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and Energy Cellular Metabolism Chapter 4 Human Physiology Spring '09 1 Properties of Living Organisms Have highly organized, complex structure Acquire, transform, store, and use energy Sense and respond to internal and external environments Maintain homeostasis through internal control systems with feedback Store, use and transmit information Reproduce, develop, grow and die Have emergent properties that cannot be predicted from the simple sum of the parts Species evolve Human Physiology Spring '09 2 Properties Living organisms are highly organized and complex entities. Even a one-celled bacterium, although it appears simple under a microscope, has incredible complexity at the chemical level of organization. It uses intricately interconnected biochemical actions to acquire, transform, store, and use energy and information. It senses and responds to changes in its internal and external environments so that it can maintain homeostasis. It reproduces, develops, grows, and dies, and over time, its species evolves. Human Physiology Spring '09 3 Energy is Essential Energy is essential for these processes we associate with living things. Without energy for growth, repair, and maintenance of the internal environment, a cell is like a ghost town filled with buildings that are slowly crumbling into ruin. Cells need energy to import raw materials, make new molecules, and repair or recycle aging parts. The ability of cells to extract energy from the external environment and use that energy to maintain themselves as organized, functioning units is one of their most outstanding characteristics. Human Physiology Spring '09 4 Energy is Used to Perform Work All living organisms obtain, store, and use energy to fuel their activities. Energy can be defined as the capacity to do work. In biological systems the word work can mean one of three specific things Chemical work Transport work Mechanical work Human Physiology Spring '09 5 Chemical Work Chemical work: the making and breaking of chemical bonds, enables cells and organisms to grow, maintain a suitable internal environment, and store information needed for reproduction and other activities. Forming the chemical bonds of a protein the body will use for wound repair is an example of chemical work. Living organisms are characterized by their ability to extract energy from the environment and use it to support life processes. In a chemical reaction, a substance becomes a different substance, usually by the breaking and/or making of covalent bonds. A reaction begins with one or more molecules called reactants and ends with one or more molecules called products. The purpose of chemical reactions in cells is either to transfer energy from one molecule to another or to use energy stored in reactant molecules to do work. Human Physiology Spring '09 6 Transport and Mechanical Work Transport Work: enables cells to move ions, molecules, and larger particles through the cell membrane and through membranes of cell organelles. Transport work is particularly useful for creating concentration gradients, distributions of molecules in which the concentration is higher on one side of the membrane than on the other. For example a certain type of ER uses energy to import calcium ions from the cytosol. This ion transport creates a high calcium concentration inside the organelle and a low concentration of calcium in the cytosol. If calcium is then released back into the cytosol, it creates a calcium signal that causes the cell to perform some action, such as a muscle contraction. in animals is used for movement. At the cellular level, movement includes organelles moving around in a cell, cells changing shape, and cilia and flagella beating. At the microscopic level in animals, movement usually involves muscle contraction. Most mechanical work is mediated by motor proteins that make up certain intracellular fibers and filaments of the cytoskeleton. Mechanical work: Human Physiology Spring '09 7 Energy Comes in Two Forms: Kinetic and Potential We often think of energy in terms we deal with daily: thermal energy, electrical energy, mechanical energy. We speak of energy stored in chemical bonds. Kinetic Energy: Energy of motion. A ball rolling down a hill, cologne molecules spreading through the air, electric charge flowing through power lines, heat warming a frying pan, and molecules moving across biological membranes are all examples of bodies that have kinetic energy. Stored energy A ball sitting at the top of a hill has potential energy because it has the potential to start moving down the hill. A molecule positioned on the high concentration gradient stores potential energy because it has the potential energy to move down the gradient. In chemical bonds, potential energy is stored in the position of the electrons that form the bond. Potential Energy: Human Physiology Spring '09 8 Thermodynamics Is the Study of Energy Use The first law of thermodynamics, also known as the law of conservation of energy, states that the total amount of energy in the universe is constant. The universe is considered to be a closed system nothing enters and nothing leaves. Energy can be converted from one type to another, but the total amount of energy in a closed system never changes. The human body is not a closed system, however. As an open system, it exchanges materials and energy with its surroundings. Because our bodies cannot create energy, they import it from the outside in the form of food. Our bodies lose energy especially in the form of heat, to the environment. Energy that stays in the body can be changed from one type to another or can be used to do work. The second law of thermodynamics states that natural spontaneous processes move from a state of order to a condition of randomness or disorder, also known as entropy. Creating and maintaining order in an open system such as the body requires the input of energy. Human Physiology Spring '09 9 Energy is Transferred Between Molecules During Reactions To understand how chemical reactions transfer energy between molecules, we should answer two questions. How do reactions get started? Activation energy is the initial input of energy required to bring reactants into a position that allows them to react with one another. A reaction with low activation energy will proceed spontaneously when the reactants are brought together. You can demonstrate a spontaneous reaction by pouring a little vinegar onto some baking soda and watching the two react to form carbon dioxide. The products of a reaction will have either a lower free energy than the reactants or a higher free energy than the reactants. A change means that the reaction has either released or trapped energy. What happens to the free energy of the products and reactants during a reaction? Human Physiology Spring '09 10 Enzymes Enzymes are proteins that speed up the rate of chemical reactions. During these reactions, the enzyme molecules are not changed in any way, meaning they are biological catalysts. Without enzymes, most chemical reactions in a cell would go so slowly that the cell would be unable to live. A + B + enzyme------- C + D + enzyme this way of writing the reaction shows that the enzyme participates with reactants A and B but is unchanged at the end of the reaction. Most enzymes are large proteins with complex three dimensional shapes. Isozymes are enzymes that catalyze the same reaction but under different conditions or in different tissues. Isozymes have an important role in the diagnosis of certain medical conditions. For example, in the hours following a heart attack, damaged heart muscle cells release enzymes into the blood. One way to determine whether a persons chest pain was indeed due to a heart attack is to look for elevated levels of heart isozymes in the blood. Human Spring Physiology '09 11 Diagnostically Important Enzymes * Elevated blood levels of these enzymes are suggestive of the pathologies listed. Enzyme Related Disease Acid phosphatase Cancer of the prostate Alkaline phosphatase diseases of bone or liver Amylase Pancreatic disease Creatine kinase Myocardial infraction, muscle disease Glutamate dehydrogenase Liver disease Lactate dehydrogenase MI, liver disease, excess breakdown of RBC Human Physiology Spring '09 12 Metabolism Metabolism refers to all chemical reactions that take place in an organism. These reactions: Metabolism is often divided into catabolism, reactions that produce energy through the breakdown of large biomolecules, and anabolism, energy-utilizing reactions that result in the synthesis of large biomolecules The energy released from or stored in the chemical bonds of biomolecules during metabolism is commonly measured in kilocalories (kcal) A kilocalorie is the amount of energy needed to raise the temperature of 1 liter of water by 1 degree Celsius. Much of the energy released during catabolism is trapped in the high-energy phosphate bonds of ATP or in the high-energy electrons of NADH, FADH2 or NADPH. Anabolic reactions then transfer energy from these temporary carriers to the covalent bonds of biomolecules. Metabolism is a network of highly coordinated chemical reactions in which the activities taking place in a cell at any given moment are matched to the needs of the cell. Each step in a metabolic pathway is a different enzymatic reaction, and the reactions of a pathway proceed in sequence. Extract energy from nutrient biomolecules such as proteins, carbohydrates, and lipids Either synthesize or break down molecules Human Physiology Spring '09 13 Cells Regulate Their Metabolic Pathways 1. 2. 3. 4. 5. How do cells regulate the flow of molecules through their metabolic pathways? By By By By By controlling enzyme concentrations producing allosteric and covalent modulators using two different enzymes to catalyze reversible reactions isolating enzymes within intracellular organelles maintaining an optimum ratio of ATP to ADP14 Human Physiology Spring '09 14 Modulation of Enzymes Modulators alter the activity of a protein. A modulator is a factor that influences either protein binding or protein activity. Enzyme modulation is frequently controlled by hormones and other signals coming from outside the cell. This type of outside regulation is a key element in the integrated control of the bodys metabolism following a meal or during periods of fasting. Some metabolic pathways have their own built in form of modulation, called feedback inhibition. In this form of modulation, the end product of a pathway acts as an inhibitory modulator of the pathway. Inhibition of the enzyme slows down production until the cell can use it. Human Physiology Spring '09 15 Ratio of ATP to ADP The energy status of the cell is one final mechanism that can influence metabolic pathways. Through complex regulation, the ratio of ATP to ADP in the cell determines whether pathways that result in ATP synthesis are turned on or off. When ATP levels are high, production of ATP drops. When ATP levels are low, the cell sends substrates through pathways that result in more ATP synthesis. Human Physiology Spring '09 16 ATP Production Aerobic production of ATP from glucose commonly follows two pathways: glycolysis and the citric acid cycle Each of these pathways produces small amounts of ATP directly, but their most important contribution to ATP synthesis are high-energy electrons carried by NADH and FADH2 to the electron transport system in the mitochondria. The electron transport system transfers energy from electrons to the high-energy phosphate bond of ATP. At various points, the process produces CO2 which is a waste product and must be removed from the body, and H2O, which can be used by the cell. Carbohydrates enter glycolysis in the form of glucose. Lipids are broken down into glycerol and fatty acids which then enter the pathway at different points: glycerol feeds into glycolysis, and fatty acids are metabolized to acetyl CoA. Proteins are broken down into amino acids, which also enter at various points. Human Physiology Spring '09 17 Glycolysis Converts Glucose and Glycogen into Pyruvate During glycolysis, one molecule of glucose is converted by a series of enzymatically catalyzed reactions into two pyruvate molecules, producing a net release of energy. A portion of the energy released during glycolysis is used to phosphorylate ADP molecules, trapping the energy in ATP. Glycolysis does not require oxygen therefore serving as a common pathway for aerobic and anaerobic catabolism of glucose. The glycolysis pathway converts glucose, a six carbon sugar, into two three-carbon pyruvate molecules. Pyruvate is the branch point for aerobic and anaerobic metabolism of glucose. Aerobic glycolysis has a net energy yield of two ATP and two NADH. Human Physiology Spring '09 18 Anaerobic Metabolism Converts Pyruvate into Lactate Pyruvate is a branch point for the metabolic pathways. Depending on a cells needs and condition, pyruvate can be shuttled off into one of two pathways. If the cell contains adequate oxygen, pyruvate continues into the citric acid cycle. If the cell lacks sufficient oxygen for aerobic pathways ( a condition that may be caused by many factors, including strenuous exercise), pyruvate is converted into lactate with the assistance of the enzyme lactate dehydrogenase. The conversion of pyruvate to lactate changes one NADH back to NAD+ when a hydrogen atom and an electron are transferred to the lactate molecule. As a result, the net energy yield for the anaerobic metabolism of one glucose molecule is two ATP and no NADH. Human Physiology Spring '09 19 Pyruvate Enters the Citric Acid Cycle in Aerobic Metabolism If the cell has adequate oxygen for aerobic metabolism, the pyruvate molecules formed from glucose during glycolysis are transported into the mitochondria. Once in the mitochondrial matrix, pyruvate is converted into the key intermediate acetyl CoA. Its name suggests, this molecule has two parts: a two carbon acyl unit, derived from pyruvate and a coenzyme. Coenzyme A is made from the vitamin pantothenic acid. The synthesis of acetyl CoA from pyruvate and coenzyme A is an exergenic reaction that produces one NADH. During the reaction, one of the pyruvates three carbon atoms combines with oxygen and is released as CO2, leaving acetyl CoA with only two carbons. Acetyl CoA releases its two-carbon acyl into the citric acid cycle pathway (AKA Krebs cycle) The citric acid cycle makes a never ending circle, adding carbons from acetyl CoA with each turn of the cycle and producing ATP, high-energy electrons, and CO2. Human Physiology Spring '09 20 Clinical Focus Why do people with diabetes have elevated levels of blood glucose? Part of the answer lies with the disruption of glucose metabolism when insulin is absent or when cells do not respond to it. In a normal person, insulin promotes cellular uptake and metabolism of glucose by stimulating the appropriate enzymes. Glucose is absorbed from the digestive tract and goes through glycolysis to make ATP or is stored as glycogen. Fatty acids are stored as lipids, and amino acids are used to make proteins. In the absence of insulin, the enzymes associated with catabolic pathways are more active than those associated with anabolic pathways. In these overactive catabolic pathways, lipids undergo beta-oxidation, amino acids go through gluconeogenesis to become glucose, and glycogen stores are turned back into glucose. The increased production of glucose by cells coupled with the inability of many cells to absorb glucose from the blood creates the elevated blood sugar levels that are a hallmark of diabetes. Human Physiology Spring '09 21

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