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Chapter 8 An Introduction to Metabolism PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Overview: The Energy of Life • The living cell – Is a miniature factory where thousands of reactions occur – Converts energy in many ways Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Some organisms – Convert energy to light, as in bioluminescence Figure 8.1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Metabolism – Is the totality of an organism’s chemical reactions – Arises from interactions between molecules Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Organization of the Chemistry of Life into Metabolic Pathways • A metabolic pathway has many steps – That begin with a specific molecule and end with a product – That are each catalyzed by a specific enzyme Enzyme 1 A Enzyme 2 D C B Reaction 1 Enzyme 3 Reaction 2 Starting molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Reaction 3 Product • Catabolic pathways – Break down complex molecules into simpler compounds – Release energy (-G) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Anabolic pathways – Build complicated molecules from simpler ones – Consume energy (+ G) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Forms of Energy • Energy – Is the capacity to cause change – Exists in various forms, of which some can perform work Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Kinetic energy – Is the energy associated with motion • Potential energy – Is stored in the location of matter – Includes chemical energy stored in molecular structure Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Energy can be converted – From one form to another On the platform, a diver has more potential energy. Climbing up converts kinetic energy of muscle movement Figure 8.2 to potential energy. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Diving converts potential energy to kinetic energy. In the water, a diver has less potential energy. The First Law of Thermodynamics • According to the first law of thermodynamics – Energy can be transferred and transformed – Energy cannot be created or destroyed Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • An example of energy conversion Chemical energy Figure 8.3 (a) First law of thermodynamics: Energy can be transferred or transformed but Neither created nor destroyed. For example, the chemical (potential) energy in food will be converted to the kinetic energy of the cheetah’s movement in (b). Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Second Law of Thermodynamics – Every energy transfer makes universe more disordered = increases entropy – When energy is transferred – some lost as heat – Amount of useful energy decreases when energy is transferred Heat co2 + H2O Figure 8.3 (b) Second law of thermodynamics: Every energy transfer or transformation increases the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s surroundings in the form of heat and the small molecules that are the by-products of metabolism. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Problem: • Living organisms are highly ordered: decrease entropy. • For example, Living organisms take in disordered amino acids and order them in the form of proteins. • Question: Do living organisms violate the second law? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • NO • Living organisms also take in ordered forms (starch) and break them into smaller more disordered units (glucose) • Must consider organism and their environment • Living organisms – Maintain highly ordered structure at the expense of increased entropy of surroundings – Take in complex high energy molecules, extract energy, release simpler low energy molecules (CO2 and H20) and heat to environment Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Energy Exchanges • Free energy (∆G) = work that can be performed by cell when Temp & pressure are uniform • The change in free energy, ∆G during a biological process – Is related directly to the enthalpy change (∆H) and the change in entropy (∆S) ∆G = ∆H – T∆S ∆H = change in enthalpy = heat of reaction Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Free Energy, Stability, and Equilibrium • Organisms live at the expense of free energy • During a spontaneous change – ∆G is negative • During every energy exchange (∆H) some energy is available to do work (∆G) and some is lost to the system (T∆S) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • At maximum stability – The system is at equilibrium • More free energy (higher G) • Less stable • Greater work capacity In a spontaneously change • The free energy of the system decreases (∆G<0) • The system becomes more stable • The released free energy can be harnessed to do work . • Less free energy (lower G) • More stable • Less work capacity (a) Gravitational motion. Objects move spontaneously from a higher altitude to a lower one. Figure 8.5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings (b) Diffusion. Molecules in a drop of dye diffuse until they are randomly dispersed. (c) Chemical reaction. In a cell, a sugar molecule is broken down into simpler molecules. Exergonic and Endergonic Reactions in Metabolism • An exergonic reaction – Proceeds with a net release of free energy and is spontaneous Reactants Free energy Amount of energy released (∆G <0) Energy Products Progress of the reaction Figure 8.6 (a) Exergonic reaction: energy released Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Exergonic Reactions R E n e r g y P Time •Reactants have more energy •More ordered to less •Unstable to stable •Downhill reaction •Free energy released •∆G is negative •Spontaneous •Examples: – Cellular Respiration – Digestion Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • An endergonic reaction – Is one that absorbs free energy from its surroundings and is nonspontaneous Free energy Products Energy Reactants Progress of the reaction Figure 8.6 (b) Endergonic reaction: energy required Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Amount of energy released (∆G>0) Endergonic Reactions P E n e r g R y Time Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings •Products have more energy than reactants •Less ordered to more •Stable to unstable •Uphill reaction •Free energy absorbed from surroundings •∆G is positive •Examples: – Photosynthesis – Polymer synthesis Couple Reactions •Energy released from exergonic reaction drives endergonic reaction R E n e r g y P Time Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings •Exergonic reaction ∆G = maximum work that can be done •Endergonic reaction ∆G = minimum work needed to drive the reaction • Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions • A cell does three main kinds of work – Mechanical – Transport – Chemical Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings ATP • Adenosine triphosphate • Has unstable phosphate bonds Adenine Unstable high energy bonds Phosphate groups Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ribose (5-C sugar) The Structure and Hydrolysis of ATP • ATP (adenosine triphosphate) – Is the cell’s energy shuttle – Provides energy for cellular functions Adenine N O O -O O - O - O O C C N HC O O O NH2 - Phosphate groups Figure 8.8 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings N CH2 O H N H H H OH CH C OH Ribose • Energy is released from ATP – When the terminal phosphate bond is broken P P P Adenosine triphosphate (ATP) H2O P i + Figure 8.9 Inorganic phosphate P P Adenosine diphosphate (ADP) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Energy Production Exergonic Energy from catabolism ATP Endergonic Energy for cellular work ∆G= -7.3 kcal/mol ∆G= +7.3 kcal/mol ADP + Pi Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How Does ATP Work •Mechanical: •Chemical: – Beating cilia – Endergonic reactions – Muscular contraction – Polymerization – Movement •Transport: – Active transport – Pumps (H+ and Na+/K+) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Energy coupling – Is a key feature in the way cells manage their energy resources to do this work Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • ATP hydrolysis – CanEndergonic be coupled to other reactions reaction: ∆G is positive, reaction is not spontaneous NH2 Glu + Glutamic acid NH3 Glu Ammonia Glutamine ∆G = +3.4 kcal/mol Exergonic reaction: ∆ G is negative, reaction is spontaneous ATP + H2O ADP + Coupled reactions: Overall ∆G is negative; together, reactions are spontaneous Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings P ∆G = + 7.3 kcal/mol ∆G = –3.9 kcal/mol How ATP Performs Work • ATP drives endergonic reactions – By phosphorylation, transferring a phosphate to other molecules P ATP GLU GLU ∆G= -7.3 kcal/mol P NH2 NH3 GLU GLU Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings ∆G = +3.4 kcal/mol ∆G = –3.9 kcal/mol Overall Rxn is exergonic • The three types of cellular work – Are powered by the hydrolysis of ATP P i P Motor protein Protein moved (a) Mechanical work: ATP phosphorylates motor proteins Membrane protein ADP + ATP P P Solute P i Solute transported (b) Transport work: ATP phosphorylates transport proteins P Glu + NH3 Reactants: Glutamic acid and ammonia Figure 8.11 NH2 Glu + P i Product (glutamine) made (c) Chemical work: ATP phosphorylates key reactants Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings i The Regeneration of ATP • Catabolic pathways – Drive the regeneration of ATP from ADP and phosphate ATP hydrolysis to ADP + P i yields energy ATP synthesis from ADP + P i requires energy ATP Energy from catabolism (exergonic, energy yielding processes) Figure 8.12 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Energy for cellular work (endergonic, energyconsuming processes) ADP + P i • Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers • A catalyst – Is a chemical agent that speeds up a reaction without being consumed by the reaction Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • An enzyme – Is a catalytic protein Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Activation Barrier • Every chemical reaction between molecules – Involves both bond breaking and bond forming Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The hydrolysis – Is an example of a chemical reaction CH2OH CH2OH O O H H H H OH H HO O + CH2OH H Sucrase H2O OH H OH CH2OH O H H H OH H OH HO H OH CH2OH O HO H HO H CH2OH OH H Sucrose Glucose Fructose C12H22O11 C6H12O6 C6H12O6 Figure 8.13 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The activation energy, EA – Is the initial amount of energy needed to start a chemical reaction – Is often supplied in the form of heat from the surroundings in a system Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The energy profile for an exergonic reaction A B C D Free energy Transition state A B C D EA Reactants A B C D ∆G < O Products Progress of the reaction Figure 8.14 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How Enzymes Lower the EA Barrier • An enzyme catalyzes reactions – By lowering the EA barrier Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The effect of enzymes on reaction rate Course of reaction without enzyme EA without enzyme Free energy EA with enzyme is lower Reactants ∆G is unaffected by enzyme Course of reaction with enzyme Products Progress of the reaction Figure 8.15 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Substrate Specificity of Enzymes • The substrate – Is the reactant an enzyme acts on • The enzyme – Binds to its substrate, forming an enzymesubstrate complex Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The active site – Is the region on the enzyme where the substrate binds Substate Active site Enzyme Figure 8.16 (a) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Induced fit of a substrate – Brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction Enzyme- substrate complex Figure 8.16 (b) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Catalysis in the Enzyme’s Active Site • In an enzymatic reaction – The substrate binds to the active site Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The catalytic cycle of an enzyme 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). Substrates Enzyme-substrate complex 6 Active site Is available for two new substrate Mole. Enzyme 5 Products are Released. Figure 8.17 Products Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site (and R groups of its amino acids) can lower EA and speed up a reaction by • acting as a template for substrate orientation, • stressing the substrates and stabilizing the transition state, • providing a favorable microenvironment, • participating directly in the catalytic reaction. 4 Substrates are Converted into Products. • The active site can lower an EA barrier by – Orienting substrates correctly – Straining substrate bonds – Providing a favorable microenvironment – Covalently bonding to the substrate Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Effects of Local Conditions on Enzyme Activity • The activity of an enzyme – Is affected by general environmental factors Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Effects of Temperature and pH • Each enzyme – Has an optimal temperature in which it can function Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic Rate of reaction (heat-tolerant) bacteria 0 20 40 Temperature (Cº) (a) Optimal temperature for two enzymes Figure 8.18 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 80 100 – Has an optimal pH in which it can function Optimal pH for pepsin (stomach enzyme) Rate of reaction Optimal pH for trypsin (intestinal enzyme) 3 4 0 2 1 (b) Optimal pH for two enzymes Figure 8.18 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 5 6 7 8 9 Cofactors • Cofactors – Are nonprotein enzyme helpers • Coenzymes – Are organic cofactors Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzyme Inhibitors • Competitive inhibitors – Bind to the active site of an enzyme, competing with the substrate A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding A competitive inhibitor mimics the substrate, competing for the active site. Figure 8.19 (b) Competitive inhibition Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Competitive inhibitor • Noncompetitive inhibitors – Bind to another part of an enzyme, changing the function A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor Figure 8.19 (c) Noncompetitive inhibition Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Concept 8.5: Regulation of enzyme activity helps control metabolism • A cell’s metabolic pathways – Must be tightly regulated Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allosteric Regulation of Enzymes • Allosteric regulation – Is the term used to describe any case in which a protein’s function at one site is affected by binding of a regulatory molecule at another site Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allosteric Activation and Inhibition • Many enzymes are allosterically regulated Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings – They change shape when regulatory molecules bind to specific sites, affecting function Allosteric enyzme with four subunits Regulatory site (one of four) Active site (one of four) Activator Active form Stabilized active form Oscillation Allosteric activater stabilizes active form NonInactive form Inhibitor functional active site Figure 8.20 Allosteric activater stabilizes active from Stabilized inactive form (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Cooperativity – Is a form of allosteric regulation that can amplify enzyme activity Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation. Substrate Inactive form Figure 8.20 Stabilized active form (b) Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Feedback Inhibition • In feedback inhibition – The end product of a metabolic pathway shuts down the pathway Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Feedback inhibition Active site available Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Isoleucine used up by cell Intermediate A Feedback inhibition Active site of enzyme 1 no longer binds threonine; pathway is switched off Enzyme 2 Intermediate B Enzyme 3 Intermediate C Isoleucine binds to allosteric site Enzyme 4 Intermediate D Enzyme 5 Figure 8.21 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings End product (isoleucine) Specific Localization of Enzymes Within the Cell • Within the cell, enzymes may be – Grouped into complexes – Incorporated into membranes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings – Contained inside organelles Mitochondria, sites of cellular respiraion Figure 8.22 1 µm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings