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Visual Anatomy & Physiology First Edition Martini & Ober Chapter 22 (Sections 22.1-22.4) Metabolism & Cellular Respiration Lecture 8 Lecture Overview • Enzymes and control of metabolic reactions • Energy and metabolic reactions • Cellular respiration – – – – Overview ATP as the biological energy carrier Oxidation/Reduction Steps in Cellular Respiration • Glycolysis • The Citric Acid (Krebs) Cycle • The Electron Transport Chain • Relationship of anabolism to catabolism 2 Enzymes and Metabolic Reactions Enzymes – Biological catalysts • control rates of metabolic reactions • lower activation energy needed to start reactions • globular proteins with specific shapes • not consumed in chemical reactions • substrate specific • shape of active site determines which substrate(s) the enzyme can act on Figure from: Hole’s Human A&P, 12th edition, 2010 3 Enzymes Lower Activation Energy Enzymes lower the barriers that block chemical reactions, i.e., they lower the activation energy needed to begin energetically favorable reactions 5 Control of Metabolic Reactions Metabolic pathways • series of enzyme-controlled reactions leading to formation of a product • each new substrate is the product of the previous reaction Enzyme names commonly • reflect the substrate • have the suffix – ase • sucrase, lactase, protease, lipase, hydrolase, oxidase Factors that alter activity of enzymes • heat • radiation • substrate concentration • required cofactors • changes in pH 6 Cofactors and Coenzymes Cofactors • make some enzymes active • ions or coenzymes Coenzymes • complex organic molecules that act as cofactors (so coenzymes ARE cofactors) • vitamins • NAD+ Vitamins are essential organic substances that human cells cannot synthesize, i.e., they must come from the diet - required in very small amounts - examples - B vitamins: Thiamine (B1), niacin The protein parts of enzymes that need a nonprotein part (coenzymes, cofactors) to work are called apoenzymes 7 Overview of Cellular Metabolism Metabolism – All the chemical reactions that occur in an organism ETS KEEP THIS OVERALL SCHEME IN MIND AS WE GO INTO DETAILS!! Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 8 Overview of Glucose Breakdown 9 Figure from: Hole’s Human A&P, 12th edition, 2010 Overview of Catabolism Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011 11 A Closer Look at Mitochondria Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 (Impermeable to charged or polar molecules) Strategically placed in cell where ATP demand is high Concentration of enzymes in the matrix is so high that there is virtually no hydrating water. Enzyme-linked reactions and pathways are so crowded that normal rules of diffusion do not apply! 12 Carbohydrate Metabolism • Most cells generate ATP and other energyyielding compounds via the catabolism of carbohydrate (and fats) General Reaction sequence in carbohydrate catabolism C6H12O6 + 6 O2 6 CO2 + 6 H2O + ENERGY If the above reaction happened all at once, all the chemical energy contained in the carbohydrate would be DISSIPATED AS HEAT. How does the body harness the energy from carbohydrates? 13 Harnessing Energy - Stepwise Breakdown of Carbohydrates Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998 14 Energy for Metabolic Reactions Energy • ability to do work or change something (potential, kinetic) • heat, light, sound, electricity, mechanical energy, chemical energy • changed from one form to another, but NEVER destroyed (law of conservation of energy) • involved in all metabolic reactions Release of chemical energy • most metabolic processes depend on chemical energy • oxidation of glucose generates chemical energy • cellular respiration releases chemical energy slowly from molecules and makes it available for cellular use 15 Oxidation and Reduction Revisited Oxidation • gain of O2 • loss of e• loss of H (since a H carries an electron with it) • increase in oxidation number, e.g., Fe2+ -> Fe3+ Reduction • loss of O2 • gain of e• gain of H • decrease in oxidation number, e.g., Fe3+ -> Fe2+ Oxidation Is Loss of electrons; Reduction Is Gain of electrons “OIL RIG” 16 Energy of Organic Molecules • Carbohydrates like glucose store a great deal of chemical energy (as H·) • As carbohydrates (C6H12O6) are oxidized to CO2 they liberate their energy and lose electrons and H (H·) • But there must be molecules to accept these electrons, i.e., some molecules must be reduced. • In cellular respiration, O2 becomes the final electron (H·) acceptor and is reduced to H2O 17 Harnessing Energy from Carbohydrates General Reaction sequence in carbohydrate catabolism OXIDATION C6H12O6 + 6 O2 6 CO2 + 6 H2O + ENERGY REDUCTION Electrons (H·) “fall” in energy from organic molecules to oxygen during cellular respiration. That is, e- LOSE potential energy during this process and this energy is captured to make ATP However, electrons CANNOT be transferred directly from glucose to the electron transport chain. There are intermediates – activated carrier molecules 18 Activated Carrier Molecules Some activated carriers: ATP, NADH, FADH2, GTP, NADPH Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998 19 ATP – An Activated Carrier Molecule Figure from: Hole’s Human A&P, 12th edition, 2010 • each ATP molecule has three parts: • an adenine molecule These two components together are called a ? • a ribose molecule • three phosphate molecules in a chain • ATP carries its energy in the form or P (phosphate) • ATP is a readily interchangeable form of energy for cellular reactions (“common currency”) High-energy bonds 20 NAD(H) – An Activated Carrier Molecule NAD+ NAD (and NADP) are specialized to carry high-energy e- and H atoms A “packet” of energy = H· NADH + H+ NAD+ NADH These packets of energy will be passed to oxygen in the electron transport chain, and their energy used to drive the synthesis of ATP Important carriers of e- in catabolism: NADH, FADH2 Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998 21 Overview of Cellular Respiration Anaerobic Cellular respiration (aerobic) Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 22 Overview of Glucose Breakdown Figure from: Hole’s Human A&P, 12th edition, 2010 23 Overview of Glucose Breakdown Occurs in three major of reaction series… 1. Glycolysis (glucose to pyruvate; in cytoplasm) 2. Citric acid cycle (finishes oxidation begun in glycolysis; in the matrix of mitochondria) 3. Electron transport chain (uses e- transfer to make ATP; on inner membranes of mitochondria) Produces • carbon dioxide • water • ATP (chemical energy) • heat (energy has changed form from chemical) Includes • anaerobic reactions (without O2) - produce little ATP • aerobic reactions (requires O2) - produce most ATP 24 Glycolysis • series of ten reactions • breaks down glucose (6C) into 2 molecules of pyruvic acid (pyruvate) (3C) • occurs in cytosol • anaerobic phase of cellular respiration (that is, it can continue to work with OR without O2) • yields 2 ATP and 2 NADH molecules per glucose ADP + Pi Glucose (6C) ATP 2 Pyruvate (3C) NAD+ NADH 25 Overview of Glycolysis glucose (6C) → 2 pyruvate (3C) Figure from: Hole’s Human A&P, 12th edition, 2010 Products of glycolysis - ATP - NADH - Pyruvate NOTE what happens with and without O2 being available… 26 Metabolism of Pyruvate Without O2 • process of forming lactate from glucose is anerobic glycolysis • important for regenerating NAD+ so glycolysis can continue to generate ATP for the cell O2 Pyruvic acid (pyruvate) Lactic acid (lactate) NADH + H+ NAD+ NAD+ NADH + H+ Glucose (6C) 2 Pyruvate (3C) ADP + Pi ATP 27 Overview of Aerobic Reactions Figure from: Hole’s Human A&P, 12th edition, 2010 If oxygen is available – • pyruvic acid is used to produce acetyl CoA • citric acid (Krebs) cycle begins • electron transport chain functions • carbon dioxide and water are formed • maximum of 36 molecules of ATP produced per glucose molecule 28 Citric Acid Cycle Figure from: Hole’s Human A&P, 12th edition, 2010 In mitochondria… What happens… - Acetyl CoA enters cycle - Citric Acid is converted to various intermediates - Several important products are produced in these interconversions of citric acid… • ATP is produced •NAD+ is reduced to NADH and FAD is reduced to FADH2 • CO2 produced 29 Source of e- for the Electron Transport Chain Figure from: Hole’s Human A&P, 12th edition, 2010 Notice the flow of electrons to the Electron Transport Chain 30 Electron Transport Chain • NADH and FADH2 carry electrons to the ETC • ETC series of electron carriers located in cristae of mitochondria • energy from electrons transferred to ATP synthase • ATP synthase catalyzes the oxidative phosphorylation of ADP to ATP • water is formed *Chemiosmosis Figure from: Hole’s Human A&P, 12th edition, 2010 31 Oxidative Phosphorylation Chemiosmosis, Chemiosmotic coupling, or Chemiosmotic phosphorylation Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 32 Summary of Cellular Respiration Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 33 Is This All the Metabolism There Is? Definitely NOT! Notice how many lines connect pyruvate and Acetyl CoA to the rest of metabolism 34 Intermediates of Metabolism Acetyl CoA (2C) and Pyruvate (3C) are important: Allow interconversion of different types of molecules so cell’s needs can be met Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011 35 Figure from: Hole’s Human A&P, 12th edition, 2010 Summary of Catabolism of Proteins, Carbohydrates, and Fats Acetyl CoA is a common intermediate in the breakdown of most fuels. Acetyl CoA can be generated by carbohydrates, fats, or amino acids Acetyl CoA can be converted into fatty acids 36 Pyruvate is a Key Junction in Metabolism Lipogenesis Lipolysis * Glycogenolysis Glycogenesis Pyruvate is used to synthesize amino acids and Acetyl CoA Pyruvate can also be used to synthesize glucose via gluconeogenesis. Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 37 Carbohydrate Storage Excess glucose can be • stored as glycogen by glycogenesis (liver and muscle cells) • stored as fat by lipogenesis • converted to amino acids 38 Figure from: Hole’s Human A&P, 12th edition, 2010 Terms to Know… -olysis breakdown of -genesis creation of -neo new • Glycolysis – metabolism of glucose to pyruvate • Gluconeogenesis – metabolism of pyruvate to glucose (making CHO from non-CHO source) • Glycogenesis – metabolism of glucose to glycogen • Glycogenolysis – metabolism of glycogen to glucose • Lipolysis – breakdown of triglyceride into glycerol and fatty acids • Lipogenesis – creation of new triglyceride (fat) 39 Review • Enzymes are biological catalysts – – – – – Highly specific for their substrate Lower activation energy needed to start a reaction Are not consumed during reaction May require cofactors/coenzymes Effectiveness is greatly affected by temperature, pH, and the presence of required cofactors • The goal of metabolism is to provide the cell with energy (catabolism) and materials for the manufacture of cellular components (anabolism) 40 Review • Cells derive energy mainly from carbon compounds like carbohydrates and fats – These substances contain a great deal of energy stored in their chemical bonds – This energy must be liberated in stepwise fashion – Activated carriers serve as intermediates to capture the energy liberated at each step • Energy is the ability to do work – May be potential or kinetic – Changes form – Is never destroyed (only converted to another form) 41 Review • Anabolism is intimately tied to catabolism – Energy derived from catabolism is used to drive anabolic reactions – Some molecules are important junctions between catabolism and anabolism – Acetyl CoA • Generated from pyruvate, fatty acids, and amino acids • Can be used to synthesize fatty acids and other molecules • CANNOT be used to generate pyruvate – Pyruvate • Can be synthesized from glucose and amino acids • can be used to synthesize amino acids, glucose and acetyl CoA – NOTE, however, that in humans fatty acids cannot be converted to glucose 44