Sinh học - Chapter 8: An introduction to metabolism

An Introduction to MetabolismChapter 8Overview: The Energy of LifeThe living cell is a miniature chemical factory where thousands of reactions occurThe cell extracts energy and applies energy to perform workSome organisms even convert energy to light, as in bioluminescence© 2011 Pearson Education, Inc.Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamicsMetabolism is the totality of an organism’s chemical reactionsMetabolism is an emergent property of life that arises from interactions between molecules within the cell© 2011 Pearson Education, Inc.Organization of the Chemistry of Life into Metabolic PathwaysA metabolic pathway begins with a specific molecule and ends with a productEach step is catalyzed by a specific enzyme© 2011 Pearson Education, Inc.Figure 8.UN01Enzyme 1Enzyme 2Enzyme 3Reaction 1Reaction 2Reaction 3ProductStartingmoleculeABCDCatabolic pathways release energy by breaking down complex molecules into simpler compoundsCellular respiration, the breakdown of glucose in the presence of oxygen, is an example of a pathway of catabolism© 2011 Pearson Education, Inc.Anabolic pathways consume energy to build complex molecules from simpler onesThe synthesis of protein from amino acids is an example of anabolismBioenergetics is the study of how organisms manage their energy resources© 2011 Pearson Education, Inc.Forms of EnergyEnergy is the capacity to cause changeEnergy exists in various forms, some of which can perform work© 2011 Pearson Education, Inc.Kinetic energy is energy associated with motionHeat (thermal energy) is kinetic energy associated with random movement of atoms or moleculesPotential energy is energy that matter possesses because of its location or structureChemical energy is potential energy available for release in a chemical reaction Energy can be converted from one form to another © 2011 Pearson Education, Inc.Figure 8.2A diver has more potentialenergy on the platformthan in the water.Diving convertspotential energy tokinetic energy.Climbing up converts the kineticenergy of muscle movementto potential energy.A diver has less potentialenergy in the waterthan on the platform.The Laws of Energy TransformationThermodynamics is the study of energy transformationsA isolated system, such as that approximated by liquid in a thermos, is isolated from its surroundingsIn an open system, energy and matter can be transferred between the system and its surroundingsOrganisms are open systems© 2011 Pearson Education, Inc.The First Law of ThermodynamicsAccording to the first law of thermodynamics, the energy of the universe is constantEnergy can be transferred and transformed, but it cannot be created or destroyedThe first law is also called the principle of conservation of energy© 2011 Pearson Education, Inc.The Second Law of ThermodynamicsDuring every energy transfer or transformation, some energy is unusable, and is often lost as heatAccording to the second law of thermodynamicsEvery energy transfer or transformation increases the entropy (disorder) of the universe© 2011 Pearson Education, Inc.Figure 8.3(a) First law of thermodynamics(b) Second law of thermodynamicsChemicalenergyHeatLiving cells unavoidably convert organized forms of energy to heatSpontaneous processes occur without energy input; they can happen quickly or slowlyFor a process to occur without energy input, it must increase the entropy of the universe© 2011 Pearson Education, Inc.Biological Order and DisorderCells create ordered structures from less ordered materialsOrganisms also replace ordered forms of matter and energy with less ordered formsEnergy flows into an ecosystem in the form of light and exits in the form of heat© 2011 Pearson Education, Inc.The evolution of more complex organisms does not violate the second law of thermodynamicsEntropy (disorder) may decrease in an organism, but the universe’s total entropy increases© 2011 Pearson Education, Inc.Concept 8.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneouslyBiologists want to know which reactions occur spontaneously and which require input of energyTo do so, they need to determine energy changes that occur in chemical reactions© 2011 Pearson Education, Inc.Free-Energy Change, GA living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell© 2011 Pearson Education, Inc.The change in free energy (∆G) during a process is related to the change in enthalpy, or change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin (T) ∆G = ∆H – T∆SOnly processes with a negative ∆G are spontaneousSpontaneous processes can be harnessed to perform work© 2011 Pearson Education, Inc.Free Energy, Stability, and EquilibriumFree energy is a measure of a system’s instability, its tendency to change to a more stable stateDuring a spontaneous change, free energy decreases and the stability of a system increasesEquilibrium is a state of maximum stabilityA process is spontaneous and can perform work only when it is moving toward equilibrium© 2011 Pearson Education, Inc.Figure 8.5• More free energy (higher G)• Less stable• Greater work capacityIn a spontaneous 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(b) Diffusion(c) Chemical reactionFree Energy and MetabolismThe concept of free energy can be applied to the chemistry of life’s processes© 2011 Pearson Education, Inc.Exergonic and Endergonic Reactions in MetabolismAn exergonic reaction proceeds with a net release of free energy and is spontaneousAn endergonic reaction absorbs free energy from its surroundings and is nonspontaneous© 2011 Pearson Education, Inc.Figure 8.6a(a) Exergonic reaction: energy released, spontaneousReactantsEnergyProductsProgress of the reactionAmount of energyreleased(G  0)Free energyFigure 8.6b(b) Endergonic reaction: energy required, nonspontaneousReactantsEnergyProductsAmount of energyrequired(G  0)Progress of the reactionFree energyEquilibrium and MetabolismReactions in a closed system eventually reach equilibrium and then do no workCells are not in equilibrium; they are open systems experiencing a constant flow of materialsA defining feature of life is that metabolism is never at equilibriumA catabolic pathway in a cell releases free energy in a series of reactionsClosed and open hydroelectric systems can serve as analogies© 2011 Pearson Education, Inc.Figure 8.7(a) An isolated hydroelectric system(b) An open hydro- electric system(c) A multistep open hydroelectric systemG  0G  0G  0G  0G  0G  0Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactionsA cell does three main kinds of workChemicalTransportMechanicalTo do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic oneMost energy coupling in cells is mediated by ATP© 2011 Pearson Education, Inc.The Structure and Hydrolysis of ATPATP (adenosine triphosphate) is the cell’s energy shuttleATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups© 2011 Pearson Education, Inc.Figure 8.8(a) The structure of ATPPhosphate groupsAdenineRiboseAdenosine triphosphate (ATP)EnergyInorganicphosphateAdenosine diphosphate (ADP)(b) The hydrolysis of ATPThe bonds between the phosphate groups of ATP’s tail can be broken by hydrolysisEnergy is released from ATP when the terminal phosphate bond is brokenThis release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves© 2011 Pearson Education, Inc.How the Hydrolysis of ATP Performs WorkThe three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATPIn the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reactionOverall, the coupled reactions are exergonic © 2011 Pearson Education, Inc.Figure 8.9GlutamicacidAmmoniaGlutamine(b)Conversionreactioncoupledwith ATPhydrolysisGlutamic acidconversionto glutamine(a)(c)Free-energychange forcoupledreactionGlutamicacidGlutaminePhosphorylatedintermediateGluNH3NH2GluGGlu = +3.4 kcal/molATPADPADPNH3GluGluPP iP iADPGluNH2GGlu = +3.4 kcal/molGluGluNH3NH2ATPGATP = 7.3 kcal/molGGlu = +3.4 kcal/mol+ GATP = 7.3 kcal/molNet G = 3.9 kcal/mol12Figure 8.10Transport proteinSoluteATPPP iP iADPP iADPATPATPSolute transportedVesicleCytoskeletal trackMotor proteinProtein andvesicle moved(b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed.(a) Transport work: ATP phosphorylates transport proteins.The Regeneration of ATPATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)The energy to phosphorylate ADP comes from catabolic reactions in the cellThe ATP cycle is a revolving door through which energy passes during its transfer from catabolic to anabolic pathways© 2011 Pearson Education, Inc.Figure 8.11Energy fromcatabolism (exergonic,energy-releasingprocesses)Energy for cellularwork (endergonic,energy-consumingprocesses)ATPADPP iH2OConcept 8.4: Enzymes speed up metabolic reactions by lowering energy barriersA catalyst is a chemical agent that speeds up a reaction without being consumed by the reactionAn enzyme is a catalytic proteinHydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction© 2011 Pearson Education, Inc.Figure 8.UN02SucraseSucrose(C12H22O11)Glucose(C6H12O6)Fructose(C6H12O6)The Activation Energy BarrierEvery chemical reaction between molecules involves bond breaking and bond formingThe initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (EA) Activation energy is often supplied in the form of thermal energy that the reactant molecules absorb from their surroundings© 2011 Pearson Education, Inc.Figure 8.12Transition stateReactantsProductsProgress of the reactionFree energyEAG  OABCDABCDABCDHow Enzymes Lower the EA BarrierEnzymes catalyze reactions by lowering the EA barrierEnzymes do not affect the change in free energy (∆G); instead, they hasten reactions that would occur eventually© 2011 Pearson Education, Inc.Figure 8.13Course ofreactionwithoutenzymeEAwithoutenzymeEA withenzymeis lowerCourse ofreactionwith enzymeReactantsProductsG is unaffectedby enzymeProgress of the reactionFree energySubstrate Specificity of EnzymesThe reactant that an enzyme acts on is called the enzyme’s substrate The enzyme binds to its substrate, forming an enzyme-substrate complexThe active site is the region on the enzyme where the substrate bindsInduced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction© 2011 Pearson Education, Inc.Figure 8.14SubstrateActive siteEnzymeEnzyme-substratecomplex(a)(b)Catalysis in the Enzyme’s Active SiteIn an enzymatic reaction, the substrate binds to the active site of the enzymeThe active site can lower an EA barrier byOrienting substrates correctlyStraining substrate bondsProviding a favorable microenvironmentCovalently bonding to the substrate© 2011 Pearson Education, Inc.Figure 8.15-3SubstratesSubstrates enter active site.Enzyme-substratecomplexEnzymeProducts Substrates are heldin active site by weakinteractions. Active site canlower EA and speedup a reaction.Activesite isavailablefor two newsubstratemolecules.Products arereleased. Substrates areconverted toproducts.123456Effects of Local Conditions on Enzyme ActivityAn enzyme’s activity can be affected byGeneral environmental factors, such as temperature and pHChemicals that specifically influence the enzyme© 2011 Pearson Education, Inc.Effects of Temperature and pHEach enzyme has an optimal temperature in which it can functionEach enzyme has an optimal pH in which it can functionOptimal conditions favor the most active shape for the enzyme molecule© 2011 Pearson Education, Inc.Figure 8.16Optimal temperature fortypical human enzyme (37°C)Optimal temperature forenzyme of thermophilic(heat-tolerant)bacteria (77°C)Temperature (°C)(a) Optimal temperature for two enzymesRate of reactionRate of reaction120100806040200012345678910pH(b) Optimal pH for two enzymesOptimal pH for pepsin(stomachenzyme)Optimal pH for trypsin(intestinalenzyme)CofactorsCofactors are nonprotein enzyme helpersCofactors may be inorganic (such as a metal in ionic form) or organicAn organic cofactor is called a coenzymeCoenzymes include vitamins© 2011 Pearson Education, Inc.Enzyme InhibitorsCompetitive inhibitors bind to the active site of an enzyme, competing with the substrateNoncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effectiveExamples of inhibitors include toxins, poisons, pesticides, and antibiotics© 2011 Pearson Education, Inc.Figure 8.17(a) Normal binding(b) Competitive inhibition(c) Noncompetitive inhibitionSubstrateActivesiteEnzymeCompetitiveinhibitorNoncompetitiveinhibitorConcept 8.5: Regulation of enzyme activity helps control metabolismChemical chaos would result if a cell’s metabolic pathways were not tightly regulatedA cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes© 2011 Pearson Education, Inc.Allosteric Regulation of EnzymesAllosteric regulation may either inhibit or stimulate an enzyme’s activityAllosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site© 2011 Pearson Education, Inc.Allosteric Activation and InhibitionMost allosterically regulated enzymes are made from polypeptide subunitsEach enzyme has active and inactive formsThe binding of an activator stabilizes the active form of the enzymeThe binding of an inhibitor stabilizes the inactive form of the enzyme© 2011 Pearson Education, Inc.Figure 8.19aRegulatory site (one of four)(a) Allosteric activators and inhibitorsAllosteric enzymewith four subunitsActive site(one of four)Active formActivatorStabilized active formOscillationNonfunctionalactive siteInactive formInhibitorStabilized inactive formFigure 8.19bInactive formSubstrateStabilized activeform(b) Cooperativity: another type of allosteric activationCooperativity is a form of allosteric regulation that can amplify enzyme activityOne substrate molecule primes an enzyme to act on additional substrate molecules more readilyCooperativity is allosteric because binding by a substrate to one active site affects catalysis in a different active site© 2011 Pearson Education, Inc.Feedback InhibitionIn feedback inhibition, the end product of a metabolic pathway shuts down the pathwayFeedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed© 2011 Pearson Education, Inc.Figure 8.21Active siteavailableIsoleucineused up bycellFeedbackinhibitionActive site ofenzyme 1 isno longer ableto catalyze theconversionof threonine tointermediate A;pathway isswitched off.Isoleucinebinds toallostericsite.Initial substrate(threonine)Threoninein active siteEnzyme 1(threoninedeaminase)Intermediate AIntermediate BIntermediate CIntermediate DEnzyme 2Enzyme 3Enzyme 4Enzyme 5End product(isoleucine)Specific Localization of Enzymes Within the CellStructures within the cell help bring order to metabolic pathwaysSome enzymes act as structural components of membranesIn eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria© 2011 Pearson Education, Inc.Figure 8.22MitochondriaThe matrix containsenzymes in solution thatare involved in one stageof cellular respiration.Enzymes for anotherstage of cellularrespiration areembedded in theinner membrane.1 mFigure 8.UN04Figure 8.UN05Figure 8.UN06