modify the active site of the enzyme so that the affinity for the substrate increases. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 265 Figure 6.19 Have you ever wondered how pharmaceutical drugs are developed? (credit: Deborah Austin) Drug Discovery by Looking for Inhibitors of Key Enzymes in Specific Pathways Enzymes are key components of metabolic pathways. Understanding how enzymes work and how they can be regulated is a key principle behind the development of many of the pharmaceutical drugs (Figure 6.19) on the market today. Biologists working in this field collaborate with other scientists, usually chemists, to design drugs. Consider statins for example—which is the name given to the class of drugs that reduces cholesterol levels. These compounds are essentially inhibitors
of the enzyme HMG-CoA reductase. HMG-CoA reductase is the enzyme that synthesizes cholesterol from lipids in the body. By inhibiting this enzyme, the levels of cholesterol synthesized in the body can be reduced. Similarly, acetaminophen is an inhibitor of the enzyme cyclooxygenase. While it is effective in providing relief from fever and inflammation (pain), its mechanism of action is still not completely understood. How are drugs developed? One of the first challenges in drug development is identifying the specific molecule that the drug is intended to target. In the case of statins, HMG-CoA reductase is the drug target. Drug targets are identified through painstaking research in the laboratory. Identifying the target alone is not sufficient; scientists also need to know how the target acts inside the cell and which reactions go awry in the case of disease. Once the target and the pathway are identified, then the actual process of drug design begins. During this stage, chemists and biologists work together to design and synthesize molecules that can either block or activate a particular reaction. However, this is only the beginning: both if and when a drug prototype is successful in performing its function, then it must undergo many tests from in vitro experiments to clinical trials before it can get FDA approval to be on the market. Statins reduce the level of cholesterol in the blood. Based on the everyday connection, which of the following might also reduce cholesterol levels in the blood? a. a drug that increases HMG-CoA reductase levels b. a drug that reduces cyclooxygenase levels c. a drug that reduces lipid levels in the body d. a drug that blocks the action of acetaminophen Many enzymes don’t work optimally, or even at all, unless bound to other specific non-protein helper molecules, either temporarily through ionic or hydrogen bonds or permanently through stronger covalent bonds. Two types of helper molecules are cofactors and coenzymes. Binding to these molecules promotes optimal conformation and function for their respective enzymes. Cofactors are inorganic ions such as iron (Fe++) and magnesium (Mg++). One example of an enzyme that requires a metal ion as a cofactor is the enzyme that builds DNA molecules, DNA polymerase, which requires a bound zinc ion (Zn++) to function. Coenzymes are organic helper molecules, with a basic atomic structure made up of carbon and 266 Chapter 6 \| Metabol
ism hydrogen, which are required for enzyme action. The most common sources of coenzymes are dietary vitamins (Figure 6.20). Some vitamins are precursors to coenzymes and others act directly as coenzymes. Vitamin C is a coenzyme for multiple enzymes that take part in building the important connective tissue component, collagen. An important step in the breakdown of glucose to yield energy is catalysis by a multi-enzyme complex called pyruvate dehydrogenase. Pyruvate dehydrogenase is a complex of several enzymes that actually requires one cofactor (a magnesium ion) and five different organic coenzymes to catalyze its specific chemical reaction. Therefore, enzyme function is, in part, regulated by an abundance of various cofactors and coenzymes, which are supplied primarily by the diets of most organisms. Figure 6.20 Vitamins are important coenzymes or precursors of coenzymes, and are required for enzymes to function properly. Multivitamin capsules usually contain mixtures of all the vitamins at different percentages. Enzyme Compartmentalization In eukaryotic cells, molecules such as enzymes are usually compartmentalized into different organelles. This allows for yet another level of regulation of enzyme activity. Enzymes required only for certain cellular processes can be housed separately along with their substrates, allowing for more efficient chemical reactions. Examples of this sort of enzyme regulation based on location and proximity include the enzymes involved in the latter stages of cellular respiration, which take place exclusively in the mitochondria, and the enzymes involved in the digestion of cellular debris and foreign materials, located within lysosomes. Feedback Inhibition in Metabolic Pathways Molecules can regulate enzyme function in many ways. A major question remains, however: What are these molecules and where do they come from? Some are cofactors and coenzymes, ions, and organic molecules, as you’ve learned. What other molecules in the cell provide enzymatic regulation, such as allosteric modulation, and competitive and noncompetitive inhibition? The answer is that a wide variety of molecules can perform these roles. Some of these molecules include pharmaceutical and non-pharmaceutical drugs, toxins, and poisons from the environment. Perhaps the most relevant sources of enzyme regulatory molecules, with respect to cellular metabolism, are the products of the cellular metabolic reactions themselves. In a most efficient and elegant way, cells have evolved to use the products of their own reactions for feedback inhibition
of enzyme activity. Feedback inhibition involves the use of a reaction product to regulate its own further production (Figure 6.21). The cell responds to the abundance of specific products by slowing down production during anabolic or catabolic reactions. Such reaction products may inhibit the enzymes that catalyzed their production through the mechanisms described above. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 267 Figure 6.21 Metabolic pathways are a series of reactions catalyzed by multiple enzymes. Feedback inhibition, where the end product of the pathway inhibits an upstream step, is an important regulatory mechanism in cells. The production of both amino acids and nucleotides is controlled through feedback inhibition. Additionally, ATP is an allosteric regulator of some of the enzymes involved in the catabolic breakdown of sugar, the process that produces ATP. In this way, when ATP is abundant, the cell can prevent its further production. Remember that ATP is an unstable molecule that can spontaneously dissociate into ADP. If too much ATP were present in a cell, much of it would go to waste. On the other hand, ADP serves as a positive allosteric regulator (an allosteric activator) for some of the same enzymes that are inhibited by ATP. Thus, when relative levels of ADP are high compared to ATP, the cell is triggered to produce more ATP through the catabolism of sugar. Section Summary Enzymes are chemical catalysts that accelerate chemical reactions at physiological temperatures by lowering their activation energy. Enzymes are usually proteins consisting of one or more polypeptide chains. Enzymes have an active site that provides a unique chemical environment, made up of certain amino acid R groups (residues). This unique environment is perfectly suited to convert particular chemical reactants for that enzyme, called substrates, into unstable intermediates called transition states. Enzymes and substrates are thought to bind with an induced fit, which means that enzymes undergo slight conformational adjustments upon substrate contact, leading to full, optimal binding. Enzymes bind to substrates and catalyze reactions in four different ways: bringing substrates together in an optimal orientation, compromising the bond structures of substrates so that bonds can be more easily broken, providing optimal environmental conditions for a reaction to occur, or participating directly in their chemical reaction by forming transient covalent bonds with the substrates. Enzyme action must be regulated so that in a given cell
at a given time, the desired reactions are being catalyzed and the undesired reactions are not. Enzymes are regulated by cellular conditions, such as temperature and pH. They are also regulated through their location within a cell, sometimes being compartmentalized so that they can only catalyze reactions under certain circumstances. Inhibition and activation of enzymes via other molecules are other important ways that enzymes are regulated. Inhibitors can act competitively, noncompetitively, or allosterically; noncompetitive inhibitors are usually allosteric. Activators can also enhance the function of enzymes allosterically. The most common method by which cells regulate the enzymes in metabolic pathways is through feedback inhibition. During feedback inhibition, the products of a metabolic pathway serve as inhibitors (usually allosteric) of one or more of the enzymes (usually the first committed enzyme of the pathway) involved in the pathway that produces them. 268 Chapter 6 \| Metabolism KEY TERMS activation energy energy necessary for reactions to occur active site specific region of the enzyme to which the substrate binds allosteric inhibition inhibition by a binding event at a site different from the active site, which induces a conformational change and reduces the affinity of the enzyme for its substrate anabolic (also, anabolism) pathways that require an input of energy to synthesize complex molecules from simpler ones ATP adenosine triphosphate, the cell’s energy currency bioenergetics study of energy flowing through living systems catabolic (also, catabolism) pathways in which complex molecules are broken down into simpler ones chemical energy potential energy in chemical bonds that is released when those bonds are broken coenzyme small organic molecule, such as a vitamin or its derivative, which is required to enhance the activity of an enzyme cofactor inorganic ion, such as iron and magnesium ions, required for optimal regulation of enzyme activity competitive inhibition type of inhibition in which the inhibitor competes with the substrate molecule by binding to the active site of the enzyme denature process that changes the natural properties of a substance endergonic describes chemical reactions that require energy input enthalpy total energy of a system entropy (S) measure of randomness or disorder within a system exergonic describes chemical reactions that release free energy feedback inhibition effect of a product of a reaction sequence to decrease its further production by inhibiting the activity of the first enzyme in the pathway that produces it free energy Gibbs free energy is the usable energy, or energy that is available to do work. heat energy energy transferred from one system to another
that is not work (energy of the motion of molecules or particles) heat energy total bond energy of reactants or products in a chemical reaction induced fit dynamic fit between the enzyme and its substrate, in which both components modify their structures to allow for ideal binding kinetic energy type of energy associated with objects or particles in motion metabolism all the chemical reactions that take place inside cells, including anabolism and catabolism phosphoanhydride bond bond that connects phosphates in an ATP molecule potential energy type of energy that has the potential to do work; stored energy substrate molecule on which the enzyme acts thermodynamics study of energy and energy transfer involving physical matter transition state high-energy, unstable state (an intermediate form between the substrate and the product) occurring during a chemical reaction This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 269 CHAPTER SUMMARY 6.1 Energy and Metabolism Cells perform the functions of life through various chemical reactions. A cell’s metabolism refers to the chemical reactions that take place within it. There are metabolic reactions that involve the breaking down of complex chemicals into simpler ones, such as the breakdown of large macromolecules. This process is referred to as catabolism, and such reactions are associated with a release of energy. On the other end of the spectrum, anabolism refers to metabolic processes that build complex molecules out of simpler ones, such as the synthesis of macromolecules. Anabolic processes require energy. Glucose synthesis and glucose breakdown are examples of anabolic and catabolic pathways, respectively. 6.2 Potential, Kinetic, Free, and Activation Energy Energy comes in many different forms. Objects in motion do physical work, and kinetic energy is the energy of objects in motion. Objects that are not in motion may have the potential to do work, and thus, have potential energy. Molecules also have potential energy because the breaking of molecular bonds has the potential to release energy. Living cells depend on the harvesting of potential energy from molecular bonds to perform work. Free energy is a measure of energy that is available to do work. The free energy of a system changes during energy transfers such as chemical reactions, and this change is referred to as ∆G. The ∆G of a reaction can be negative or positive, meaning that the reaction releases energy or consumes energy, respectively. A reaction with a negative ∆G that gives off energy is called an ex
ergonic reaction. One with a positive ∆G that requires energy input is called an endergonic reaction. Exergonic reactions are said to be spontaneous, because their products have less energy than their reactants. The products of endergonic reactions have a higher energy state than the reactants, and so these are nonspontaneous reactions. However, all reactions (including spontaneous –∆G reactions) require an initial input of energy in order to reach the transition state, at which they’ll proceed. This initial input of energy is called the activation energy. 6.3 The Laws of Thermodynamics In studying energy, scientists use the term “system” to refer to the matter and its environment involved in energy transfers. Everything outside of the system is called the surroundings. Single cells are biological systems. Systems can be thought of as having a certain amount of order. It takes energy to make a system more ordered. The more ordered a system is, the lower its entropy. Entropy is a measure of the disorder of a system. As a system becomes more disordered, the lower its energy and the higher its entropy become. A series of laws, called the laws of thermodynamics, describe the properties and processes of energy transfer. The first law states that the total amount of energy in the universe is constant. This means that energy can’t be created or destroyed, only transferred or transformed. The second law of thermodynamics states that every energy transfer involves some loss of energy in an unusable form, such as heat energy, resulting in a more disordered system. In other words, no energy transfer is completely efficient and tends toward disorder. 6.4 ATP: Adenosine Triphosphate ATP is the primary energy-supplying molecule for living cells. ATP is made up of a nucleotide, a five-carbon sugar, and three phosphate groups. The bonds that connect the phosphates (phosphoanhydride bonds) have high-energy content. The energy released from the hydrolysis of ATP into ADP + Pi is used to perform cellular work. Cells use ATP to perform work by coupling the exergonic reaction of ATP hydrolysis with endergonic reactions. ATP donates its phosphate group to another molecule via a process known as phosphorylation. The phosphorylated molecule is at a higher-energy state and is less stable than its unphosphorylated form, and this added energy from the addition of the phosphate allows the molecule to undergo its end
ergonic reaction. 6.5 Enzymes Enzymes are chemical catalysts that accelerate chemical reactions at physiological temperatures by lowering their activation energy. Enzymes are usually proteins consisting of one or more polypeptide chains. Enzymes have an active site that provides a unique chemical environment, made up of certain amino acid R groups (residues). This unique environment is perfectly suited to convert particular chemical reactants for that enzyme, called substrates, into unstable intermediates called transition states. Enzymes and substrates are thought to bind with an induced fit, which means that enzymes undergo slight conformational adjustments upon substrate contact, leading to full, optimal binding. Enzymes bind to substrates and catalyze reactions in four different ways: bringing substrates together in an optimal orientation, 270 Chapter 6 \| Metabolism compromising the bond structures of substrates so that bonds can be more easily broken, providing optimal environmental conditions for a reaction to occur, or participating directly in their chemical reaction by forming transient covalent bonds with the substrates. Enzyme action must be regulated so that in a given cell at a given time, the desired reactions are being catalyzed and the undesired reactions are not. Enzymes are regulated by cellular conditions, such as temperature and pH. They are also regulated through their location within a cell, sometimes being compartmentalized so that they can only catalyze reactions under certain circumstances. Inhibition and activation of enzymes via other molecules are other important ways that enzymes are regulated. Inhibitors can act competitively, noncompetitively, or allosterically; noncompetitive inhibitors are usually allosteric. Activators can also enhance the function of enzymes allosterically. The most common method by which cells regulate the enzymes in metabolic pathways is through feedback inhibition. During feedback inhibition, the products of a metabolic pathway serve as inhibitors (usually allosteric) of one or more of the enzymes (usually the first committed enzyme of the pathway) involved in the pathway that produces them. REVIEW QUESTIONS 1. Energy can be taken in as glucose, then has to be converted to a form that can be easily used to perform work in cells. What is the name of the latter molecule? a. anabolic molecules b. cholesterol c. electrolytes d. adenosine triphosphate 2. When cellular respiration occurs, what is the primary molecule used to store the energy that is released? a. AMP b. ATP c. mRNA d. phosphate 3. DNA replication involves
unwinding two strands of parent DNA, copying each strand to synthesize complementary strands and releasing the resulting two semi-conserved strands of DNA. Which of the following accurately describes this process? a. This is an anabolic process. b. This is a catabolic process. a. glucose b. protein c. d. triglycerides tRNA 6. What reaction will release the largest amount of energy to help power another reaction? a. AMP to ATP b. ATP to ADP c. DNA to proteins d. glucose to starch 7. Consider a pendulum swinging. Which type(s) of energy is/are associated with the pendulum in the following instances: 1. 2. 3. the moment at which it completes one cycle, just before it begins to fall back towards the other end the moment that it is in the middle between the two ends just before it reaches the end of one cycle (before step 1) a. 1. potential and kinetic c. This is both an anabolic and a catabolic process. 2. potential and kinetic d. This is a metabolic process, but is neither anabolic nor catabolic. 4. Which of the following is a catabolic process? a. digestion of sucrose b. dissolving sugar in water c. DNA replication d. RNA translation 5. What food molecule used by animals for energy and obtained from plants is most directly related to the use of sun energy? 3. kinetic b. 1. potential 2. potential and kinetic 3. potential and kinetic c. 1. potential 2. kinetic 3. potential and kinetic d. 1. potential and kinetic 2. kinetic 3. kinetic 8. Which of the following best describes energy? This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 271 the transfer of genetic information a. Both endergonic and exergonic reactions require a. b. c. d. the ability to assemble a large number of functional catalysts the ability to store solar output the ability to do work 9. What is the ultimate source of energy on this planet? a. glucose b. plants c. metabolic pathways d. the sun 10. Which of the following molecules is likely to have the most potential energy? a. ATP b. ADP c. glucose d. sucrose 11. Which of the following is the best way to judge the relative activation energies between two given chemical reactions? a. Compare the ΔG values
between the two reactions. b. Compare their reaction rates. c. Compare their ideal environmental conditions. d. Compare the spontaneity between the two reactions. 12. Which of the terms in the Gibbs free energy equation denotes enthalpy? a. ΔG b. ΔH c. ΔS d. ΔT 13. Which chemical reaction is more likely to occur? a. dehydration synthesis b. endergonic c. endothermic d. exergonic 14. Which of the following comparisons or contrasts between endergonic and exergonic reactions is false? a small amount of energy to overcome an activation barrier. b. Endergonic reactions have a positive ΔG and exergonic reactions have a negative ΔG. c. Endergonic reactions consume energy and exergonic reactions release energy. d. Endergonic reactions take place slowly and exergonic reactions take place quickly. 15. Label each of the following systems as high or low entropy: 1. perfume the instant after it is sprayed into the air 2. an unmaintained 1950s car compared with a brand new car 3. a living cell compared with a dead cell a. 1. low b. 2. high 3. 1. low low 2. high 3. high c. 1. high 2. low 3. high d. 1. high 2. 3. low low 16. What counteracts entropy? a. energy release b. endergonic reactions c. d. input of energy time 17. Which of the following is the best example of the first law of thermodynamics? a. a body getting warmer after exercise b. a piece of fruit spoiling in the fridge c. a power plant burning coal and producing electricity d. an exothermic chemical reaction 18. What is the difference between the first and second laws of thermodynamics? 272 Chapter 6 \| Metabolism a. The first law involves creating energy while the 24. An allosteric inhibitor does which of the following? second law involves expending it. b. The first law involves expending energy while the second involves creating it. a. binds to an enzyme away from the active site and changes the conformation of the active site, increasing its affinity for substrate binding c. The first law involves conserving energy while b. binds to an active site and blocks it from binding the second law involves the inability to recapture energy. d. The first law discusses creating energy while the second law discusses the energy requirement for reactions. 19. Which best describes
the effect of inputting energy into a living system? a. b. c. It decreases entropy within the system. It fuels catabolic reactions. It causes enthalpy. substrate c. binds to an enzyme away from the active site and changes the conformation of the active site, decreasing its affinity for the substrate d. binds directly to the active site and mimics the substrate 25. What happens if an enzyme is not functioning in a chemical reaction in a living organism that needs it? a. The reaction stops. b. The reaction proceeds, but much more slowly. d. The energy is used to produce carbohydrates. c. The reaction proceeds faster without the 20. Why is ATP considered the energy currency of the cell? interference. d. There is no change in the reaction rate. It accepts energy from chemical reactions. 26. Which of the following is not true about enzymes? a. They increase the ΔG of reactions. b. They are usually made of amino acids. c. They lower the activation energy of chemical reactions. d. Each one is specific to the particular substrate, or substrates, to which it binds. 27. Which of the following analogies best describe the induced-fit model of enzyme-substrate binding? a. a hug between two people b. a key fitting into a lock c. a square peg fitting through the square hole and a round peg fitting through the round hole of a children’s toy d. the fitting together of two jigsaw puzzle pieces 28. What is the function of enzymes? a. b. c. to increase the ΔG of reactions to increase the ΔH of reactions to lower the entropy of the chemicals in the reaction d. to lower the activation energy of a reaction a. b. c. d. It holds energy at the site of release from substrates. It is a protein. It can transport energy to locations within the cell. 21. What is ATP made from? a. adenosine + high energy electrons b. ADP + pyrophosphate c. AMP + ADP d. the conversion of guanine to adenosine 22. What is true about the energy released by the hydrolosis of ATP? a. It is equal to −57 kJ/mol. b. The cell harnesses it as heat energy in order to perform work. c. It is primarily stored between the alpha and beta phosphates. d. It provides energy to coupled reactions. 23. What part of ATP is broken
to release energy for use in chemical reactions? a. b. c. d. the adenosine molecule the bond between the first and second phosphates the bond between the first phosphate and the adenosine molecule the bond between the second and third phosphates This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 273 CRITICAL THINKING QUESTIONS 29. Describe the connection between anabolic and catabolic chemical reactions in a metabolic pathway. a. Catabolic reactions produce energy and simpler compounds, whereas anabolic reactions involve the use of energy to make more complex compounds. b. Catabolic reactions produce energy and complex compounds are formed, whereas in anabolic reactions free energy is utilized by complex compounds to make simpler molecules. c. Catabolic reactions utilize energy and gives simpler compounds, whereas in anabolic reactions reactions, energy is produced and simpler compounds are used to make complex molecules. d. Catabolic reactions produce energy and water molecules, whereas in anabolic reactions this free energy is utilized by simpler compounds to make only proteins and nucleic acids. 30. Does physical exercise involve anabolic processes, catabolic processes, or both? Give evidence for your answer. a. Physical exercise involves both catabolic and anabolic processes. Glucose is broken down into simpler compounds during physical activity. The simpler compounds are then used to provide energy to the muscles for contraction by the anabolic pathway. b. Physical exercise is just a catabolic process. Glucose is broken down into simpler compounds during physical activity and the simpler compounds are then used to provide energy to the muscles for contraction. c. Physical activity involves only anabolic processes. Glucose is broken down into simpler compounds during physical activity and the simpler compounds are then used to provide energy to the muscles for contraction by anabolic pathways. d. Physical exercise involves both anabolic and catabolic processes. Cellulose is broken down into simpler compounds during physical activity. The simpler compounds are then used to provide energy to the muscles for contraction by anabolic pathways. 31. How do chemical reactions play a role in energy transfer? a. Energy from the breakdown of glucose and other molecules in animals is released as ATP, which transfer energy to other reactions. b. Energy from the breakdown of glucose and other molecules in animals is released in the form of NADP, which transfers energy to other reactions. c. Energy is released in the form of glucose from the breakdown of ATP
molecules. These ATP molecules transfer energy from one reaction to other. d. Energy is released in the form of water from the breakdown of glucose. These molecules transfer energy from one reaction to other. 32. Name two different cellular functions that require energy. a. Phagocytosis helps amoebae take up nutrients and pseudopodia help the amoebae move. b. Phagocytosis allows amoebae to move and pseudopodia help in the uptake of nutrients. c. Phagocytosis helps amoebae to take up nutrients and cilia help amoebae move. d. Phagocytosis helps amoebae in cell division and pseudopodia help amoebae move. 33. Explain the conversion of energy that takes place when the sluice of a dam is opened. a. Potential energy stored in the water held by the dam will convert to kinetic energy when it falls through the opening of the sluice. b. Kinetic energy stored in the water held by the dam will convert to potential energy when it falls through the opening of the sluice. c. Potential energy stored in the water held by the dam will convert to electrical energy, when it falls through the opening of the sluice. d. Hydrothermal energy stored in the water held by the dam will convert to kinetic energy, when it falls through the opening of the sluice. 34. Explain in your own words the difference between a spontaneous reaction and one that occurs instantaneously. 274 Chapter 6 \| Metabolism a. A spontaneous reaction is one which releases free energy and moves to a more stable state. Instantaneous reactions occur rapidly with sudden release of energy. b. A spontaneous reaction is one which utilizes free energy and moves to a more stable state. Instantaneous reactions occur rapidly with sudden release of energy. c. A spontaneous reaction is one which releases free energy and moves to a more stable state. Instantaneous reactions occur rapidly within a system by uptake of energy. d. A spontaneous reaction is one in which the reaction occurs rapidly with sudden release of energy. Instantaneous reaction releases free energy and moves to a more stable state. a. The ant farm is in the state of high entropy after the earthquake and energy must be spent to bring the system to low entropy. b. The ant farm is in the state of lower entropy after the earthquake and energy must be spent to bring the system to high entropy. c. The ant
farm is in the state of higher entropy before the earthquake and energy is given out of the system after the earthquake. d. The ant farm is in the state of lower entropy before the earthquake and energy is given out of the system after the earthquake. 37. Energy transfers take place constantly in every day activities. Think of two scenarios: cooking on a stove and driving. Explain how the second law of thermodynamics applies to these scenarios. 35. Describe the position of the transition state on a vertical energy scale, from low to high, relative to the position of the reactants and products, for both endergonic and exergonic reactions. a. The transition state of the reaction exists at a lower energy level than the reactants. Activation energy is always positive regardless of whether the reaction is exergonic or endergonic. b. The transition state of the reaction exists at a higher energy level than the reactants. Activation energy is always positive regardless of whether the reaction is exergonic or endergonic. c. The transition state of the reaction exists at a lower energy level than the reactants. Activation energy is always negative regardless of whether the reaction is exergonic or endergonic. d. The transition state of the reaction exists at an intermediate energy level than that of the reactants. Activation energy is always positive regardless of whether the reaction is exergonic or endergonic. 36. Imagine an elaborate ant farm with tunnels and passageways through the sand where ants live in a large community. Now imagine that an earthquake shook the ground and demolished the ant farm. In which of these two scenarios, before or after the earthquake, was the ant farm system in a state of higher or lower entropy? Why? a. Heat is lost into the room while cooking and into the metal of the engine during gasoline combustion. b. Heat gained while cooking helps to make the food and heat released due to gasoline combustion helps the car accelerate. c. The energy given to the system remains constant during cooking and more energy is added to the car engine when the gasoline combusts. d. The energy given to the system for cooking helps to make food and energy in the car engine remains conserved when gasoline combustion takes place. 38. What does it mean for a system to be in a higher level of entropy? How can it be reduced? a. Higher level of entropy refers to higher state of disorder in the system and it can be reduced by input of energy to lower the entropy. b. Higher
level of entropy refers to higher state of symmetry in the system and it can be reduced by release of energy to lower the entropy. c. Higher level of entropy refers to low disorder in the system and it can be reduced by input of energy to increase the entropy. d. Higher level of entropy refers to higher state of disorder in the system and it can be reduced by providing a catalyst to lower the entropy. 39. When the air temperature drops and rain turns to snow, which law of thermodynamics is exhibited? a. b. c. first law of thermodynamics second law of thermodynamics third law of thermodynamics d. zeroth law of thermodynamics 40. How does ATP supply energy to chemical reactions? This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 275 a. ATP dissociates and the energy released by breaking of a phosphate bond within ATP is used for phosphorylation of another molecule. ATP hydrolysis also provides energy to power coupling reactions. b. ATP utilizes energy to power exergonic reactions by hydrolysis of ATP molecule. The free energy released as a result of ATP breakdown is used to carry out metabolism of products. c. ATP utilizes energy to power endergonic reactions by dehydration of ATP molecule. The free energy released as a result of ATP breakdown is used to carry out metabolism of products. d. ATP utilizes the energy released from the coupling reactions and that energy is used to power the endergonic and exergonic reactions. 41. Is the EA Explain your reasoning. for ATP hydrolysis relatively low or high? a. EA for ATP hydrolysis is high because considerable energy is released. b. EA for ATP hydrolysis is low because considerable energy is released. c. EA for ATP hydrolysis is intermediate because considerable energy is released. d. EA for ATP hydrolysis is high because a low amount of energy is released. 42. What is phosphorylation as it occurs in chemical reactions? a. Phosphorylation refers to the attachment of a phosphate to another molecule to facilitate a chemical reaction. b. Phosphorylation is the uptake of a phosphorous molecule by an ATP molecule to power chemical reactions. c. Phosphorylation is the release of a third phosphorous molecule of ATP during hydrolysis. d. Phosphorylation is the breakdown of a pyrophosphate molecule which gives phosphate ions.
TEST PREP FOR AP® COURSES 46. Cell metabolism is a complex process that uses many types of chemicals in a variety of processes. Which of the following statements is true? 43. If a chemical reaction could occur without an enzyme, why is it important to have one? a. Enzymes are important because they give the desired products only from the reaction. b. Enzymes are important because the products are obtained consistently with time. c. Enzymes are important because it does not disturb the concentration of the products. d. Enzymes are important because energy remains conserved and no loss of energy occurs. 44. How does enzyme feedback inhibition benefit a cell? a. Feedback inhibition benefits the cell by blocking the production of the products by changing the configuration of enzymes. This will prevent the cells from becoming toxic. b. Feedback inhibition benefits the cell by blocking the production of the reactants by changing the configuration of enzymes. This will prevent the cells from becoming toxic. c. Feedback inhibition benefits the cell by blocking the production of the products by changing the configuration of reactants. This will prevent the cells from becoming toxic. d. Feedback inhibition benefits the cell by blocking the production of the products by reducing the reactants. This will prevent the cells from becoming toxic. 45. What type of reaction allows chemicals to be available for an organism’s growth and maintenance in a timely manner? a. enzymatically facilitated reactions b. redox reactions c. catabolic reactions d. hydrolysis of ATP a. A loss of free nucleotides would result in cancer. b. A loss of assorted carbohydrates would result in mitosis. c. A loss of triglycerides would result in cell death. d. A loss of enzymes would result in cell death. 47. Which pair of descriptors of chemical reactions go Chapter 6 \| Metabolism a. Anabolic pathways involve the breakdown of nutrient molecules into usable forms. An example is the harvesting of amino acids from dietary proteins. b. Anabolic pathways involve the breakdown of nutrient molecules into useable forms. An example is the use of glycogen by the liver to maintain blood glucose levels. c. Anabolic pathways build new molecules out of the products of catabolic pathways. An example is the separation of fatty acids from triglycerides to satisfy energy needs. d. Anabolic pathways build new molecules out of the products of catabolic pathways. An example is the linkage of nucleotides to form a molecule of mRNA. 52. If glucose is broken
down through aerobic respiration, a number of ATP can be made from the energy extracted. How many ATP are possible? a. 2 to 4 b. 36 to 38 c. 10 to 12 d. 24 to 30 53. Plants must have adequate resources to complete their functions. If they do not have what they need, there are changes in the organism’s metabolism. What happens to the metabolism of a plant that does not have adequate sunlight? a. Photosynthesis slows and less glucose is produced for energy use. b. The plant switches to anaerobic metabolism. c. The plant goes into a dormant state until the sunlight returns. d. The plant flowers quickly to reproduce while it can. 54. Water deficiency is arguably the easiest deficiency to detect in plants. This is because plants that are lacking water will wilt, as water within the plant’s cells helps to supports the plant’s weight. Plant cells become water deficient because their cells use the water for metabolic processes. What happens to the metabolism of a plant that does not have adequate water? 276 together? a. anabolic and exergonic b. exergonic and dehydration synthesis c. endergonic and catabolic d. hydrolysis and exergonic 48. What is the underlying principle that supports the idea that all living organisms share the same core processes and features? a. All organisms must harvest energy from their environment and convert it to ATP to carry out cellular functions. b. Plants produce their own energy and pass it on to animals. c. Herbivores, carnivores, and omnivores coexist for the survival of all. d. Glucose is the primary source of energy for all cellular functions. 49. It has been accepted that life on the Earth started out as single celled, simple organisms, which then evolved into complex organisms. How did evolution proceed to produce such a wide variety of living organisms from a simple ancestor? a. Prokaryotes produced the fungi, then the protists which then branches to plants and animals. b. Protists evolved first, then the prokaryotes, which branched into the fungi, plants, and animals c. Prokaryotes produced the protists, which branched into the fungi, plants, and animals. d. Prokaryotes produced the protists, then the fungi, which branched into the plants and animals. 50. Plants make glucose through a pathway called photosynthesis. The amount of energy captured from light can
be expressed as the number of energy containing molecules used to make one molecule of glucose. Which of the following best states the number of each molecule needed? a. 54 molecules of ATP and 18 molecules of nicotinamide adenine dinucleotide phosphate (NADPH) b. 18 molecules of ATP and 12 molecules of NADPH c. 24 molecules of ATP and 18 molecules of NADPH d. 12 molecules of ATP and 18 molecules of NADPH 51. What is an anabolic pathway? Which of these is an example of an anabolic pathway used by cells in their metabolism? This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 277 a. Photosynthesis is inhibited, less glucose is produced, and water used by the cells is not replaced. a. Both enzyme and substrate undergo dynamic changes, inducing the transitions state of the substrate. b. The plant increases its breakdown of glucose to create more water at the end of the process. b. The enzyme induces a change in the substrate, but is not changed itself during the reaction. c. The plant will stop photosynthesizing for long periods of time until it has enough water to do so. d. The cell will bring in more CO2, to compensate for the lack of water, allowing glucose synthesis to continue. 55. Enzymes facilitate chemical reactions that result in changes to a substrate. How does the induced fit model of enzymes and substrates explain their function? c. The substrates attach to the enzyme and the chemical reaction proceeds. d. The enzyme changes shape to fit the substrate causing the transition state to occur. 56. Enzyme inhibitors play an important part in the control of enzyme functions, allowing them to continue, or inhibiting them for a period of time. Which inhibitor affects the initial rate but do not affect the maximal rate? a. allosteric b. competitive c. non-competitive d. uncompetitive SCIENCE PRACTICE CHALLENGE QUESTIONS 57. Activation energy is required for a reaction to proceed, and it is lower if the reaction is catalyzed. Sucrose (table sugar) is a disaccharide. When we eat sucrose it is converted to carbon dioxide and water, as with other carbohydrates. 1. Identify if the breakdown of sucrose is endergonic or exergonic. Explain the reasoning for your identification. 2. Based on your identification, explain if cubes of sugar
can be stored in a sugar bowl by creating a diagram similar to Figure 6.10. 3. 4. 5. If table sugar is placed in a spoon held over a high flame, the sugar is charred and becomes a blackened mixture composed primarily of carbon. Create a visual representation that includes a chemical equation to explain the role of the flame in this process. In terms of your answers to questions 1-3, predict if sugar cubes in a bowl placed in a dish of water can be stored on a table, and justify your prediction. [Extension] The energy of activation of a chemical reaction can be determined by measurement of the effect of temperature on reaction rate. The natural logarithm of the reaction rate constant is a linear function of the inverse of the temperature in Kelvin degrees. The negative of the slope of that graph is the energy of activation divided by the universal ideal gas constant, R = 8.314 J/Kmol. Using the following data (R. Wolfenden and Yang Yean, Journal of the American Chemical Society, 2008 Jun 18; 130(24): 7,548–7,549) evaluate the energy of activation of the following reaction. sucrose → fructose + glucose 278 Chapter 6 \| Metabolism 1. For each process, identify if it is endergonic or exergonic, and provide reasoning for your identification that includes your definition of the system. 2. For each process, does entropy increase or decrease? Explain your reasoning in terms of changes in the amount of order within the system. 3. For each process, is there an input of energy? Explain your reasoning in terms of (a) the source of the energy input into the system and (b) the interaction between the system and its environment that provides that input of energy. 61. Energy transfers occur constantly in daily activities. Think of two scenarios: cooking on a stove and driving a car. For each scenario, describe the system and explain how the second law of thermodynamics applies to the system in terms of energy input and change in entropy. 62. Consider a simple process that illustrates the change in entropy when energy is transferred. Temperature (K) ln(rate) 440 423 403 388 Table 6.1 -3.8 -4.5 -5 -6 (a) Construct a graph of ln(rate) versus 1/T(K) and determine the energy of activation for the uncatalyzed reaction. (b) Based on the data, explain the importance of enzymes for time
scales characteristic of living systems on Earth—that is to say, life as we know it. The time scale required for half of the molecules of initial sucrose to remain can be estimated. The relationship between the half-life and the activation energy is: t1 / 2 = 0.69×10 E A / 2.3RT At a temperature of 300K, approximately room temperature, RT is equal to 2,494 J/mole. 58. Physical exercise involves both anabolic and catabolic processes. For each process, explain an expected outcome and describe an example of a specific exercise that can lead to the expected outcome. 59. Explanations in science are often constructed by analogy. Explanations of the behavior of a poorly understood phenomenon can often be constructed by analogy to a phenomenon that is well understood. For each of the following cellular functions that require free energy, describe a parallel human activity and identify a source of free energy for that activity. For example, the synthesis of proteins can be expected to proceed as an assembly of a small set of sub-components, just as the construction of a building is accomplished by gathering and joining materials. It is consistent with our analogy to expect that there must be a free-energy resource that is consumed in the synthesis of proteins, just as hydrocarbon fuels are a source of energy for the construction of a building. 60. Look at each of the processes shown in Figure 6.8 that show examples of endergonic and exergonic processes. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 6 \| Metabolism 279 1. Take a block of ice as a system with a gasoline in an internal combustion engine? temperature of 0°C. This is water as a solid, so it has a high structural order. This means that the molecules are in a fixed position. As a result, the entropy of the system is low. 2. Allow the ice to melt at room temperature. Describe changes in the motion and interactions of water molecules before and after melting. Explain where the energy came from whose transfer produced melting. Predict the effect of the energy transfer on the entropy on the system, and justify your prediction. 3. Heat the water until the temperature reaches boiling point. Explain what happens to the entropy of the system when the water is heated. 4. Continue to heat the water at the constant temperature of the boiling point. Describe changes in the motion and interactions of water molecules before
and after boiling. Predict the effect of the energy transfer on the entropy of the system, and justify your prediction. 5. [Extension/Connection] Molecules of water have simple responses to heating: The molecules move faster and interact less strongly with other neighboring molecules. Consider the primary producers of an aquatic ecosystem in summer. Describe the source of energy transfer to the system of photosynthetic plants and algae. Predict changes in the system in response. Explain what happens to the entropy of this trophic level when energy transfer occurs. Now consider the primary producers and their aqueous environment as the system. Explain what happens to the entropy of this system composed of photosynthetic organisms and their abiotic environment. 6. Predict the change in entropy of the system when both autotrophs and their abiotic environment are considered. Justify your prediction. Predict the signs of the entropy changes in both biotic and abiotic components of this system. Predict the relative magnitudes of these entropy changes, and justify your prediction. 63. The sodium-potassium pump is an example of freeenergy coupling. The free energy derived from exergonic ATP hydrolysis is used to pump sodium and potassium ions across the cell membrane. The hydrolysis of one ATP molecule releases 7.3 kcal/mol of free energy (ΔG = -7.3 kcal/mol). If it takes 2.1 kcal/mol of free energy to move one Na+ across the membrane (ΔG = +2.1 kcal/mol), how many sodium ions could be moved by the hydrolysis of one ATP molecule? Show your calculations to provide reasoning for your answer. 64. Is the EA for ATP hydrolysis in cells likely relatively low or high compared to the EA for the combustion of 1. Explain your reasoning in terms of the relative stabilities of ATP and gasoline compared to air in which no catalysts are present. 2. Describe how the role of the enzyme ATPase in the hydrolysis of ATP in a cell differs from a spark in the cylinder of an internal combustion engine. 3. Describe a strategy for collecting data that can be used to measure the energies of activation (EA) of each of these two processes with instruments that can measure concentrations of reactions produced in each system. 65. Vitamin B12 is a co-enzyme involved in a wide variety of cellular processes. Synthesis of vitamin B12 occurs only in bacteria; in animals, these bacteria populate anaerobic environments in the gut
. Consequently, vegan diets in developing nations and diets common to developing nations provide no source of B12. Researchers (Ghosh et al. http://dx.doi.org/10.3389/fnut.2016.00001]) found that rats whose diets contained limited (L) and no (N) B12 displayed symptoms that were not observed in the control group (C) whose diet included B12 and was otherwise identical. Chemical analysis of adipocytokines in the plasma after feeding periods of 4 and 12 weeks are shown in the following table. Adipocytokines Tissue of origin Feeding duration (weeks) Leptin (pg/L) Adipose MCP-1 (mg/L) Monocytes IL-6 (mg/L) Monocytes Table 6.2 4 12 4 12 4 12 C L N 5.7± 0.21 5.8± 0.39 5.8± 0.25 6.5± 0.36 6.1± 0.25 9.9± 0.68 43.0± 1.18 44.4± 1.95 46.9± 2.08 43.2± 2.47 45.3± 3.02 49.5± 1.27 150± 3.2 151± 6.7 154± 4.5 176± 11.0 184± 8.0 185± 8.2 The sample size for these data are small: n = 6, within each group. Also shown in the table are cells in which these cytokine messages originate. Adipose cells store fats. Monocytes are white blood cells of the immune system. Over the 12 weeks of feeding, the weights of all three groups were equivalent, while the percent of body fat increased relative to the control for the rats fed a diet of 280 Chapter 6 \| Metabolism limited and no B12: 40% (N) and 20% (L), respectively. a. b. c. Identify which adipocytokines show significant increases, relative to the control group, after only 4 weeks of treatment. Justify your identification. Identify which adipocytokines show only significant increases, relative to the control group, after 12 weeks of treatment. Justify your identification. Identify which adipocytokines show significant increases, relative to the control group, after 4 weeks of treatment but no further increase after 12 weeks. Justify your identification. Adipocytokines are chemical mess
engers that regulate metabolism and blood vessel production and dilation. High concentrations of adipocytokines are commonly found among individuals with abnormal autoimmune response. Monocyte chemoattractant protein 1 (MCP-1) is involved in the trafficking or guiding of monocytes to damaged tissue, as in a wound. In mice, leptin receptors of cells in the hypothalamus suppress hunger. Interleukin (IL-6) is released to initiate and then regulate inflammation in response to an infection. The mice in this study were not infected or wounded. d. Construct an explanation, with reasoning based on the evidence provided by these data, for the observed variations in adipocytokines. Many noncommunicable diseases are associated with abnormal autoimmune responses, and the number of diseases that involve abnormal autoimmune response is increasing. Many autoimmune diseases, such as diabetes and heart disease, occur in developed nations at a much higher frequency than in developing nations. e. Evaluate, based on these data concerning the effect of restrictions on the availability of B12, the following question: Does the increased lack of exposure to pathogens in developed nations lead to reduced or abnormal immune response? 66. Using an example, explain how enzyme feedback inhibition regulation regulates a cellular process. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 281 7 \| CELLULAR RESPIRATION Figure 7.1 This geothermal energy plant transforms thermal energy from deep in the ground into electrical energy, which can be easily used. (credit: modification of work by the U.S. Department of Defense) Chapter Outline 7.1: Energy in Living Systems 7.2: Glycolysis 7.3: Oxidation of Pyruvate and the Citric Acid Cycle 7.4: Oxidative Phosphorylation 7.5: Metabolism without Oxygen 7.6: Connections of Carbohydrate, Protein, and Lipid Metabolic Pathways 7.7: Regulation of Cellular Respiration Introduction The electrical energy plant in Figure 7.1 converts energy from one form to another form that can be more easily used. This type of generating plant starts with underground thermal energy (heat) and transforms it into electrical energy that will be transported to homes and factories. Like a generating plant, plants and animals also must take in energy from the environment and convert it into a form that their cells can use. Energy enters an organism’s body in
one form and is converted into another form that can fuel the organism’s life functions. In the process of photosynthesis, plants and other photosynthetic producers take in energy in the form of light (solar energy) and convert it into chemical energy, glucose, which stores this energy in its chemical bonds. Then, a series of metabolic pathways, collectively called cellular respiration, extract the energy from the carbon–carbon bonds of glucose and convert it into a form that all living things can use—both producers, such as plants, and consumers, such as animals. Nearly all organisms perform glycolysis, the first part of both aerobic and anaerobic respiration. One of the key enzymes of glycolysis is pyruvate kinase. Without this enzyme, an organism will die because it is unable to convert nutrients into the energy it needs for survival. Scientists have taken advantage of that fact by blocking pyruvate kinase in some deadly parasites, such as the ones that cause African Sleeping Sickness and Chagas disease. Read more about this research here (http://openstaxcollege.org/l/32africa). 282 Chapter 7 \| Cellular Respiration 7.1 \| Energy in Living Systems In this section, you will explore the following questions: • What is the importance of electrons for the transfer of energy in living systems? • How is ATP used by the cell as an energy source? Connection for AP® Courses As we learned in previous chapters, living organisms require free energy to power life processes such as growth, reproduction, movement, and active transport. ATP (adenosine triphosphate) functions as the energy currency for cells. It allows the cells to store energy and transfer it within the cells to provide energy for cellular processes such as growth, movement and active transport. The ATP molecule consists of a ribose sugar and an adenine base with three phosphates attached. In the hydrolysis of ATP, free energy is supplied when a phosphate group or two are detached, and either ADP (adenosine diphosphate) or AMP (adenosine monophosphate) is produced. Energy derived from the metabolism of glucose is used to convert ADP to ATP during cellular respiration. As we explore cellular respiration, we’ll learn that the two ways ATP is regenerated by the cell are called substrate-level phosphorylation and oxidative phosphorylation. Information presented and the examples highlighted in the section support
concepts and Learning Objectives outlined in Big Idea 2 and Big Idea 4 of the AP® Biology Curriculum Framework, as shown in the table. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices. Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Science Practice Learning Objective Essential Knowledge Science Practice Learning Objective Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and maintenance of living systems require free energy and matter. 2.A.2 Organisms capture and store free energy for use in biological processes. 1.4 The student can use representations and models to analyze situations or solve problems qualitatively and quantitatively. 3.1 The student can pose scientific questions. 2.4 The student is able to use representations to pose scientific questions about what mechanisms and structural features allow organisms to capture, store, and use free energy. 2.A.2 Organisms capture and store free energy for use in biological processes. 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.5 The student is able to construct explanations of the mechanisms and structural features of cells that allow organisms to capture, store, or use free energy. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.5][APLO 2.16] Energy production within a cell involves many coordinated chemical pathways. Most of these pathways are combinations of oxidation and reduction reactions. Oxidation and reduction occur in tandem. An oxidation reaction strips an electron from an atom in a compound, and the addition of this electron to another compound is a reduction reaction. Because oxidation This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 283 and reduction usually occur together, these pairs of reactions are called oxidation reduction reactions, or redox reactions. Electrons and Energy The removal of an electron from a molecule, oxidizing it, results in a decrease in potential energy in the oxidized compound. The electron (sometimes as part of a hydrogen atom), does not remain unbonded, however, in the cytoplasm of a cell.
Rather, the electron is shifted to a second compound, reducing the second compound. The shift of an electron from one compound to another removes some potential energy from the first compound (the oxidized compound) and increases the potential energy of the second compound (the reduced compound). The transfer of electrons between molecules is important because most of the energy stored in atoms and used to fuel cell functions is in the form of high-energy electrons. The transfer of energy in the form of electrons allows the cell to transfer and use energy in an incremental fashion—in small packages rather than in a single, destructive burst. This chapter focuses on the extraction of energy from food; you will see that as you track the path of the transfers, you are tracking the path of electrons moving through metabolic pathways. Electron Carriers In living systems, a small class of compounds functions as electron shuttles: They bind and carry high-energy electrons between compounds in pathways. The principal electron carriers we will consider are derived from the B vitamin group and are derivatives of nucleotides. These compounds can be easily reduced (that is, they accept electrons) or oxidized (they lose electrons). Nicotinamide adenine dinucleotide (NAD) (Figure 7.2) is derived from vitamin B3, niacin. NAD+ is the oxidized form of the molecule; NADH is the reduced form of the molecule after it has accepted two electrons and a proton (which together are the equivalent of a hydrogen atom with an extra electron). NAD+ can accept electrons from an organic molecule according to the general equation: RH Reducing agent + NAD+ Oxidizing agent → NADH Reduced + R Oxidized When electrons are added to a compound, they are reduced. A compound that reduces another is called a reducing agent. In the above equation, RH is a reducing agent, and NAD+ is reduced to NADH. When electrons are removed from compound, it is oxidized. A compound that oxidizes another is called an oxidizing agent. In the above equation, NAD+ is an oxidizing agent, and RH is oxidized to R. Similarly, flavin adenine dinucleotide (FAD+) is derived from vitamin B2, also called riboflavin. Its reduced form is FADH2. A second variation of NAD, NADP, contains an extra phosphate group. Both NAD+ and FAD+ are extensively used in energy extraction from sugars, and NADP plays an important role in anabolic reactions
and photosynthesis. Figure 7.2 The oxidized form of the electron carrier (NAD+) is shown on the left and the reduced form (NADH) is shown on the right. The nitrogenous base in NADH has one more hydrogen ion and two more electrons than in NAD+. 284 Chapter 7 \| Cellular Respiration ATP in Living Systems A living cell cannot store significant amounts of free energy. Excess free energy would result in an increase of heat in the cell, which would result in excessive thermal motion that could damage and then destroy the cell. Rather, a cell must be able to handle that energy in a way that enables the cell to store energy safely and release it for use only as needed. Living cells accomplish this by using the compound adenosine triphosphate (ATP). ATP is often called the “energy currency” of the cell, and, like currency, this versatile compound can be used to fill any energy need of the cell. How? It functions similarly to a rechargeable battery. When ATP is broken down, usually by the removal of its terminal phosphate group, energy is released. The energy is used to do work by the cell, usually by the released phosphate binding to another molecule, activating it. For example, in the mechanical work of muscle contraction, ATP supplies the energy to move the contractile muscle proteins. Recall the active transport work of the sodium-potassium pump in cell membranes. ATP alters the structure of the integral protein that functions as the pump, changing its affinity for sodium and potassium. In this way, the cell performs work, pumping ions against their electrochemical gradients. ATP Structure and Function At the heart of ATP is a molecule of adenosine monophosphate (AMP), which is composed of an adenine molecule bonded to a ribose molecule and to a single phosphate group (Figure 7.3). The addition of a second phosphate group to this core molecule results in the formation of adenosine diphosphate (ADP); the addition of a third phosphate group forms adenosine triphosphate (ATP). Figure 7.3 ATP (adenosine triphosphate) has three phosphate groups that can be removed by hydrolysis to form ADP (adenosine diphosphate) or AMP (adenosine monophosphate).The negative charges on the phosphate group naturally repel each other, requiring energy to bond them together and releasing energy when these bonds are broken. The addition of a
phosphate group to a molecule requires energy. Phosphate groups are negatively charged and thus repel one another when they are arranged in series, as they are in ADP and ATP. This repulsion makes the ADP and ATP molecules inherently unstable. The release of one or two phosphate groups from ATP, a process called dephosphorylation, releases energy. Energy from ATP Hydrolysis is the process of breaking complex macromolecules apart. During hydrolysis, water is split, or lysed, and the resulting hydrogen atom (H+) and a hydroxyl group (OH-) are added to the larger molecule. The hydrolysis of ATP produces ADP, together with an inorganic phosphate ion (Pi), and the release of free energy. To carry out life processes, ATP is continuously broken down into ADP, and like a rechargeable battery, ADP is continuously regenerated into ATP by the reattachment of a third phosphate group. Water, which was broken down into its hydrogen atom and hydroxyl group during ATP hydrolysis, is regenerated when a third phosphate is added to the ADP molecule, reforming ATP. Obviously, energy must be infused into the system to regenerate ATP. Where does this energy come from? In nearly every living thing on earth, the energy comes from the metabolism of glucose. In this way, ATP is a direct link between the limited set of exergonic pathways of glucose catabolism and the multitude of endergonic pathways that power living cells. Phosphorylation Recall that, in some chemical reactions, enzymes may bind to several substrates that react with each other on the enzyme, This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 285 forming an intermediate complex. An intermediate complex is a temporary structure, and it allows one of the substrates (such as ATP) and reactants to more readily react with each other; in reactions involving ATP, ATP is one of the substrates and ADP is a product. During an endergonic chemical reaction, ATP forms an intermediate complex with the substrate and enzyme in the reaction. This intermediate complex allows the ATP to transfer its third phosphate group, with its energy, to the substrate, a process called phosphorylation. Phosphorylation refers to the addition of the phosphate (~P). This is illustrated by the following generic reaction: A + enzyme + ATP → ⎡ �
�A − enzyme − ∼ P⎤ ⎦ → B + enzyme + ADP + phosphate ion When the intermediate complex breaks apart, the energy is used to modify the substrate and convert it into a product of the reaction. The ADP molecule and a free phosphate ion are released into the medium and are available for recycling through cell metabolism. Substrate Phosphorylation ATP is generated through two mechanisms during the breakdown of glucose. A few ATP molecules are generated (that is, regenerated from ADP) as a direct result of the chemical reactions that occur in the catabolic pathways. A phosphate group is removed from an intermediate reactant in the pathway, and the free energy of the reaction is used to add the third phosphate to an available ADP molecule, producing ATP (Figure 7.4). This very direct method of phosphorylation is called substrate-level phosphorylation. Figure 7.4 In phosphorylation reactions, the gamma phosphate of ATP is attached to a protein. Oxidative Phosphorylation Most of the ATP generated during glucose catabolism, however, is derived from a much more complex process, chemiosmosis, which takes place in mitochondria (Figure 7.5) within a eukaryotic cell or the plasma membrane of a prokaryotic cell. Chemiosmosis, a process of ATP production in cellular metabolism, is used to generate 90 percent of the ATP made during glucose catabolism and is also the method used in the light reactions of photosynthesis to harness the energy of sunlight. The production of ATP using the process of chemiosmosis is called oxidative phosphorylation because of the involvement of oxygen in the process. Figure 7.5 In eukaryotes, oxidative phosphorylation takes place in mitochondria. In prokaryotes, this process takes place in the plasma membrane. (Credit: modification of work by Mariana Ruiz Villareal) 286 Chapter 7 \| Cellular Respiration Think About It Explain why it is more metabolically efficient for cells to extract energy from ATP rather than from the bonds of carbohydrates directly. Mitochondrial Disease Physician What happens when the critical reactions of cellular respiration do not proceed correctly? Mitochondrial diseases are genetic disorders of metabolism. Mitochondrial disorders can arise from mutations in nuclear or mitochondrial DNA, and they result in the production of less energy than is normal in body cells. In type 2 diabetes, for instance, the oxidation efficiency of NADH is reduced, impacting oxidative phosphorylation
but not the other steps of respiration. Symptoms of mitochondrial diseases can include muscle weakness, lack of coordination, stroke-like episodes, and loss of vision and hearing. Most affected people are diagnosed in childhood, although there are some adult-onset diseases. Identifying and treating mitochondrial disorders is a specialized medical field. The educational preparation for this profession requires a college education, followed by medical school with a specialization in medical genetics. Medical geneticists can be board certified by the American Board of Medical Genetics and go on to become associated with professional organizations devoted to the study of mitochondrial diseases, such as the Mitochondrial Medicine Society and the Society for Inherited Metabolic Disease. 7.2 \| Glycolysis In this section, you will explore the following question: • What is the overall result, in terms of molecules produced, in the breakdown of glucose by glycolysis? Connection for AP® Courses All organisms, from simple bacteria and yeast to complex plants and animals, carry out some form of cellular respiration to capture and supply free energy for cellular processes. Although cellular respiration and photosynthesis evolved as independent processes, today they are interdependent. The products of photosynthesis, carbohydrates and oxygen gas, are used during cellular respiration. Likewise, the byproduct of cellular respiration, CO2 gas, is used during photosynthesis. Glycolysis is the first pathway used in the breakdown of glucose to extract free energy. Used by nearly all organisms on earth today, glycolysis likely evolved as one of the first metabolic pathways. It is important to note that glycolysis occurs in the cytoplasm of both prokaryotic and eukaryotic cells. (Remember that only eukaryotic cells have mitochondria.) Like all metabolic pathways, glycolysis occurs in steps or stages. In the first stage, the six-carbon ring of glucose is prepared for cleavage (“splitting”) into two three-carbon molecules by investing two molecules of ATP to energize the separation. (Don’t worry; the cell will get the investment of ATP back. It’s like the stock market: You have to invest money to, hopefully, make money!) As glucose is metabolized further, bonds are rearranged through a series of enzyme-catalyzed steps, and free energy is released to form ATP from ADP and free phosphate molecules. The availability of enzymes can affect the rate of glucose metabolism. Two molecules of pyruvate are
ultimately produced. High-energy electrons and hydrogen atoms pass to NAD+, reducing it to NADH. Although two molecules of ATP were invested to destabilize glucose at the beginning of the process, four molecules of ATP are formed by substrate-level phosphorylation, resulting in a net gain of two ATP and two NADH molecules for the cell. Information presented and the examples highlighted in the section support concepts and Learning Objectives outlined in This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 287 Big Idea 1 and Big Idea 2 of the AP® Biology Curriculum Framework, as shown in the table. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices. Big Idea 1 The process of evolution drives the diversity and unity of life. Enduring Understanding 1.B Organisms are linked by lines of descent from common ancestry. Essential Knowledge 1.B.1 Organisms share many conserved core processes and features that evolved and are widely distributed among organisms today. Science Practice 7.2 The student can connect concepts in and across domain(s) to generalize or extrapolate in and/or across enduring understandings and/or big ideas. Learning Objective Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Science Practice Learning Objective Essential Knowledge Science Practice Learning Objective 1.15 The student is able to describe specific examples of conserved core biological processes and features shared by all domains or within one domain of life, and how these shared, conserved core processes and features support the concept of common ancestry for all organisms. Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and maintenance of living systems require free energy and matter. 2.A.2 Organisms capture and store free energy for use in biological processes. 1.4 The student can use representations and models to analyze situations or solve problems qualitatively and quantitatively. 3.1 The student can pose scientific questions. 2.4 The student is able to use representations to pose scientific questions about what mechanisms and structural features allow organisms to capture, store, and use free energy. 2.A.2 Organisms capture and store free energy for use in biological processes. 6.2
The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.5 The student is able to construct explanations of the mechanisms and structural features of cells that allow organisms to capture, store, or use free energy. You have read that nearly all of the energy used by living cells comes to them in the bonds of the sugar, glucose. Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism. Nearly all living organisms carry out glycolysis as part of their metabolism. The process does not use oxygen and is therefore anaerobic. Glycolysis takes place in the cytoplasm of both prokaryotic and eukaryotic cells. Glucose enters heterotrophic cells in two ways. One method is through secondary active transport in which the transport takes place against the glucose concentration gradient. The other mechanism uses a group of integral proteins called GLUT proteins, also known as glucose transporter proteins. These transporters assist in the facilitated diffusion of glucose. Glycolysis begins with the six carbon ring-shaped structure of a single glucose molecule and ends with two molecules of a three-carbon sugar called pyruvate. Glycolysis consists of two distinct phases. The first part of the glycolysis pathway traps the glucose molecule in the cell and uses energy to modify it so that the six-carbon sugar molecule can be split evenly into the two three-carbon molecules. The second part of glycolysis extracts energy from the molecules and stores it in the form of ATP and NADH, the reduced form of NAD+. 288 Chapter 7 \| Cellular Respiration First Half of Glycolysis (Energy-Requiring Steps) Step 1. The first step in glycolysis (Figure 7.6) is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation of six-carbon sugars. Hexokinase phosphorylates glucose using ATP as the source of the phosphate, producing glucose-6-phosphate, a more reactive form of glucose. This reaction prevents the phosphorylated glucose molecule from continuing to interact with the GLUT proteins, and it can no longer leave the cell because the negatively charged phosphate will not allow it to cross the hydrophobic interior of the plasma membrane. Step 2. In the second step of glycolysis, an isomerase converts glucose-6-phosphate into one of its isomers, fructose-6-phosph
ate. An isomerase is an enzyme that catalyzes the conversion of a molecule into one of its isomers. (This change from phosphoglucose to phosphofructose allows the eventual split of the sugar into two three-carbon molecules.). Step 3. The third step is the phosphorylation of fructose-6-phosphate, catalyzed by the enzyme phosphofructokinase. A second ATP molecule donates a high-energy phosphate to fructose-6-phosphate, producing fructose-1,6-bisphosphate. In this pathway, phosphofructokinase is a rate-limiting enzyme. It is active when the concentration of ADP is high; it is less active when ADP levels are low and the concentration of ATP is high. Thus, if there is “sufficient” ATP in the system, the pathway slows down. This is a type of end product inhibition, since ATP is the end product of glucose catabolism. Step 4. The newly added high-energy phosphates further destabilize fructose-1,6-bisphosphate. The fourth step in glycolysis employs an enzyme, aldolase, to cleave fructose-1,6-bisphosphate into two three-carbon isomers: dihydroxyacetonephosphate and glyceraldehyde-3-phosphate. 5. In the Step isomer, glyceraldehyde-3-phosphate. Thus, the pathway will continue with two molecules of glyceraldehyde-3-phosphate. At this point in the pathway, there is a net investment of energy from two ATP molecules in the breakdown of one glucose molecule. dihydroxyacetone-phosphate transforms isomerase step, fifth into the its an Figure 7.6 The first half of glycolysis uses two ATP molecules in the phosphorylation of glucose, which is then split into two three-carbon molecules. Second Half of Glycolysis (Energy-Releasing Steps) So far, glycolysis has cost the cell two ATP molecules and produced two small, three-carbon sugar molecules. Both of these molecules will proceed through the second half of the pathway, and sufficient energy will be extracted to pay back the two ATP molecules used as an initial investment and produce a profit for the cell of two additional ATP molecules and two even higher-energy NADH molecules. Step 6. The sixth step in glycolysis (Figure
7.7) oxidizes the sugar (glyceraldehyde-3-phosphate), extracting high-energy electrons, which are picked up by the electron carrier NAD+, producing NADH. The sugar is then phosphorylated by the addition of a second phosphate group, producing 1,3-bisphosphoglycerate. Note that the second phosphate group does not require another ATP molecule. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 289 Figure 7.7 The second half of glycolysis involves phosphorylation without ATP investment (step 6) and produces two NADH and four ATP molecules per glucose. Here again is a potential limiting factor for this pathway. The continuation of the reaction depends upon the availability of the oxidized form of the electron carrier, NAD+. Thus, NADH must be continuously oxidized back into NAD+ in order to keep this step going. If NAD+ is not available, the second half of glycolysis slows down or stops. If oxygen is available in the system, the NADH will be oxidized readily, though indirectly, and the high-energy electrons from the hydrogen released in this process will be used to produce ATP. In an environment without oxygen, an alternate pathway (fermentation) can provide the oxidation of NADH to NAD+. Step 7. In the seventh step, catalyzed by phosphoglycerate kinase (an enzyme named for the reverse reaction), 1,3-bisphosphoglycerate donates a high-energy phosphate to ADP, forming one molecule of ATP. (This is an example of substrate-level phosphorylation.) A carbonyl group on the 1,3-bisphosphoglycerate is oxidized to a carboxyl group, and 3-phosphoglycerate is formed. Step 8. In the eighth step, the remaining phosphate group in 3-phosphoglycerate moves from the third carbon to the second carbon, producing 2-phosphoglycerate (an isomer of 3-phosphoglycerate). The enzyme catalyzing this step is a mutase (isomerase). Step 9. Enolase catalyzes the ninth step. This enzyme causes 2-phosphoglycerate to lose water from its structure; this is a dehydration reaction, resulting in the formation of a double bond that increases the potential energy in the remaining phosphate bond and
produces phosphoenolpyruvate (PEP). Step 10. The last step in glycolysis is catalyzed by the enzyme pyruvate kinase (the enzyme in this case is named for the reverse reaction of pyruvate’s conversion into PEP) and results in the production of a second ATP molecule by substratelevel phosphorylation and the compound pyruvic acid (or its salt form, pyruvate). Many enzymes in enzymatic pathways are named for the reverse reactions, since the enzyme can catalyze both forward and reverse reactions (these may have been described initially by the reverse reaction that takes place in vitro, under non-physiological conditions). Gain a better understanding of the breakdown of glucose by glycolysis by visiting this site (http://openstaxcollege.org/ l/glycolysis) to see the process in action. 290 Chapter 7 \| Cellular Respiration Glycolysis occurs in the cytoplasm of nearly every cell. Organisms, from the small, circular colonies of bacteria pictured here to the human holding the petri dish, perform glycolysis using the same ten enzymes. Because of this, it is thought that glycolysis must have evolved in the very earliest forms of life. Figure 7.8 ATP energy is needed for glycolysis. Explain how this ATP debt is paid off during the reaction. How is this ATP debt paid off during the reaction? a. by the phosphorylation of fructose-6-phosphate b. by the oxidation of glyceraldehyde-3-phosphate c. by the formation of 3-phosphoglycerate d. by the formation of phosphoenolpyruvate This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 291 Outcomes of Glycolysis Glycolysis starts with glucose and ends with two pyruvate molecules, a total of four ATP molecules and two molecules of NADH. Two ATP molecules were used in the first half of the pathway to prepare the six-carbon ring for cleavage, so the cell has a net gain of two ATP molecules and 2 NADH molecules for its use. If the cell cannot catabolize the pyruvate molecules further, it will harvest only two ATP molecules from one molecule of glucose. Mature mammalian red blood cells are not capable of aerobic
respiration—the process in which organisms convert energy in the presence of oxygen—and glycolysis is their sole source of ATP. If glycolysis is interrupted, these cells lose their ability to maintain their sodium-potassium pumps, and eventually, they die. The last step in glycolysis will not occur if pyruvate kinase, the enzyme that catalyzes the formation of pyruvate, is not available in sufficient quantities. In this situation, the entire glycolysis pathway will proceed, but only two ATP molecules will be made in the second half. Thus, pyruvate kinase is a rate-limiting enzyme for glycolysis. Think About It • Nearly all organisms on Earth carry out some form of glycolysis. How does that fact support or not support the assertion that glycolysis is one of the oldest metabolic pathways? Justify your answer. • Human red blood cells do not perform aerobic respiration, but they do perform glycolysis. What might happen if glycolysis were blocked in a red blood cell? Could red blood cells tap into other sources of free energy needed for their functions? 7.3 \| Oxidation of Pyruvate and the Citric Acid Cycle In this section, you will explore the following question: • How is pyruvate, the product of glycolysis, prepared for entry into the citric acid cycle? • What are the products of the citric acid cycle? Connection for AP® Courses In the next stage of cellular respiration—and in the presence of oxygen—pyruvate produced in glycolysis is transformed into an acetyl group attached to a carrier molecule of coenzyme A. The resulting acetyl CoA is usually delivered from the cytoplasm to the mitochondria, a process that uses some ATP. In the mitochondria, acetyl CoA continues on to the citric acid cycle. The citric acid cycle (CAC or TCA- tricarboxylic acid cycle) is also known as the Krebs cycle. During the conversion of pyruvate into the acetyl group, a molecule of CO2 and two high-energy electrons are removed. (Remember that glycolysis produces two molecules of pyruvate, and each can attach to a molecule of CoA and then enter the citric acid cycle. (A simple rule is to “count the carbons.
” Because matter and energy cannot be created or destroyed, we must account for everything.) The electrons are picked up by NAD+, and NADH carries the electrons to a later pathway (the electron transport chain described below) for ATP production. The glucose molecule that originally entered cellular respiration in glycolysis has been completely oxidized. Chemical potential energy stored within the glucose molecules has been transferred to NADH or has been used to synthesize ATP molecules. The citric acid cycle occurs in the mitochondrial matrix and involves a series of redox and decarboxylation reactions that again remove high energy electrons and produce CO2. These electrons are carried by NADH and FADH2 to the electron transport chain located in the cristae of the mitochondrion. (You do not need to memorize the steps in the citric acid cycle, but if provided with a diagram of the cycle, you should be able to interpret the steps.) During the cycle, ATP is synthesized from ADP and inorganic phosphate by substrate-level phosphorylation. 292 Chapter 7 \| Cellular Respiration Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Science Practice Learning Objective Essential Knowledge Science Practice Learning Objective Big Idea 4 Enduring Understanding 4.A Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and maintenance of living systems require free energy and matter. 2.A.2 Organisms capture and store free energy for use in biological processes. 1.4 The student can use representations and models to analyze situations or solve problems qualitatively and quantitatively. 3.1 The student can pose scientific questions. 2.4 The student is able to use representations to pose scientific questions about what mechanisms and structural features allow organisms to capture, store, and use free energy. 2.A.2 Organisms capture and store free energy for use in biological processes 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.5 The student is able to construct explanations of the mechanisms and structural features of cells that allow organisms to capture, store, or use free energy. Biological systems interact, and these systems and their interactions possess complex properties. Interactions within biological systems lead to complex properties. Essential Knowledge 4.A.2 The structure and function of subcellular components, and their interactions, provide essential cellular processes. Science Practice Learning Objective 1.4 The student can use representations and models to analyze situations or solve problems qualitatively
and quantitatively. 4.6 The student is able to use representations and models to analyze situations qualitatively to describe how interactions of subcellular structures, which possess specialized functions, provide essential functions. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.1][APLO 2.5][APLO 2.16][APLO 2.17][APLO 2.18] If oxygen is available, aerobic respiration will go forward. In eukaryotic cells, the pyruvate molecules produced at the end of glycolysis are transported into mitochondria. There, pyruvate will be transformed into an acetyl group that will be picked up and activated by a carrier compound called coenzyme A (CoA). The resulting compound is called acetyl CoA. CoA is made from vitamin B5, pantothenic acid. Acetyl CoA can be used in a variety of ways by the cell, but its major function is to deliver the acetyl group derived from pyruvate to the next stage of the pathway in glucose catabolism. Breakdown of Pyruvate In order for pyruvate, the product of glycolysis, to enter the next pathway, it must undergo several changes. The conversion is a three-step process (Figure 7.9). Step 1. A carboxyl group is removed from pyruvate, releasing a molecule of carbon dioxide into the surrounding medium. The result of this step is a two-carbon hydroxyethyl group bound to the enzyme (pyruvate dehydrogenase). This is the first of the six carbons from the original glucose molecule to be removed. This step proceeds twice (remember: there are two pyruvate molecules produced at the end of glycolsis) for every molecule of glucose metabolized; thus, two of the six carbons will have been removed at the end of both steps. This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 293 Step 2. The hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+, forming NADH. The high-energy electrons from NADH will be used later to generate ATP. Step 3. The enzyme-bound acetyl group is transferred to
CoA, producing a molecule of acetyl CoA. Figure 7.9 Upon entering the mitochondrial matrix, a multi-enzyme complex converts pyruvate into acetyl CoA. In the process, carbon dioxide is released and one molecule of NADH is formed. Note that during the second stage of glucose metabolism, whenever a carbon atom is removed, it is bound to two oxygen atoms, producing carbon dioxide, one of the major end products of cellular respiration. Acetyl CoA to CO2 In the presence of oxygen, acetyl CoA delivers its acetyl group to a four-carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups; this pathway will harvest the remainder of the extractable energy from what began as a glucose molecule. This single pathway is called by different names: the citric acid cycle (for the first intermediate formed—citric acid, or citrate—when acetate joins to the oxaloacetate), the TCA cycle (since citric acid or citrate and isocitrate are tricarboxylic acids), and the Krebs cycle, after Hans Krebs, who first identified the steps in the pathway in the 1930s in pigeon flight muscles. Citric Acid Cycle Like the conversion of pyruvate to acetyl CoA, the citric acid cycle takes place in the matrix of mitochondria. Almost all of the enzymes of the citric acid cycle are soluble, with the single exception of the enzyme succinate dehydrogenase, which is embedded in the inner membrane of the mitochondrion. Unlike glycolysis, the citric acid cycle is a closed loop: The last part of the pathway regenerates the compound used in the first step. The eight steps of the cycle are a series of redox, dehydration, hydration, and decarboxylation reactions that produce two carbon dioxide molecules, one GTP/ATP, and reduced forms of NADH and FADH2 (Figure 7.10). This is considered an aerobic pathway because the NADH and FADH2 produced must transfer their electrons to the next pathway in the system, which will use oxygen. If this transfer does not occur, the oxidation steps of the citric acid cycle also do not occur. Note that the citric acid cycle produces very little ATP directly and does not directly consume oxygen. 294 Chapter 7 \| Cellular Respiration Figure 7.10 In the citric acid cycle
, the acetyl group from acetyl CoA is attached to a four-carbon oxaloacetate molecule to form a six-carbon citrate molecule. Through a series of steps, citrate is oxidized, releasing two carbon dioxide molecules for each acetyl group fed into the cycle. In the process, three NAD+ molecules are reduced to NADH, one FAD molecule is reduced to FADH2, and one ATP or GTP (depending on the cell type) is produced (by substrate-level phosphorylation). Because the final product of the citric acid cycle is also the first reactant, the cycle runs continuously in the presence of sufficient reactants. (credit: modification of work by “Yikrazuul”/Wikimedia Commons) Steps in the Citric Acid Cycle Step 1. Prior to the start of the first step, a transitional phase occurs during which pyruvic acid is converted to acetyl CoA. Then, the first step of the cycle begins: This is a condensation step, combining the two-carbon acetyl group with a fourcarbon oxaloacetate molecule to form a six-carbon molecule of citrate. CoA is bound to a sulfhydryl group (-SH) and diffuses away to eventually combine with another acetyl group. This step is irreversible because it is highly exergonic. The rate of this reaction is controlled by negative feedback and the amount of ATP available. If ATP levels increase, the rate of this reaction decreases. If ATP is in short supply, the rate increases. Step 2. In step two, citrate loses one water molecule and gains another as citrate is converted into its isomer, isocitrate. Step 3. In step three, isocitrate is oxidized, producing a five-carbon molecule, α-ketoglutarate, together with a molecule of CO2 and two electrons, which reduce NAD+ to NADH. This step is also regulated by negative feedback from ATP and NADH, and a positive effect of ADP. Steps 3 and 4. Steps three and four are both oxidation and decarboxylation steps, which release electrons that reduce NAD+ to NADH and release carboxyl groups that form CO2 molecules. α-Ketoglutarate is the product of step three, and a succinyl group is the product of step four. CoA binds the succinyl group to form succinyl CoA. The enzyme that catalyzes step four This
OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 295 is regulated by feedback inhibition of ATP, succinyl CoA, and NADH. Step 5. In step five, a phosphate group is substituted for coenzyme A, and a high-energy bond is formed. This energy is used in substrate-level phosphorylation (during the conversion of the succinyl group to succinate) to form either guanine triphosphate (GTP) or ATP. There are two forms of the enzyme, called isoenzymes, for this step, depending upon the type of animal tissue in which they are found. One form is found in tissues that use large amounts of ATP, such as heart and skeletal muscle. This form produces ATP. The second form of the enzyme is found in tissues that have a high number of anabolic pathways, such as liver tissues. This form produces GTP. GTP is energetically equivalent to ATP; however, its use is more restricted. In particular, protein synthesis primarily uses GTP. Step 6. Step six is a dehydration process that converts succinate into fumarate. Two hydrogen atoms are transferred to FAD, producing FADH2. The energy contained in the electrons of these atoms is insufficient to reduce NAD+ but adequate to reduce FAD. Unlike NADH, this carrier remains attached to the enzyme and transfers the electrons to the electron transport chain directly. This process is made possible by the localization of the enzyme catalyzing this step inside the inner membrane of the mitochondrion. Step 7. Water is added to fumarate during step seven, and malate is produced. The last step in the citric acid cycle regenerates oxaloacetate by oxidizing malate. Another molecule of NADH is produced in the process. Click through each step of the citric acid cycle here (http://openstaxcollege.org/l/krebs_cycle). Why is the mitochondria considered the powerhouse of the cell? a. Glycolysis takes place in mitochondria which extract energy by glucose breakdown for cellular metabolism. b. Most of the ATP is produced in mitochondria by oxidative phosphorylation. c. All the pathways involved in ATP production take place in the mitochondria. d. The outer membrane of mitochondria is loaded with proteins involved in electron transfer and ATP synthesis. Products of the Citric Acid Cycle
Two carbon atoms come into the citric acid cycle from each acetyl group, representing four out of the six carbons of one glucose molecule. Two carbon dioxide molecules are released on each turn of the cycle; however, these do not necessarily contain the most recently added carbon atoms. The two acetyl carbon atoms will eventually be released on later turns of the cycle; thus, all six carbon atoms from the original glucose molecule are eventually incorporated into carbon dioxide. Each turn of the cycle forms three NADH molecules and one FADH2 molecule. These carriers will connect with the last portion of aerobic respiration to produce ATP molecules. One GTP or ATP is also made in each cycle. Several of the intermediate compounds in the citric acid cycle can be used in synthesizing non-essential amino acids; therefore, the cycle is amphibolic (both catabolic and anabolic). Think About It Explain how citrate from the citric acid cycle might affect glycolysis. What other factors might affect the efficiency of the citric acid cycle and its products? 296 Chapter 7 \| Cellular Respiration 7.4 \| Oxidative Phosphorylation In this section, you will explore the following questions: • How do electrons move through the electron transport chain and what happens to their energy levels? • How is a proton (H+) gradient established and maintained by the electron transport chain and how many ATP molecules are produced by chemiosmosis? Connection for AP® Courses The electron transport chain (ETC) is the stage of aerobic respiration that uses free oxygen as the final electron acceptor of the electrons removed during glucose metabolism in glycolysis and the citric acid cycle. The ETC is located in membrane of the mitochondrial cristae, an area with many folds that increase the surface area available for chemical reactions. Electrons carried by NADH and FADH2 are delivered to electron acceptor proteins embedded in the membrane as they move toward the final electron acceptor, O2, forming water. The electrons pass through a series of redox reactions, using free energy at three points to transport hydrogen ions across the membrane. This process contributes to the formation of the H+ gradient used in chemiosmosis. As the protons are driven down their concentration gradient through ATP synthase, ATP is generated from ADP and inorganic phosphate. Under aerobic conditions, the stages of cellular respiration can generate 36-38 ATP. Information presented and the examples highlighted in the section support concepts outlined in Big Idea 2 of
the AP® Biology Curriculum Framework, as shown in the table. As shown in the table, concepts covered in this section also align to the Learning Objectives listed in the Curriculum Framework that provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices. Big Idea 2 Enduring Understanding 2.A Essential Knowledge Science Practice Science Practice Learning Objective Essential Knowledge Science Practice Learning Objective Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis. Growth, reproduction and maintenance of living systems require free energy and matter. 2.A.1 All living systems require constant input of free energy. 1.4 The student can use representations and models to analyze situations or solve problems qualitatively and quantitatively. 3.1 The student can pose scientific questions. 2.4 The student is able to use representations to pose scientific questions about what mechanisms and structural features allow organisms to capture, store, and use free energy. 2.A.1 All living systems require constant input of free energy. 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices. 2.5 The student is able to construct explanations of the mechanisms and structural features of cells that allow organisms to capture, store, or use free energy. The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards: [APLO 2.5][APLO 2.15][APLO 2.18][APLO 2.22] You have just read about two pathways Introduce glucose catabolism—glycolysis and the citric acid cycle—that generate ATP. Most of the ATP generated during the aerobic catabolism of glucose, however, is not generated directly from these This OpenStax book is available for free at http://cnx.org/content/col12078/1.6 Chapter 7 \| Cellular Respiration 297 pathways. Rather, it is derived from a process that begins with moving electrons through a series of electron transporters that undergo redox reactions. This causes hydrogen ions to accumulate within the matrix space. Therefore, a concentration gradient forms in which hydrogen ions diffuse out of the matrix space by passing through ATP synthase. The current of hydrogen ions powers the catalytic action of ATP synthase, which phosphorylates AD
P, producing ATP. Electron Transport Chain The electron transport chain (Figure 7.11) is the last component of aerobic respiration and is the only part of glucose metabolism that uses atmospheric oxygen. Oxygen continuously diffuses into plants; in animals, it enters the body through the respiratory system. Electron transport is a series of redox reactions that resemble a relay race or bucket brigade in that electrons are passed rapidly from one component to the next, to the endpoint of the chain where the electrons reduce molecular oxygen, producing water. There are four complexes composed of proteins, labeled I through IV in Figure 7.11, and the aggregation of these four complexes, together with associated mobile, accessory electron carriers, is called the electron transport chain. The electron transport chain is present in multiple copies in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes. Figure 7.11 The electron transport chain is a series of electron transporters embedded in the inner mitochondrial membrane that shuttles electrons from NADH and FADH2 to molecular oxygen. In the process, protons are pumped from the mitochondrial matrix to the intermembrane space, and oxygen is reduced to form water. Complex I To start, two electrons are carried to the first complex aboard NADH. This complex, labeled I, is composed of flavin mononucleotide (FMN) and an iron-sulfur (Fe-S)-containing protein. FMN, which is derived from vitamin B2, also called riboflavin, is one of several prosthetic groups or co-factors in the electron transport chain. A prosthetic group is a nonprotein molecule required for the activity of a protein. Prosthetic groups are organic or inorganic, non-peptide molecules bound to a protein that facilitate its function; prosthetic groups include co-enzymes, which are the prosthetic groups of enzymes. The enzyme in complex I is NADH dehydrogenase and is a very large protein, containing 45 amino acid chains. Complex I can pump four hydrogen ions across the membrane from the matrix into the intermembrane space, and it is in this way that the hydrogen ion gradient is established and maintained between the two compartments separated by the inner mitochondrial membrane. Q and Complex II Complex II directly receives FADH2, which does not pass through complex I. The compound connecting the first and second complexes to the third is ubiquinone (Q). The Q molecule is lipid soluble and freely

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