3Organization of the Chemistry of Life into Metabolic Pathways A metabolic pathway begins with a specific molecule and ends with a productEach step is catalyzed by a specific enzymeCatabolic 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 catabolismAnabolic pathways consume energy to build complex molecules from simpler onesThe synthesis of protein from amino acids and photosynthesis are examples of anabolismBioenergetics is the study of how organisms manage their energy resourcesEnzyme 1Enzyme 2Enzyme 3ABCDReaction 1Reaction 2Reaction 3StartingmoleculeProduct
4Forms of EnergyKinetic Energy – energy of motion; heat (thermal energy) is kinetic energy associated with the random movement of atoms or moleculesPotential Energy – stored energy; the energy that matter possesses because of its location or structureChemical Energy – refers to the potential energy available for release in chemical reactions
5A diver has more potential energy on the platform than in the water. Fig. 8-2A diver has more potentialenergy on the platformthan in the water.Diving convertspotential energy tokinetic energy.Figure 8.2 Transformations between potential and kinetic energyClimbing up converts the kineticenergy of muscle movementto potential energy.A diver has less potentialenergy in the waterthan on the platform.
6Laws of Energy Transformation Thermodynamics – Study of the energy transformationsFirst Law of Thermodynamics – The energy of the universe is constant. Energy/Matter can be transferred and transformed, but it cannot be created of destroyedSecond Law of Thermodynamics – Every energy transfer of transformation increases the entropy (disorder/randomness) of the universe. Ordered forms of energy are at least partly converted to heat.CO2H2OHeatFigure 8.3 The two laws of thermodynamicsCO2+H2OChemicalenergy(a) First law of thermodynamics(b) Second law of thermodynamics
8Fig. 8-5 More free energy (higher G) Less stable Greater work capacity In a spontaneous changeThe free energy of the systemdecreases (∆G < 0)The system becomes morestableThe released free energy canbe harnessed to do workLess free energy (lower G)More stableLess work capacityFigure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change(a) Gravitational motion – Objectsmove spontaneously from ahigher altitude to a lower one(b) Diffusion – Moleculesin a drop of dye diffuseuntil the are randomlydispersed(c) Chemical reaction –In a cell, a sugarmolecule is brokendown into simplermolecules.
9Amount of energy released (∆G < 0) Fig. 8-6aReactantsAmount ofenergyreleased(∆G < 0)Free energyEnergyProductsFigure 8.6a Free energy changes (ΔG) in exergonic and endergonic reactionsProgress of the reactionExergonic reaction: proceedes with a net release of freeenergy and is spontaneous
10Amount of energy required (∆G > 0) Fig. 8-6bProductsAmount ofenergyrequired(∆G > 0)EnergyFree energyReactantsFigure 8.6b Free energy changes (ΔG) in exergonic and endergonic reactionsProgress of the reaction(b) Endergonic reaction: absorbs free energy from itssurrounding and is not spontaneous
11An isolated hydroelectric system. Water flowing downhill turns Fig. 8-7a∆G < 0∆G = 0Figure 8.7a Equilibrium and work in isolated and open systemsAn isolated hydroelectric system. Water flowing downhill turnsa turbines that drives a generator providing electricity to a lightbulb, but only until the system reaches equilibrium
12(b) An open hydroelectric system – Flowing water keeps Fig. 8-7b∆G < 0Figure 8.7b Equilibrium and work in isolated and open systems(b) An open hydroelectric system – Flowing water keepsdriving the generator because intake and outflow of waterkeep the system from reaching equilibrium.
13(c) A multistep open hydroelectric system – Cellular respiration Fig. 8-7c∆G < 0∆G < 0∆G < 0Figure 8.7c Equilibrium and work in isolated and open systems(c) A multistep open hydroelectric system – Cellular respirationis analogous to this system: Glucose is broken down in a seriesof exergonic reactions that power the work of the cell. Theproduct of each reaction becomes the reactant for the next, sono reaction reaches equilibrium.
15Adenine Phosphate groups Ribose Fig. 8-8 Figure 8.8 The structure of adenosine triphosphate (ATP)Ribose
16H2O P P P Adenosine triphosphate (ATP) P + P P + Energy Fig. 8-9PPPAdenosine triphosphate (ATP)H2OFigure 8.9 The hydrolysis of ATPP+PP+EnergyiInorganic phosphateAdenosine diphosphate (ADP)
17∆G = +3.4 kcal/mol Glutamic acid Ammonia Glutamine Fig. 8-10NH2NH3+∆G = +3.4 kcal/molGluGluGlutamicacidAmmoniaGlutamine(a) Endergonic reaction1ATP phosphorylatesglutamic acid,making the aminoacid less stable.P+ATP+ADPGluGluNH2P2Ammonia displacesthe phosphate group,forming glutamine.NH3++PiGluGluFigure 8.10 How ATP drives chemical work: Energy coupling using ATP hydrolysis(b) Coupled with ATP hydrolysis, an exergonic reaction(c) Overall free-energy change
19Membrane protein Solute Solute transported Vesicle Cytoskeletal track Fig. 8-11Membrane proteinATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant or proteinThe recipient molecule is now phosphorylatedPPiSoluteSolute transported(a) Transport work: ATP phosphorylatestransport proteinsADPATP+PiVesicleCytoskeletal trackFigure 8.11 How ATP drives transport and mechanical workATPMotor proteinProtein moved(b) Mechanical work: ATP binds noncovalentlyto motor proteins, then is hydrolyzed
20The Regeneration of ATP Fig. 8-12The 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 chemical potential energy temporarily stored in ATP drives most cellular workATPH2O+Figure 8.12 The ATP cycleEnergy for cellularwork (endergonic,energy-consumingprocesses)Energy fromcatabolism (exergonic,energy-releasingprocesses)PADP+i
22Sucrose (C12H22O11) Sucrase Glucose (C6H12O6) Fructose (C6H12O6) Fig. 8-13Sucrose (C12H22O11)SucraseFigure 8.13 Example of an enzyme-catalyzed reaction: hydrolysis of sucrose by sucraseGlucose (C6H12O6)Fructose (C6H12O6)
23Progress of the reaction Fig. 8-14ABCDTransition stateABEACDFree energyReactantsABFigure 8.14 Energy profile of an exergonic reaction∆G < OCDProductsProgress of the reaction
24Progress of the reaction Fig. 8-15Course ofreactionwithoutenzymeEAwithoutenzymeEA withenzymeis lowerReactantsFree energyCourse ofreactionwith enzyme∆G is unaffectedby enzymeFigure 8.15 The effect of an enzyme on activation energyProductsProgress of the reaction
25The active site can lower an EA barrier by Fig. 8-17Substrates enter active site; enzymechanges shape such that its active siteenfolds the substrates (induced fit).1Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.2SubstratesEnzyme-substratecomplexActive site can lower EAand speed up a reaction.3Activesite isavailablefor two newsubstratemolecules.6The active site can lower an EA barrier byOrienting substrates correctlyStraining substrate bondsProviding a favorable microenvironmentCovalently bonding to the substrateFigure 8.17 The active site and catalytic cycle of an enzymeEnzyme5Products arereleased.Substrates areconverted toproducts.4Products
26Substrate Active site Enzyme-substrate Enzyme complex Figure 8.16 Induced fit between an enzyme and its substrateEnzyme-substratecomplexEnzymeThe active site of the enzyme forms a groove onits surface.When the substrate enters the active site, it inducesa change in the shape of the protein, allowingmore weak bonds to form, causing the active site toEnfold the substrate and hold it in place.
27Optimal temperature for typical human enzyme Optimal temperature for Fig. 8-18Optimal temperature fortypical human enzymeOptimal temperature forenzyme of thermophilic(heat-tolerant)bacteriaEach enzyme has an optimal temperature in which it can functionEach enzyme has an optimal pH in which it can functionRate of reaction20406080100Temperature (ºC)(a) Optimal temperature for two enzymesOptimal pH for pepsin(stomach enzyme)Optimal pHfor trypsin(intestinalenzyme)Figure 8.18 Environmental factors affecting enzyme activityRate of reaction12345678910pH(b) Optimal pH for two enzymes
29Enzyme Inhibitors Substrate Active site Competitive inhibitor Enzyme Competitive 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 antibioticsSubstrateActive siteCompetitiveinhibitorFigure 8.19 Inhibition of enzyme activityEnzymeNoncompetitive inhibitor(a) Normal binding(b) Competitive inhibition(c) Noncompetitive inhibition
31Stabilized active form Fig. 8-20aAllosteric enzymewith four subunitsActive site(one of four)Regulatorysite (oneof four)ActivatorActive formStabilized active formOscillationFigure 8.20a Allosteric regulation of enzyme activityNon-functionalactivesiteInhibitorInactive formStabilized inactiveform(a) Allosteric activators and inhibitors
32(b) Cooperativity: another type of allosteric activation Fig. 8-20bCooperativity is a form of allosteric regulation that can amplify enzyme activityIn cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunitsSubstrateInactive formStabilized activeformFigure 8.20b Allosteric regulation of enzyme activity(b) Cooperativity: another type of allosteric activation
34Fig. 8-22 Initial substrate (threonine) Active site available in active siteEnzyme 1(threoninedeaminase)Isoleucineused up bycellIntermediate AFeedbackinhibitionEnzyme 2Active site ofenzyme 1 nolonger bindsthreonine;pathway isswitched off.Intermediate BEnzyme 3Intermediate CFigure 8.22 Feedback inhibition in isoleucine synthesisIsoleucinebinds toallostericsiteEnzyme 4Intermediate DEnzyme 5End product(isoleucine)
35Specific Localization of Enzymes Within the Cell Fig. 8-23MitochondriaSpecific 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 mitochondriaFigure 8.23 Organelles and structural order in metabolism1 µm
37Progress of the reaction Fig. 8-UN2Course ofreactionwithoutenzymeEAwithoutenzymeEA withenzymeis lowerReactantsFree energyCourse ofreactionwith enzyme∆G is unaffectedby enzymeProductsProgress of the reaction