BCH 202 Note 2022 PDF

6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... 6.2: Energy and Metabolism What you’ll learn to do: Discuss energy and metabolism in living things Scie...

6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... 6.2: Energy and Metabolism What you’ll learn to do: Discuss energy and metabolism in living things Scientists use the term bioenergetics to describe the concept of energy flow (Figure 1) 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. Figure 1. Ultimately, most life forms get their energy from the sun. Plants use photosynthesis to capture sunlight, and herbivores eat the plants to obtain energy. Carnivores eat the herbivores, and eventual decomposition of plant and animal material contributes to the nutrient pool. Just as living things must continually consume food to replenish their energy supplies, cells must continually produce more energy to replenish that used by the many energy-requiring chemical reactions that constantly take place. Together, all of the chemical reactions that take place inside cells, including those that consume or generate energy, are referred to as the cell’s metabolism. Learning Objectives Identify different types of metabolic pathways Distinguish between an open and a closed system State the first law of thermodynamics State the second law of thermodynamics Explain the difference between kinetic and potential energy Describe endergonic and exergonic reactions Discuss how enzymes function as molecular catalysts Metabolic Pathways Consider the metabolism of sugar. This is a classic example of one of the many cellular processes that use and produce energy. Living things consume sugars as a major energy source, because sugar molecules have a great deal of energy stored within their bonds. For the most part, photosynthesizing organisms like plants produce these sugars. During photosynthesis, plants use energy (originally from sunlight) to convert carbon dioxide gas (CO2) into sugar molecules (like glucose: C6H12O6). They consume carbon dioxide and produce oxygen as a waste product. This reaction is summarized as: Because this process involves synthesizing an energy-storing molecule, it requires energy input to proceed. During the light reactions of photosynthesis, energy is provided by a molecule called adenosine triphosphate (ATP), 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. In contrast, energy-storage molecules such as glucose are consumed only to be broken down to use their energy. The reaction that harvests the energy of a sugar molecule in cells requiring oxygen to survive can be summarized by the reverse reaction to photosynthesis. In this reaction, oxygen is consumed and carbon dioxide is released as a waste product. The reaction is summarized as: Both of these reactions involve many steps. The processes of making and breaking down sugar molecules illustrate two examples of metabolic pathways. A metabolic pathway is a series of chemical reactions that takes a starting molecule and modifies it, step-by-step, through a series of metabolic intermediates, eventually yielding a 1 of 7 07/06/2022, 16:49 6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... final product. In the example of sugar metabolism, the first metabolic pathway synthesized sugar from smaller molecules, and the other pathway broke sugar down into smaller molecules. These two opposite processes—the first requiring energy and the second producing energy—are referred to as anabolic pathways (building polymers) and catabolic pathways (breaking down polymers into their monomers), respectively. Consequently, metabolism is composed of synthesis (anabolism) and degradation (catabolism) (Figure 2). Figure 2. Catabolic pathways are those that generate energy by breaking down larger molecules. Anabolic pathways are those that require energy to synthesize larger molecules. Both types of pathways are required for maintaining the cell’s energy balance. It is important to know that the chemical reactions of metabolic pathways do not take place on their own. 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. Thermodynamics Thermodynamics refers to the study of energy and energy transfer involving physical matter. The matter relevant to a particular case of energy transfer is called a system, and everything outside of that matter 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 and closed. In an open system, both energy and matter can be exchanged with its surroundings. The stovetop system is open because heat and water molecules (now in gas form) can be lost to the air. If you put a lid on the pot of water, it becomes a closed system. In this closed system, matter cannot be exchanged, but energy can be. Biological organisms are open systems. Energy is exchanged between them and their surroundings as they use energy from the sun to perform photosynthesis or consume energy-storing molecules and release energy to the environment by doing work and releasing heat. Like all things in the physical world, energy is subject to physical laws. The laws of thermodynamics govern the transfer of energy in and among all systems in the universe. In general, energy is defined as the ability to do work, or to create some kind of change. Energy exists in different forms. For example, electrical energy, light energy, and heat energy are all different types of energy. To appreciate the way energy flows into and out of biological systems, it is important to understand two of the physical laws that govern energy. The First Law of Thermodynamics The first law of thermodynamics states that the total amount of energy in the universe is constant and conserved. 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 and heat 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 to chemical energy stored within organic molecules (Figure 3). Some examples of energy transformations are shown in (Figure 3). 2 of 7 07/06/2022, 16:49 6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... Figure 3. Shown are some examples of energy transferred and transformed from one system to another and from one form to another. The food we consume provides our cells with the energy required to carry out bodily functions, just as light energy provides plants with the means to create the chemical energy they need. (credit “ice cream”: modification of work by D. Sharon Pruitt; credit “kids”: modification of work by Max from Providence; credit “leaf”: modification of work by Cory Zanker) 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. The Second Law of Thermodynamics Figure 4. Entropy is a measure of randomness or disorder in a system. Gases have higher entropy than liquids, and liquids have higher entropy than solids. 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. Chemical energy stored within organic molecules such as sugars and fats is transferred and 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 motion of cilia or flagella, and contracting muscle fibers to create movement. A living cell’s primary tasks of obtaining, transforming, and using energy to do work may seem simple. However, the second law of thermodynamics explains why these tasks are harder than they appear. All energy transfers and transformations are never 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 work. For example, when a light bulb is turned on, some of the energy being converted from electrical energy into light energy is lost as heat energy. Likewise, some energy is lost as heat energy during cellular metabolic reactions. Try It Yourself 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? An important concept in physical systems is that of order and disorder. 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. Molecules and chemical reactions have varying entropy as well. For example, entropy increases as molecules at a high concentration in one place diffuse and spread out. The second law of thermodynamics says that energy will always be lost as heat in energy transfers or transformations. 3 of 7 07/06/2022, 16:49 6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... Living things are highly ordered, requiring constant energy input to be maintained in a state of low entropy. Energy Potential and Kinetic Energy When an object is in motion, there is energy associated with that object. Think of a wrecking ball. Even a slow-moving wrecking ball can do a great deal of damage to other objects. Energy associated with objects in motion is called kinetic energy (Figure 5). A speeding bullet, a walking person, and the rapid movement of molecules in the air (which produces heat) all have kinetic energy. Figure 5. Still water 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) Now what if that same motionless wrecking ball is lifted two stories above ground with a crane? If the suspended wrecking ball is unmoving, is there energy associated with it? The answer is yes. The energy that was required to lift the wrecking ball did not disappear, but is now stored in the wrecking ball by virtue of its position and the force of gravity acting on it. This type of energy is called potential energy (Figure 5). If the ball were to fall, the potential energy would be transformed into kinetic energy until all of the potential energy was exhausted when the ball rested on the ground. Wrecking balls also swing like a pendulum; through the swing, there is a constant change of potential energy (highest at the top of the swing) to kinetic energy (highest at the bottom of the swing). Other examples of potential energy include the energy of water held behind a dam or a person about to skydive out of an airplane. Potential energy is not only associated with the location of matter, but also with the structure of matter. Even a spring on the ground has potential energy if it is compressed; so does a rubber band that is pulled taut. On a molecular level, the bonds that hold the atoms of molecules together exist in a particular structure that has 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. Chemical energy is responsible for providing living cells with energy from food. The release of energy occurs when the molecular bonds within food molecules are broken. Free and Activation Energy After learning that chemical reactions release energy when energy-storing bonds are broken, an important next question is the following: How is the energy associated with these chemical reactions quantified and expressed? How can the energy released from one reaction be compared to that of another reaction? A measurement of free energy is used to quantify these energy transfers. 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. Free energy specifically refers to the energy associated with a chemical reaction that is available after the losses are accounted for. In other words, free energy is usable energy, or energy that is available to do work. If energy is released during a chemical reaction, then the change in free energy, signified as G (delta G) will be a negative number. A negative change in free energy also means that the products of the reaction have less free energy than the reactants, because they release some free energy during the reaction. Reactions that have a negative change in free energy 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, and their products have less stored energy than the reactants. An important distinction must be drawn between the term spontaneous and the idea of a chemical reaction occurring 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 absorbs energy rather than releases energy on balance, 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 non-spontaneous. An endergonic reaction will not take place on its own without the addition of free energy. There is another important concept that must be considered regarding endergonic and exergonic reactions. 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 input in the beginning. This small amount of energy input necessary for all chemical reactions to occur is called the activation energy. 4 of 7 07/06/2022, 16:49 6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... Enzymes Figure 6. Enzymes lower the activation energy of the reaction but do not change the free energy of the reaction. A substance that helps a chemical reaction to occur is called a catalyst, and the molecules that catalyze biochemical reactions are called enzymes. Most enzymes are proteins and perform the critical task of lowering the activation energies of chemical reactions inside the cell. Most of the reactions critical to a living cell happen too slowly at normal temperatures to be of any use to the cell. Without enzymes to speed up these reactions, life could not persist. Enzymes do this by binding to the reactant molecules and holding them in such a way as to make the chemical bond-breaking and -forming processes take place more easily. It is important to remember that enzymes do not change whether a reaction is exergonic (spontaneous) or endergonic. This is because they do not change the free energy of the reactants or products. They only reduce the activation energy required for the reaction to go forward (Figure 6). In addition, an enzyme itself is unchanged by the reaction it catalyzes. Once one reaction has been catalyzed, the enzyme is able to participate in other reactions. The chemical reactants to which an enzyme binds are called 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 and both become modified, but they 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. Since enzymes are proteins, there is a unique combination of amino acid side chains within the active site. Each side chain is characterized by different properties. They can be large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral. The unique combination of side chains creates a very specific chemical environment within the active site. This specific environment is suited to bind to one specific chemical substrate (or substrates). Active sites are subject to influences of the local environment. Increasing the environmental temperature generally increases reaction rates, enzyme-catalyzed or otherwise. However, temperatures outside of an optimal range reduce the rate at which an enzyme catalyzes a reaction. Hot temperatures will eventually cause enzymes to denature, an irreversible change in the three-dimensional shape and therefore the function of the enzyme. Enzymes are also suited to function best within a certain pH and salt concentration range, and, as with temperature, extreme pH, and salt concentrations can cause enzymes to denature. 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 model called induced fit (Figure 7). The induced-fit model expands on the lock-and-key model by describing a more dynamic binding between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that forms an ideal binding arrangement between enzyme and substrate. View this animation of induced fit. 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 multiple possible ways. On a basic level, enzymes promote chemical reactions that involve more than one substrate by bringing the substrates together in an optimal orientation for reaction. 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. 5 of 7 07/06/2022, 16:49 6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... Figure 7. The induced-fit model is an adjustment to the lock-and-key model and explains how enzymes and substrates undergo dynamic modifications during the transition state to increase the affinity of the substrate for the active site. Try It Figure 8. Have you ever wondered how pharmaceutical drugs are developed? (credit: Deborah Austin) Enzymes are key components of metabolic pathways. Understanding how enzymes work and how they can be regulated are key principles behind the development of many of the pharmaceutical drugs on the market today. Biologists working in this field collaborate with other scientists to design drugs. Consider statins for example—statins is the name given to one class of drugs that can reduce cholesterol levels. These compounds are inhibitors of the enzyme HMG-CoA reductase, which is the enzyme that synthesizes cholesterol from lipids in the body. By inhibiting this enzyme, the level of cholesterol synthesized in the body can be reduced. Similarly, acetaminophen, popularly marketed under the brand name Tylenol, is an inhibitor of the enzyme cyclooxygenase. While it is used to provide relief from fever and inflammation (pain), its mechanism of action is still not completely understood. How are drugs discovered? One of the biggest challenges in drug discovery is identifying a drug target. A drug target is a molecule that is literally the target of the drug. 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 enough; 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. In this stage, chemists and biologists work together to design and synthesize molecules that can block or activate a particular reaction. However, this is only the beginning: If and when a drug prototype is successful in performing its function, then it is subjected to many tests from in vitro experiments to clinical trials before it can get approval from the U.S. Food and Drug Administration to be on the market. Many enzymes do not work optimally, or even at all, unless bound to other specific non-protein helper molecules. They may bond either temporarily through ionic or hydrogen bonds, or permanently through stronger covalent bonds. Binding to these molecules promotes optimal shape and function of their respective enzymes. Two examples of these types of helper molecules are cofactors and coenzymes. Cofactors are inorganic ions such as ions of iron and magnesium. Coenzymes are organic helper molecules, those with a basic atomic structure made up of carbon and hydrogen. Like enzymes, these molecules participate in reactions without being changed themselves and are ultimately recycled and reused. Vitamins are the source of coenzymes. Some vitamins are the precursors of coenzymes and others act directly as coenzymes. Vitamin C is a direct coenzyme for multiple enzymes that take part in building the important connective tissue, collagen. Therefore, enzyme function is, in part, regulated by the abundance of various cofactors and coenzymes, which may be supplied by an organism’s diet or, in some cases, produced by the organism. Summary Cells perform the functions of life through various chemical reactions. A cell’s metabolism refers to the combination of chemical reactions that take place within it. Catabolic reactions break down complex chemicals into simpler ones and are associated with energy release. Anabolic processes build complex molecules out of simpler ones and require energy. In studying energy, the term system refers to the matter and environment involved in energy transfers. Entropy is a measure of the disorder of a system. The physical laws that describe the transfer of energy are the laws of thermodynamics. The first law states that the total amount of energy in the universe is constant. The second law of thermodynamics states that every energy transfer involves some loss of energy in an unusable form, such as heat energy. Energy comes in different forms: kinetic, potential, and free. The change in free energy of a reaction can be negative (releases energy, exergonic) or positive (consumes energy, endergonic). All reactions require an initial input of energy to proceed, called the activation energy. Enzymes are chemical catalysts that speed up chemical reactions by lowering their activation energy. Enzymes have an active site with a unique chemical environment that fits particular chemical reactants for that enzyme, called substrates. Enzymes and substrates are thought to bind according to an induced-fit model. Enzyme action is regulated to conserve resources and respond optimally to the environment. Practice Questions 1. Look at each of the processes shown in Figure 9, and decide if it is endergonic or exergonic. 6 of 7 07/06/2022, 16:49 6.2: Energy and Metabolism - Biology LibreTexts https://bio.libretexts.org/Courses/Lumen_Learning/Book%3A_Biolog... Figure 9. Shown are some examples of endergonic processes (ones that require energy) and exergonic processes (ones that release energy). (credit a: modification of work by Natalie Maynor; credit b: modification of work by USDA; credit c: modification of work by Cory Zanker; credit d: modification of work by Harry Malsch) 2. Does physical exercise to increase muscle mass involve anabolic and/or catabolic processes? Give evidence for your answer. 3. Explain in your own terms the difference between a spontaneous reaction and one that occurs instantaneously, and what causes this difference. 4. With regard to enzymes, why are vitamins and minerals necessary for good health? Give examples. Show Answers 1. A compost pile decomposing is an exergonic process. A baby developing from a fertilized egg is an endergonic process. Tea dissolving into water is an exergonic process. A ball rolling downhill is an exergonic process. 2. Physical exercise involves both anabolic and catabolic processes. Body cells break down sugars to provide ATP to do the work necessary for exercise, such as muscle contractions. This is catabolism. Muscle cells also must repair muscle tissue damaged by exercise by building new muscle. This is anabolism. 3. A spontaneous reaction is one that has a negative G and thus releases energy. However, a spontaneous reaction need not occur quickly or suddenly like an instantaneous reaction. It may occur over long periods of time due to a large energy of activation, which prevents the reaction from occurring quickly. 4. Most vitamins and minerals act as cofactors and coenzymes for enzyme action. Many enzymes require the binding of certain cofactors or coenzymes to be able to catalyze their reactions. Since enzymes catalyze many important reactions, it is critical to obtain sufficient vitamins and minerals from diet and supplements. Vitamin C (ascorbic acid) is a coenzyme necessary for the action of enzymes that build collagen. Check Your Understanding Answer the question(s) below to see how well you understand the topics covered in the previous section. This short quiz does not count toward your grade in the class, and you can retake it an unlimited number of times. Use this quiz to check your understanding and decide whether to (1) study the previous section further or (2) move on to the next section. https://assessments.lumenlearning.co...sessments/6876 CC licensed content, Shared previously Concepts of Biology. Provided by: Open Stax. Located at: http://cnx.org/contents/[email protected]. License: CC BY: Attribution. License Terms: Download for free at http://cnx.org/contents/[email protected] Biology. Provided by: OpenStax CNX. Located at: http://cnx.org/contents/[email protected]. License: CC BY: Attribution. License Terms: Download for free at http://cnx.org/contents/[email protected] 6.2: Energy and Metabolism is shared under a CC BY license and was authored, remixed, and/or curated by LibreTexts. 7 of 7 07/06/2022, 16:49 CHAPTER 6 Thermodynamics – II 293  Law of Mass Action and Its Thermodynamic Derivation According to the law of mass action, the rate of a chemical reaction is directly proportional to the product of the activities or simply the active masses of the reactants each term raised to its stoichiometric coefficients. To understand the law of mass action in mathematical language, consider a reaction in which two reactants A and B react to form the product C and D i.e. 𝑎𝐴 + 𝑏𝐵 → 𝑐𝐶 + 𝑑𝐷 (33) Then the law of mass action says the rate of the above conversion should be 𝑅𝑎𝑡𝑒 ∝ [𝐴]𝑎 [𝐵]𝑏 (34) 𝑅𝑎𝑡𝑒 = 𝑘[𝐴]𝑎 [𝐵]𝑏 (35) Where k is the constant of proportionality and is typically labeled as rate constant of the reaction. However, the actual rate of the reaction may or may not be equal to what is suggested by the “law of mass action” because the actual rate law may have powers raised to the active masses different from their stoichiometric coefficients. Mathematically, the actual rate law for the reaction given by equation (33) is 𝑅𝑎𝑡𝑒 ∝ [𝐴]𝛼 [𝐵]𝛽 (36) 𝑅𝑎𝑡𝑒 = 𝑘[𝐴]𝛼 [𝐵]𝛽 (37) Now comparing equation (35) and equation (37); the law of mass action and actual rate law will give same results when 𝑎 = 𝛼 and 𝑏 = 𝛽; whereas different results will be observed when 𝑎 ≠ 𝛼 and 𝑏 ≠ 𝛽.  Modern Definition of the Law of Mass Action The law of mass action can be used to study the composition of a mixture in a reversible reaction under equilibrium conditions. To do so, consider a typical reversible reaction i.e. 𝑎𝐴 + 𝑏𝐵 ⇌ 𝑐𝐶 + 𝑑𝐷 (38) Now, from the law of mass action, we know that the rate of forward reaction (Rf) and rate backward reaction (Rb) will be 𝑅𝑓 = 𝑘𝑓 [𝐴]𝑎 [𝐵]𝑏 (39) 𝑅𝑏 = 𝑘𝑏 [𝐶]𝑐 [𝐷]𝑑 (40) Where 𝑘𝑓 and 𝑘𝑏 are the rate constants for the forward and backward reactions, respectively. After equilibrium is reached, we have 𝑅𝑓 = 𝑅𝑏 (41) Copyright © Mandeep Dalal  294 A Textbook of Physical Chemistry – Volume I 𝑘𝑓 [𝐴]𝑎 [𝐵]𝑏 = 𝑘𝑏 [𝐶]𝑐 [𝐷]𝑑 (42) or 𝑘𝑓 [𝐶]𝑐 [𝐷]𝑑 (43) = 𝑘𝑏 [𝐴]𝑎 [𝐵]𝑏 Since the 𝑘𝑓 and 𝑘𝑏 are also constant at equilibrium, the ratio of the two is also a constant and is typically labeled as K or the equilibrium constant. Therefore, equation (43) is modified as 𝑘𝑓 [𝐶]𝑐 [𝐷]𝑑 (44) 𝐾= = 𝑘𝑏 [𝐴]𝑎 [𝐵]𝑏 All this leads to the modern definition of “law of mass action” that the ratio of the multiplication of molar concentrations of products raised to the power of their stoichiometric coefficients to the multiplication of the molar concentrations of the reactants raised to the power of their stoichiometric coefficients is constant at constant temperature and is called as “equilibrium constant”. It is also worthy to mention that equation (44) is also known as the “law of chemical equilibrium”.  Thermodynamic Derivation of the Law of Mass Action In order to derive the law of mass action thermodynamically, recall the general form of a typical reversible reaction under equilibrium conditions in which reactants and products are ideal gases i.e. 𝑎𝐴 + 𝑏𝐵 ⇌ 𝑐𝐶 + 𝑑𝐷 (45) Now, as we know that the total free energy of the reactant (𝐺𝑅 ) can be formulated as 𝐺𝑅 = 𝑎𝜇𝐴 + 𝑏𝜇𝐵 (46) Where 𝜇𝐴 and 𝜇𝐵 are the chemical potentials of reactant A and B, respectively. Similarly, the total free energy of the products (𝐺𝑃 ) can also be formulated i.e. 𝐺𝑃 = 𝑐𝜇𝐶 + 𝑑𝜇𝐷 (47) It is also important to mention that the temperature and pressure are kept constant. Moreover, the free energy change of the whole reaction can be obtained by subtracting equation (46) from equation (47) i.e. 𝛥𝐺𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛 = 𝐺𝑃 − 𝐺𝑅 (48) 𝛥𝐺𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛 = (𝑐𝜇𝐶 + 𝑑𝜇𝐷 ) − (𝑎𝜇𝐴 + 𝑏𝜇𝐵 ) (49) Recalling the fact that the free energy change at equilibrium is zero, equation (49) is reduced to (𝑐𝜇𝐶 + 𝑑𝜇𝐷 ) − (𝑎𝜇𝐴 + 𝑏𝜇𝐵 ) = 0 (51) Now recall the expression of the chemical potential of the ith species in gas phase i.e. Buy the complete book with TOC navigation, Copyright © Mandeep Dalal high resolution images and no watermark.  CHAPTER 6 Thermodynamics – II 295 𝜇𝑖 = 𝜇𝑖0 + 𝑅𝑇 ln 𝑝𝑖 (52) Where 𝑝𝑖 and 𝜇𝑖0 are the partial pressure and standard chemical potential of ith species, respectively. Now using equation (52) in equation (51), we get [𝑐(𝜇𝐶0 + 𝑅𝑇 ln 𝑝𝐶 ) + 𝑑(𝜇𝐷0 + 𝑅𝑇 ln 𝑝𝐷 )] − [𝑎(𝜇𝐴0 + 𝑅𝑇 ln 𝑝𝐴 ) + 𝑏(𝜇𝐵0 + 𝑅𝑇 ln 𝑝𝐵 )] = 0 (53) or 𝑐𝜇𝐶0 + 𝑐𝑅𝑇 ln 𝑝𝐶 + 𝑑𝜇𝐷0 + 𝑑𝑅𝑇 ln 𝑝𝐷 − 𝑎𝜇𝐴0 − 𝑎𝑅𝑇 ln 𝑝𝐴 − 𝑏𝜇𝐵0 − 𝑏𝑅𝑇 ln 𝑝𝐵 = 0 (54) 𝑐𝜇𝐶0 + 𝑅𝑇 ln 𝑝𝐶𝑐 + 𝑑𝜇𝐷0 + 𝑅𝑇 ln 𝑝𝐷𝑑 − 𝑎𝜇𝐴0 − 𝑅𝑇 ln 𝑝𝐴𝑎 − 𝑏𝜇𝐵0 − 𝑅𝑇 ln 𝑝𝐵𝑏 = 0 (55) 𝑅𝑇 ln 𝑝𝐶𝑐 + 𝑅𝑇 ln 𝑝𝐷𝑑 − 𝑅𝑇 ln 𝑝𝐴𝑎 − 𝑅𝑇 ln 𝑝𝐵𝑏 = −𝑐𝜇𝐶0 − 𝑑𝜇𝐷0 + 𝑎𝜇𝐴0 + 𝑏𝜇𝐵0 or 𝑅𝑇 ln (𝑝𝐶𝑐 𝑝𝐷𝑑 ) − 𝑅𝑇 ln (𝑝𝐴𝑎 𝑝𝐵𝑏 ) = −[𝑐𝜇𝐶0 + 𝑑𝜇𝐷0 − 𝑎𝜇𝐴0 − 𝑏𝜇𝐵0 ] (56) (𝑝𝐶𝑐 𝑝𝐷𝑑 ) (57) 𝑅𝑇 ln = −[𝐺𝑃𝑜 − 𝐺𝑅𝑜 ] (𝑝𝐴𝑎 𝑝𝐵𝑏 ) (𝑝𝐶𝑐 𝑝𝐷𝑑 ) 𝑜 (58) 𝑅𝑇 ln = −𝛥𝐺𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛 (𝑝𝐴𝑎 𝑝𝐵𝑏 ) Where 𝛥𝐺𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛 𝑜 is the standard free energy change of the reaction can be simply abbreviated as 𝛥𝐺 𝑜 only. Therefore, the equation (58) can be rearranged as given below. (𝑝𝐶𝑐 𝑝𝐷𝑑 ) 𝛥𝐺 𝑜 (59) ln =− (𝑝𝐴𝑎 𝑝𝐵𝑏 ) 𝑅𝑇 𝑝𝐶𝑐 𝑝𝐷𝑑 − 𝛥𝐺 𝑜 (61) = 𝑒 𝑅𝑇 𝑝𝐴𝑎 𝑝𝐵𝑏 Now because 𝛥𝐺 𝑜 is a function of temperature only and R is a constant quantity, the right-hand side can be put equal to another constant, say ‘Kp’. 𝛥𝐺 𝑜 (62) 𝑒 − 𝑅𝑇 = 𝐾𝑝 From equation (61) and equation (62), we have 𝑝𝐶𝑐 𝑝𝐷𝑑 (63) 𝐾𝑝 = 𝑝𝐴𝑎 𝑝𝐵𝑏 Which is again the modern statement of “law of mass action” but in terms of partial pressures. Buy the complete book with TOC navigation, Copyright © Mandeep Dalal high resolution images and no watermark. 296 A Textbook of Physical Chemistry – Volume I Other forms of equation (63) can also be written depending upon the reactants and products involved. If the chemical potentials of the reactants and products are in mole fractions (xi) i.e. 𝜇𝑖 = 𝜇𝑖0 + 𝑅𝑇 ln 𝑥𝑖 (64) Then equation (63) takes the form 𝑥𝐶𝑐 𝑥𝐷𝑑 (65) 𝐾𝑥 = 𝑥𝐴𝑎 𝑥𝐵𝑏 Similarly, If the chemical potentials of the reactants and products are in molar concentrations (ci) i.e. 𝜇𝑖 = 𝜇𝑖0 + 𝑅𝑇 ln 𝑐𝑖 (66) Then equation (63) takes the form [𝐶]𝑐 [𝐷]𝑑 (67) 𝐾𝑐 = [𝐴]𝑎 [𝐵]𝑏 Which is the popular form of “law of mass action”. Copyright © Mandeep Dalal  UNIT– I: Bioenergetics UNIT I: Bioenergetics:- Concept of free energy, endergonic and exergonic reaction, Relationship between free energy, enthalpy and entropy; Redox potential: Energy rich compounds; classification; biological significances of ATP and cyclic AMP  Bioenergetics  Defination - Bioenergetics means study of the transformation of energy in living organisms. - The goal of bioenergetics is to describe how living organisms acquire and transform energy in order to perform biological work. The study of metabolic pathways is thus essential to bioenergetics. - In a living organism, chemical bonds are broken and made as part of the exchange and transformation of energy. Energy is available for work (such as mechanical work) or for other processes (such as chemical synthesis and anabolic processes in growth), when weak bonds are broken and stronger bonds are made. The production of stronger bonds allows release of usable energy. - Adenosine triphosphate (ATP) is the main "energy currency" for organisms; the goal of metabolic and catabolic processes are to synthesize ATP from available starting materials (from the environment), and to break- down ATP (into adenosine diphosphate (ADP) and inorganic phosphate) by utilizing it in biological processes. - In a cell, the ratio of ATP to ADP concentrations is known as the "energy charge" of the cell. - A cell can use this energy charge to relay information about cellular needs; if there is more ATP than ADP available, the cell can use ATP to do work, but if there is more ADP than ATP available, the cell must synthesize ATP via oxidative phosphorylation. - Living organisms produce ATP from energy sources via oxidative phosphorylation. The terminal phosphate bonds of ATP are relatively weak compared with the stronger bonds formed when ATP is hydrolyzed (broken down by water) to adenosine diphosphate and inorganic phosphate. Here it is the thermodynamically favorable free energy of hydrolysis that results in energy release; the phosphoanhydride bond between the terminal phosphate group and the rest of the ATP molecule does not itself contain this energy. Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 1 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  Types of Bioenergetics Reactions 1. Exergonic Reaction - Exergonic implies the release of energy from a spontaneous chemical reaction without any concomitant utilization of energy. - The reactions are significant in terms of biology as these reactions have an ability to perform work and include most of the catabolic reactions in cellular respiration. - Most of these reactions involve the breaking of bonds during the formation of reaction intermediates as is evidently observed during respiratory pathways. The bonds that are created during the formation of metabolites are stronger than the cleaved bonds of the substrate. - The release of free energy, G, in an exergonic reaction (at constant pressure and temperature) is denoted as ΔG = Gproducts – Greactants < 0 2. Endergonic Reactions - Endergonic in turn is the opposite of exergonic in being non-spontaneous and requires an input of free energy. Most of the anabolic reactions like photosynthesis and DNA and protein synthesis are endergonic in nature. - The release of free energy, G, in an exergonic reaction (at constant pressure and temperature) is denoted as ΔG = Gproducts – Greactants  0 - 3. Activation Energy - Activation energy is the energy which must be available to a chemical system with potential reactants to result in a chemical reaction. Activation energy may also be defined as the minimum energy required starting a chemical reaction. Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 2 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  Examples of Major Bioenergetics Processes  Glycolysis is the process of breaking down glucose into pyruvate, producing net eight molecules of ATP (per 1 molecule of glucose) in the process. Pyruvate is one product of glycolysis, and can be shuttled into other metabolic pathways (gluconeogenesis, etc.) as needed by the cell. Additionally, glycolysis produces equivalents in the form of NADH (nicotinamide adenine dinucleotide), which will ultimately be used to donate electrons to the electron transport chain.  Gluconeogenesis is the opposite of glycolysis; when the cell's energy charge is low (the concentration of ADP is higher than that of ATP), the cell must synthesize glucose from carbon- containing biomolecules such as proteins, amino acids, fats, pyruvate, etc. For example, proteins can be broken down into amino acids, and these simpler carbon skeletons are used to build/ synthesize glucose.  The citric acid cycle is a process of cellular respiration in which acetyl coenzyme A, synthesized from pyruvate dehydrogenase, is first reacted with oxaloacetate to yield citrate. The remaining eight reactions produce other carbon- containing metabolites. These metabolites are successively oxidized, and the free energy of oxidation is conserved in the form of the reduced coenzymes FADH2 and NADH. These reduced electron carriers can then be re- oxidized when they transfer electrons to the electron transport chain.  Ketosis is a metabolic process whereby ketone bodies are used by the cell for energy (instead of using glucose). Cells often turn to ketosis as a source of energy when glucose levels are low; e.g. during starvation.  Oxidative phosphorylation and the electron transport chain is the process where reducing equivalents such as NADPH, FADH2 and NADH can be used to donate electrons to a series of redox reactions that take place in electron transport chain complexes. These redox reactions take place in enzyme complexes situated within the mitochondrial membrane. These redox reactions transfer electrons "down" the electron transport chain, which is coupled to the proton motive force. This difference in proton concentration between the mitochondrial matrix and inner membrane space is used to drive ATP synthesis via ATP synthase.  Photosynthesis, another major bioenergetic process, is the metabolic pathway used by plants in which solar energy is used to synthesize glucose from carbon dioxide and water. This reaction takes place in the chloroplast. After glucose is synthesized, the plant cell can undergo photophosphorylation to produce ATP. Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 3 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  Bioenergetics Relationship Between Free Energy, Enthalpy & Entropy - Every living cell and organism must perform work to stay alive, to grow and to reproduce. The ability to harvest energy from nutrients or photons of light and to channel it into biological work is the miracle of life. - 1st Law of Thermodynamics: The energy of the universe remains constant. - 2nd Law of Thermodynamics: All spontaneous processes increase the entropy of the universe. - The important state functions for the study of biological systems are:  The Gibbs free energy (G) which is equal to the total amount of energy capable of doing work during a process at constant temperature and pressure. o If ∆G is negative, then the process is spontaneous and termed exergonic. o If ∆G is positive, then the process is nonspontaneous and termed endergonic. o If ∆G is equal to zero, then the process has reached equilibrium.  The Enthalpy (H) which is the heat content of the system. Enthalpy is the amount of heat energy transferred (heat absorbed or emitted) in a chemical process under constant pressure. o When ∆H is negative the process produces heat and is termed exothermic. o When ∆H is positive the process absorbs heat and is termed endothermic.  The Entropy (S) is a quantitative expression of the degree of randomness or disorder of the system. Entropy measures the amount of heat dispersed or transferred during a chemical process. o When ∆S is positive then the disorder of the system has increased. o When ∆S is negative then the disorder of the system has decreased. - The conditions of biological systems are constant temperature and pressure. Under such conditions the relationships between the change in free energy, enthalpy and entropy can be described by the expression where T is the temperature of the system in Kelvin. ∆G = ∆H − T∆S [∆G = Gibbs Free Energy; ∆H = Change in Enthalpy; T = Temperature in K; ∆S = Change in Entropy] Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 4 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  Energy Rich Compounds - High energy phosphates act as energy currency of cell. - Three major sources of high energy phosphates taking part in energy conservation or energy capture. 1. Oxidative phosphorylation (or OXPHOS in short) - In metabolic pathway, cells use enzymes to oxidize nutrients, thereby releasing energy which is used to produce adenosine triphosphate (ATP). In most eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is probably so pervasive because it is a highly efficient way of releasing energy, compared to alternative fermentation processes such as anaerobic glycolysis. - The process that accounts for the high ATP yield is known as oxidative phosphorylation. - In glycolysis and the citric-acid cycle generate other products besides ATP and GTP, namely NADH and FADH2. These products are molecules that are oxidized (i.e., give up electrons) spontaneously. The body uses these reducing agents (NADH and FADH2) in an oxidation-reduction reaction 2. Glycolysis: - Cells use the glycolysis pathway to extract energy from sugars, mainly glucose, and store it in molecules of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). The end product of glycolysis is pyruvate, which can be used in other metabolic pathways to yield additional energy. - During glycolysis ATP molecules are used and formed in the following reactions (aerobic phase). - Reactions Catalyzed ATP used ATP formed - Stage I: - 1. Glucokinase (for phosphorylation) 1 - 2. Phosphofructokinase I (for phosphorylation) 1 Stage II: 3. Glyceraldehyde 3-phosphate dehydrogenase 6 (oxidation of 2 NADH in respiratory chain) 4. Phosphoglycerate kinase (substrate level phosphorylation) 2 Stage IV: 2 5. Pyruvate kinase (substrate level phosphorylation) Total 2 10 Net gain 08 - In the anaerobic phase oxidation of one glucose molecule produces 4 - 2 = 2 ATP. Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 5 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics 3. TCA Cycle - The citric acid cycle (CAC) – also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl- CoA derived from carbohydrates, fats, and proteins into carbon dioxide and chemical energy in the form of adenosine triphosphate (ATP). - If one molecule of the substrate is oxidized through NADH in the electron transport chain three molecules of ATP will be formed and through FADH2, two ATP molecules will be generated. As one molecule of glucose gives rise to two molecules of pyruvate by glycolysis, intermediates of citric acid cycle also result as two molecules.  Energy shuttles: i. NADH: An energy shuttle which delivers high energy electrons to the electron transport chain where they will eventually power the production of 2 to 3 ATP molecules. When this electron shuttle is not carrying high energy electrons, meaning it has been oxidized (lost its electrons), it is left with a positive charge and is called NAD+. ii. FADH2: Another energy shuttle that carries high energy electrons to the electron transport chain, where they will ultimately drive production of 1 to 2 ATP molecules. The oxidized form of FADH2 is FAD and happens just like in NADH. High energy molecules: iii. ATP: The basic energy currency of the cell. It’s a form of energy that cells can use right away. iv. GTP: Similar to ATP, GTP can be easily converted to ATP in the cell. Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 6 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics 4. Energy Released by Hydrolysis of Some Phosphate Compounds Energy Released Type Example (kcal/mol) acyl phosphate 1,3-bisphosphoglycerate (BPG) −11.8 acetyl phosphate −11.3 guanidine phosphates creatine phosphate −10.3 arginine phosphate −9.1 pyrophosphates PPi* → 2Pi −7.8 ATP → AMP + PPi −7.7 ATP → ADP + Pi −7.5 ADP → AMP + Pi −7.5 sugar phosphates glucose 1-phosphate −5.0 fructose 6-phosphate −3.8 AMP → adenosine + Pi −3.4 Glucose-6-phosphate −3.3 Glycerol-3-phosphate −2.2 *PPi is the pyrophosphate ion. Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 7 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  ADENOSINE TRIPHOSPHATE (ATP)  Adenosine-5'-triphosphate (ATP) is a multifunctional nucleotide used in cells as a coenzyme.  It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism.  It is produced by photophosphorylation and cellular respiration and used by enzymes and structural proteins in many cellular processes, including biosynthetic reactions, motility, and cell division.  One molecule of ATP contains three phosphate groups and it is produced by ATP synthase from inorganic phosphate and adenosine diphosphate (ADP) or adenosine monophosphate (AMP).  The structure of this molecule consists of a purine base (adenine) attached to the 1' carbon atom of a pentose sugar (ribose). Three phosphate groups are attached at the 5' carbon atom of the pentose sugar. It is the addition and removal of these phosphate groups that inter-convert ATP, ADP and AMP. When ATP is used in DNA synthesis, the ribose sugar is first converted to deoxyribose by ribonucleotide reductase.  The three main functions of ATP in cellular function are: 1. Transporting organic substances—such as sodium, calcium, potassium—through the cell membrane. 2. Synthesizing chemical compounds, such as protein and cholesterol. 3. Supplying energy for mechanical work, such as muscle contraction.  The standard amount of energy released from hydrolysis of ATP can be calculated from the changes in energy under non-natural (standard) conditions, then correcting to biological concentrations. The energy released by cleaving either a phosphate (Pi) or pyrophosphate (PPi) unit from ATP at standard state of 1 M are: ATP + H2O → ADP + Pi ΔG˚ = −30.5 kJ/mol (−7.3 kcal/mol) ATP + H2O → AMP + PPi ΔG˚ = −45.6 kJ/mol (−10.9 kcal/mol) These values can be used to calculate the change in energy under physiological conditions and the cellular ATP/ADP ratio (also known as the Energy Charge). This reaction is dependent on a number of factors, including overall ionic strength and the presence of alkaline earth metal ions such as Mg2+ and Ca2+. Under typical cellular conditions, ΔG is approximately −57 kJ/mol (−14 kcal/mol). Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 8 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  CYCLIC ADENOSINE MONOPHOSPHATE (cAMP, cyclic AMP or 3'-5'-cyclic adenosine monophosphate)  It is a second messenger important in many biological processes. cAMP is derived from adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway.  cAMP is synthesised from ATP by adenylyl cyclase located on the inner side of the plasma membrane. Adenylyl cyclase is activated by a range of signaling molecules through the activation of adenylyl cyclase stimulatory G (Gs)-protein-coupled receptors and inhibited by agonists of adenylyl cyclase inhibitory G (Gi)-protein-coupled receptors. Liver adenylyl cyclase responds more strongly to glucagon, and muscle adenylyl cyclase responds more strongly to adrenaline.  cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase.  Function: cAMP is a second messenger, used for intracellular signal transduction, such as transferring the effects of hormones like glucagon and adrenaline, which cannot pass through the cell membrane. It is involved in the activation of protein kinases and regulates the effects of adrenaline and glucagon. It also regulates the passage of Ca2+ through ion channels. cAMP and its associated kinases function in several biochemical processes, including the regulation of glycogen, sugar, and lipid metabolism by activating protein kinase Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 9 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  GUANOSINE TRIPHOSPHATE (GTP)  Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It can act as a substrate for both the synthesis of RNA during the transcription process and of DNA during DNA replication.  It also has the role of a source of energy or an activator of substrates in metabolic reactions, like that of ATP, but more specific. It is used as a source of energy for protein synthesis and gluconeogenesis.  GTP is essential to signal transduction, in particular with G-proteins, in second-messenger mechanisms where it is converted to Guanosine diphosphate (GDP) through the action of GTPases.  USES:  Energy transfer - GTP is involved in energy transfer within the cell. For instance, a GTP molecule is generated by one of the enzymes in the citric acid cycle. This is tantamount to the generation of one molecule of ATP, since GTP is readily converted to ATP with nucleoside-diphosphate kinase (NDK).  Genetic translation - During the elongation stage of translation, GTP is used as an energy source for the binding of a new amino- bound tRNA to the A site of the ribosome.  Mitochondrial function - The translocation of proteins into the mitochondrial matrix involves the interactions of both GTP and ATP.  Synthesis of AMP and GMP from IMP. Guanosine Triphosphate Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 10 GITAM (Deemed to be University) E-mail: [email protected]  UNIT– I: Bioenergetics  Cyclic Guanosine Monophosphate - Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). - cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface. - Synthesis: Guanylate cyclase (GC) catalyzes cGMP synthesis. This enzyme converts GTP to cGMP. Schematic representation of synthesis, degradation, and function of cGMP. The three targets of cGMP molecules are (i) cGMP dependent protein kinases, (ii) cGMP gated ion channels and (iii) cGMP-dependent phosphodiesterases. While phosphodiesterases are involved in the degradation of cGMP to GMP, the protein kinases and activation of ion channels are subsequently involved in various bacterial signaling pathways. GTP: Guanosine 5′-triphosphate; sGC: soluble guanylate cyclase; NO: nitric oxide; H-NOX: Heme-Nitric oxide/Oxygen domain; cGMP: cyclic guanosine 3′,5′-monophosphate; PDE: Phosphodiesterase; GMP: guanosine 3′,5′- monophosphate; ATP: adenosine 5′-triphosphate. - Effects  cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles leads to vasodilation and increased blood flow.  cGMP is a secondary messenger in phototransduction in the eye.  cGMP is involved in the regulation of some protein-dependent kinases. Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 202T)_B.Pharm-II Sem Page | 11 GITAM (Deemed to be University) E-mail: [email protected] View publication stats