Bài giảng Biology - Chapter 8: An Introduction to Metabolism

Chapter 8An Introduction to MetabolismOverview: The Energy of Life The living cellIs a miniature factory where thousands of reactions occur Converts energy in many waysSome organisms Convert energy to light, as in bioluminescenceFigure 8.1Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamicsMetabolismIs the totality of an organism’s chemical reactionsArises from interactions between moleculesOrganization of the Chemistry of Life into Metabolic PathwaysA metabolic pathway has many stepsThat begin with a specific molecule and end with a productThat are each catalyzed by a specific enzymeEnzyme 1Enzyme 2Enzyme 3ABCDReaction 1Reaction 2Reaction 3StartingmoleculeProductCatabolic pathwaysBreak down complex molecules into simpler compoundsRelease energyAnabolic pathwaysBuild complicated molecules from simpler onesConsume energyForms of EnergyEnergyIs the capacity to cause changeExists in various forms, of which some can perform workKinetic energyIs the energy associated with motionPotential energyIs stored in the location of matterIncludes chemical energy stored in molecular structureEnergy can be convertedFrom one form to anotherOn the platform, a diverhas more potential energy.Diving converts potentialenergy to kinetic energy.Climbing up converts kineticenergy of muscle movement to potential energy.In the water, a diver has less potential energy.Figure 8.2The Laws of Energy TransformationThermodynamicsIs the study of energy transformationsThe First Law of ThermodynamicsAccording to the first law of thermodynamicsEnergy can be transferred and transformedEnergy cannot be created or destroyedAn example of energy conversion Figure 8.3 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).(a)ChemicalenergyThe Second Law of ThermodynamicsAccording to the second law of thermodynamicsSpontaneous changes that do not require outside energy increase the entropy, or disorder, of the universeFigure 8.3 Second law of thermodynamics: Every energy transfer or transformation increasesthe disorder (entropy) of the universe. For example, disorder is added to the cheetah’ssurroundings in the form of heat and the small molecules that are the by-productsof metabolism.(b)Heatco2H2O+Biological Order and DisorderLiving systemsIncrease the entropy of the universeUse energy to maintain order50µmFigure 8.4Concept 8.2: The free-energy change of a reaction tells us whether the reaction occurs spontaneouslyFree-Energy Change, GA living system’s free energyIs energy that can do work under cellular conditionsThe change in free energy, ∆G during a biological processIs related directly to the enthalpy change (∆H) and the change in entropy∆G = ∆H – T∆SFree Energy, Stability, and EquilibriumOrganisms live at the expense of free energyDuring a spontaneous changeFree energy decreases and the stability of a system increasesAt maximum stabilityThe system is at equilibriumChemical reaction. In a cell, a sugar molecule is broken down into simpler molecules. .Diffusion. Molecules in a drop of dye diffuse until they are randomly dispersed.Gravitational motion. Objectsmove spontaneously from ahigher altitude to a lower one. More free energy (higher G) Less stable Greater work capacity Less free energy (lower G) More stable Less work capacity In a spontaneously change The free energy of the system  decreases (∆G0)ReactantsProgress of the reactionFree energy(b) Endergonic reaction: energy requiredEquilibrium and MetabolismReactions in a closed systemEventually reach equilibriumFigure 8.7 A(a) A closed hydroelectric system. Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium.∆G < 0∆G = 0Cells in our bodyExperience a constant flow of materials in and out, preventing metabolic pathways from reaching equilibriumFigure 8.7 (b) An open hydroelectric  system. Flowing water keeps driving the generator  because intake and outflow  of water keep the system  from reaching equlibrium.∆G < 0An analogy for cellular respirationFigure 8.7 (c) A multistep open hydroelectric system. Cellular respiration is  analogous to this system: Glucoce is brocken down in a series of exergonic reactions that power the work of the cell. The product of each reaction becomes the reactant for the next, so no reaction  reaches equilibrium.∆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 workMechanicalTransportChemicalEnergy couplingIs a key feature in the way cells manage their energy resources to do this workThe Structure and Hydrolysis of ATPATP (adenosine triphosphate)Is the cell’s energy shuttleProvides energy for cellular functionsFigure 8.8 OOOOCH2HOHOHHNHHONCHCNCCNNH2AdenineRibosePhosphate groupsOOOOOO----CHEnergy is released from ATPWhen the terminal phosphate bond is brokenFigure 8.9 PAdenosine triphosphate (ATP)H2O+EnergyInorganic phosphateAdenosine diphosphate (ADP)PPPPP iATP hydrolysisCan be coupled to other reactionsEndergonic reaction: ∆G is positive, reaction is not spontaneous ∆G = +3.4 kcal/molGluGlu∆G = + 7.3 kcal/molATPH2O++NH3ADP+NH2GlutamicacidAmmoniaGlutamineExergonic reaction: ∆ G is negative, reaction is spontaneous PCoupled reactions: Overall ∆G is negative; together, reactions are spontaneous ∆G = –3.9 kcal/molFigure 8.10 How ATP Performs WorkATP drives endergonic reactionsBy phosphorylation, transferring a phosphate to other moleculesThe three types of cellular workAre powered by the hydrolysis of ATP(c) Chemical work: ATP phosphorylates key reactantsPMembraneprotein Motor proteinP iProtein moved(a) Mechanical work: ATP phosphorylates motor proteinsATP(b) Transport work: ATP phosphorylates transport proteinsSolutePP itransportedSoluteGluGluNH3NH2P iP i++Reactants: Glutamic acid and ammoniaProduct (glutamine)madeADP+PFigure 8.11 The Regeneration of ATPCatabolic pathwaysDrive the regeneration of ATP from ADP and phosphateATP synthesis from ADP + P i requires energyATPADP + P iEnergy for cellular work(endergonic, energy-consuming processes)Energy from catabolism(exergonic, energy yieldingprocesses)ATP hydrolysis to ADP + P i yields energyFigure 8.12 Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriersA catalystIs a chemical agent that speeds up a reaction without being consumed by the reactionAn enzymeIs a catalytic proteinThe Activation BarrierEvery chemical reaction between moleculesInvolves both bond breaking and bond formingThe hydrolysisIs an example of a chemical reactionFigure 8.13H2OHHHHHOOHOHOHOOOOOHHHHHHHCH2OHCH2OHOHCH2OHSucraseHOHOOHOHCH2OHHCH2OHHCH2OHHOSucroseGlucoseFructoseC12H22O11C6H12O6C6H12O6+HOHHThe activation energy, EAIs the initial amount of energy needed to start a chemical reactionIs often supplied in the form of heat from the surroundings in a systemThe energy profile for an exergonic reactionFree energyProgress of the reaction∆G < OEAFigure 8.14ABCDReactantsACDBTransition stateABCDProductsHow Enzymes Lower the EA BarrierAn enzyme catalyzes reactionsBy lowering the EA barrierThe effect of enzymes on reaction rateProgress of the reactionProductsCourse of reaction without enzymeReactantsCourse of reaction with enzymeEAwithoutenzymeEA with enzymeis lower∆G is unaffected by enzymeFree energyFigure 8.15Substrate Specificity of EnzymesThe substrateIs the reactant an enzyme acts onThe enzymeBinds to its substrate, forming an enzyme-substrate complexThe active siteIs the region on the enzyme where the substrate bindsFigure 8.16 SubstateActive siteEnzyme(a)Induced fit of a substrateBrings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reactionFigure 8.16 (b)Enzyme- substratecomplexCatalysis in the Enzyme’s Active SiteIn an enzymatic reactionThe substrate binds to the active siteThe catalytic cycle of an enzymeSubstratesProductsEnzymeEnzyme-substratecomplex 1 Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit). 2 Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.3 Active site (and R groups ofits amino acids) can lower EAand 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 intoProducts.5 Products areReleased.6 Active siteIs available fortwo new substrateMole.Figure 8.17The active site can lower an EA barrier byOrienting substrates correctlyStraining substrate bondsProviding a favorable microenvironmentCovalently bonding to the substrateEffects of Local Conditions on Enzyme ActivityThe activity of an enzymeIs affected by general environmental factorsEffects of Temperature and pHEach enzymeHas an optimal temperature in which it can functionFigure 8.18 Optimal temperature for enzyme of thermophilicRate of reaction0204080100Temperature (Cº)(a) Optimal temperature for two enzymesOptimal temperature fortypical human enzyme(heat-tolerant) bacteriaHas an optimal pH in which it can functionFigure 8.18 Rate of reaction(b) Optimal pH for two enzymesOptimal pH for pepsin (stomach enzyme)Optimal pHfor trypsin(intestinalenzyme)1023456789CofactorsCofactorsAre nonprotein enzyme helpersCoenzymesAre organic cofactorsEnzyme InhibitorsCompetitive inhibitorsBind to the active site of an enzyme, competing with the substrateFigure 8.19 (b) Competitive inhibitionA competitiveinhibitor mimics thesubstrate, competingfor the active site.CompetitiveinhibitorA substrate canbind normally to theactive site of anenzyme.SubstrateActive siteEnzyme (a) Normal bindingNoncompetitive inhibitorsBind to another part of an enzyme, changing the functionFigure 8.19 A noncompetitiveinhibitor binds to theenzyme away fromthe active site, alteringthe conformation ofthe enzyme so that itsactive site no longerfunctions.Noncompetitive inhibitor(c) Noncompetitive inhibitionConcept 8.5: Regulation of enzyme activity helps control metabolismA cell’s metabolic pathwaysMust be tightly regulatedAllosteric Regulation of EnzymesAllosteric regulationIs 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 siteAllosteric Activation and InhibitionMany enzymes are allosterically regulatedThey change shape when regulatory molecules bind to specific sites, affecting functionStabilized inactiveformAllosteric activaterstabilizes active fromAllosteric enyzmewith four subunitsActive site(one of four)Regulatorysite (oneof four)Active formActivatorStabilized active formAllosteric activaterstabilizes active formInhibitorInactive formNon-functionalactivesite(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.OscillationFigure 8.20 CooperativityIs a form of allosteric regulation that can amplify enzyme activityFigure 8.20 Binding of one substrate molecule toactive site of one subunit locks all subunits in active conformation.SubstrateInactive formStabilized 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. Feedback InhibitionIn feedback inhibitionThe end product of a metabolic pathway shuts down the pathwayFeedback inhibitionActive siteavailableIsoleucineused up bycellFeedbackinhibitionIsoleucine binds to allosteric siteActive site of enzyme 1 no longer binds threonine;pathway is switched offInitial substrate(threonine)Threoninein active siteEnzyme 1(threoninedeaminase)Intermediate AIntermediate BIntermediate CIntermediate DEnzyme 2Enzyme 3Enzyme 4Enzyme 5End product(isoleucine)Figure 8.21Specific Localization of Enzymes Within the CellWithin the cell, enzymes may beGrouped into complexesIncorporated into membranesContained inside organelles1 µmMitochondria,sites of cellular respiraionFigure 8.22