2Start Your Engines Is a living organism an open or closed system? Explain your answer.
3Metabolism Metabolism in the living cell Miniature factory where thousands of reactions or energy conversions occurEnergyFree energyEnergy in Biological systemsATPEnzymesFunctionRegulation
4Explain the concept of energy coupling in the of biological system. Starter.Explain the concept ofenergy coupling in theof biological system.(hint: think ATP)
5Metabolism What is Metabolism The totality of an organisms chemical reactions.
6MetabolismEnergy Conversion is not 100%Metabolism transforms matter and energy, subject to the laws of thermodynamicsEnergy can be transferred andtransformed but NOT destroyed2. Every energy transformationIncreases the entropy in the universe.
7Metabolic Pathways Metabolism is Controlled Metabolism occurs in pathways sometimes with many steps.Begins w/ specific molecule, ends w/ productEach step catalyzed by specific enzymeEnzyme 1Enzyme 2Enzyme 3ABCDReaction 1Reaction 2Reaction 3Starting moleculeProduct
9Metabolism Anabolic pathways Build complicated molecules from simpler onesConsume energy
10Energy can be converted from one form to another On the platform, a diverhas more potential energy.Diving converts potentialenergy to kinetic energy.Climbing up converts kineticenergy of muscle movementto potential energy.In the water, a diver hasless potential energy.Figure 8.2KineticPotentialChemicalThermal
11Energy in a Biological System Energy conversionChemicalenergy
12The Second Law of Thermodynamics Spontaneous changes increase the entropy, or disorder, of the universeHeatco2H2O+Energy Conversion is not 100%
13Energy Living systems Increase entropy of the universe Use energy to maintain order50µmFigure 8.4
14Free-Energy Change, GDetermines if reaction occurs spontaneously
15∆Free energy= ∆(Enthalpy) – T∆(Entropy) Negative ∆G= Spontaneous Change in free energy, ∆G during a biological processRelated directly to the enthalpy (total energy of a system ∆H) change and the change in entropy∆G = ∆H – T∆S∆Free energy= ∆(Enthalpy) – T∆(Entropy)Negative ∆G= SpontaneousPositive ∆G = Requires energy
16(a) Exergonic reaction: energy released Net release of free E, spontaneousFigure 8.6ReactantsProductsEnergyProgress of the reactionAmount ofenergyreleased (∆G <0)Free energy(a) Exergonic reaction: energy released
17(b) Endergonic reaction: energy required Absorbs free E from surroundings, nonspontaneousFigure 8.6EnergyProductsAmount ofenergyreleased (∆G>0)ReactantsProgress of the reactionFree energy(b) Endergonic reaction: energy required
18Energy in a Biological Systems Maximum stability system 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 stableGreater work capacityLess free energy (lower G)More stableLess work capacityIn a spontaneously changeThe free energy of the system decreases (∆G<0)The system becomes more stableThe released free energy canbe harnessed to do work(a)(b)(c)Figure 8.5
19Metabolic pathways as systems: Closed System Reactions in a closed system eventually reach equilibrium∆G < 0∆G = 0
20Cells constant flow of materials in and out, do not reach equilibrium Open SystemCells constant flow of materials in and out, do not reach equilibrium∆G < 0
21Multi-Step Open System Analogy for cellular respiration∆G < 0Holy Exergonic ReactionsBatman!
22ATP Cellular Energy Currency (adenosine triphosphate)Cell’s Energy shuttle. ATP powers cellular work by coupling exergonic reactions to endergonic reactionsFigure 8.8OCH2HOHNCHCNH2AdenineRibosePhosphate groups-CH
23ATPE released from ATP when terminal phosphate bond is broken (hydrolysis)Figure 8.9PAdenosine triphosphate (ATP)H2O+EnergyInorganic phosphateAdenosine diphosphate (ADP)P i
24ATP Must look at total ∆G ATP hydrolysis coupled to other reactionsEndergonic reaction: ∆G is positive, reactionis not spontaneous∆G = +3.4 kcal/molGlu∆G = kcal/molATPH2O+NH3ADPNH2GlutamicacidAmmoniaGlutamineExergonic reaction: ∆ G is negative, reactionis spontaneousPCoupled reactions: Overall ∆G is negative;together, reactions are spontaneous∆G = –3.9 kcal/mol
25Cellular work powered by hydrolysis of ATP (c) Chemical work: ATP phosphorylates key reactantsPMembraneproteinMotor proteinP iProtein moved(a) Mechanical work: ATP phosphorylates motor proteinsATP(b) Transport work: ATP phosphorylates transport proteinsSolutetransportedGluNH3NH2+Reactants: Glutamic acidand ammoniaProduct (glutamine)madeADP
26Regeneration of ATP Energy from Food!! Catabolic pathways: ATP from ADP and phosphate (ATP Synthesis)ATP synthesis fromADP + P i requires energyATPADP + P iEnergy for cellular work(endergonic, energy-consuming processes)Energy from catabolism(exergonic, energy yieldingprocesses)ATP hydrolysis toADP + P i yields energyFigure 8.12
28Proteins, speed up metabolic reactions by lowering E barriers EnzymesProteins, speed up metabolic reactions by lowering E barriersCatalyst: speeds up a reaction w/o being consumed by the reactionProximity
29Enzymes Substrate Enzyme Reactant an enzyme acts on Binds to substrate, forming enzyme-substrate complexComplexSubstrateEnzyme
30Enzymes Lower the EA Barrier Activation energy, EA Initial amount of E needed to start a chemical reaction. Often in the form of heatProgress of the reactionProductsCourse ofreactionwithoutenzymeReactantswith enzymeEAEA withis lower∆G is unaffectedby enzymeFree energyFigure 8.15Even w/-∆G reactionmay be tooslow biologically
31How Enzymes Work Active site Region on enzyme where the substrate bindsFigure 8.16SubstateActive siteEnzyme(a)
32Induced fit of substrate substrate in positions that enhance catalysisFigure 8.16(b)Enzyme- substratecomplexCan be multipleactive sites
33Catalytic cycle of an enzyme Conformational changeSubstratesProductsEnzymeEnzyme-substratecomplex1 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 forsubstrate orientation,• stressing the substratesand stabilizing thetransition state,• providing a favorablemicroenvironment,• participating directly in thecatalytic reaction.4 Substrates areConverted intoProducts.5 Products areReleased.1 6 Active siteIs available fortwo new substrateMole.Figure 8.17
34(a) Optimal temperature for two enzymes Enzymes have optimal conditions in which they functionFigure 8.18Optimal temperature forenzyme of thermophilicRate of reaction204080100Temperature (Cº)(a) Optimal temperature for two enzymestypical human enzyme(heat-tolerant)bacteriaTemppH
37Enzyme Regulation: Competitive inhibitors Bind to active site, compete w/ 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 binding
38Enzyme regulation: Noncompetitive inhibitors Bind to another part of enzyme, changing functionFigure 8.19A noncompetitiveinhibitor binds to theenzyme away fromthe active site, alteringthe conformation ofthe enzyme so that itsactive site no longerfunctions.Noncompetitive inhibitor(c) Noncompetitive inhibition
39Enzyme Regulation: Allosteric Protein’s function at one site is affected by binding of a regulatory molecule at another siteStabilized inactive formAllosteric activater stabilizes active fromAllosteric enyzme with four subunitsActive site (one of four)Regulatory site (one of four)Active formActivatorStabilized active formAllosteric inactivater stabilizes inactive formInhibitorInactive formNon- functional active site(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
40Enzyme regulation: Cooperativity Cooperativity; allosteric regulation that amplifies enzyme activityFigure 8.20Binding of one substrate molecule to active 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.
41Enzyme Regulation: Feedback Inhibition End product of metabolic pathway shuts down pathwayActive site availableIsoleucine used up by cellFeedback inhibitionIsoleucine binds to allosteric siteActive site of enzyme 1 no longer binds threonine; pathway is switched offInitial substrate (threonine)Threonine in active siteEnzyme 1 (threonine deaminase)Intermediate AIntermediate BIntermediate CIntermediate DEnzyme 2Enzyme 3Enzyme 4Enzyme 5End product (isoleucine)Figure 8.21