08 Lecture Presentation

Overview: The Energy of LifeThe living cell is a miniature chemical factory where thousands of reactions occur.The cell extracts energy and applies energy to perform work.Some organisms even convert energy to light, as in bioluminescence. Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

What causes the bioluminescence in these fungi?

An organisms metabolism transforms matter and energy, subject to the laws of thermodynamicsMetabolism is ALL / the totality of an organisms chemical reactions.Metabolism is an emergent property of life that arises from interactions between molecules within the cell.Metabolism has two basic subdivisions: Anabolism = building / synthesisCatabolism = breaking downCopyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Organization of the Chemistry of Life into Metabolic PathwaysA metabolic pathway begins with a specific molecule / substrate and ends with a product.Each step is catalyzed by a specific enzyme in a specific sequence.Metabolic pathways are regulated by various mechanisms.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Metabolic Pathways are organized into Specific SequencesEnzyme 1Enzyme 2Enzyme 3DCBAReaction 1Reaction 3Reaction 2StartingmoleculeProduct

Catabolic pathways will release energy by breaking down complex molecules into simpler compounds.Cellular respiration, the breakdown of glucose in the presence of oxygen, is an example of a pathway of catabolism.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Anabolic pathways consume / use energy to build complex molecules from simpler ones.The synthesis of protein from amino acids is an example of anabolism.

Bioenergetics is the study of how organisms manage their energy resources.

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Forms of EnergyEnergy is the capacity to cause change. Energy is the ability to do work.Energy exists in various forms, some of which can perform work.Energy can be converted from one form to another. The Laws of Thermodynamics govern all energy transformations.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Kinetic energy is energy associated with motion.Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules.Potential energy is energy that matter possesses because of its location or structure.Chemical energy is potential energy available for release in a chemical reaction.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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.Diving convertspotential energy tokinetic energy.A diver has more potentialenergy on the platformthan in the water.

The Laws of Energy Transformation: ThermodynamicsA closed system, such as that approximated by liquid in a thermos, is isolated from its surroundings.In an open system, energy and matter can be transferred between the system and its surroundings.Organisms are open systems, and they perform energy transformations to grow and survive.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The First Law of ThermodynamicsThe first law of thermodynamics: the energy of the universe is a constant quantity: Energy can be transferred and transformed, but it cannot be created or destroyedThe first law is also called the principle of conservation of energy.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Second Law of ThermodynamicsDuring every energy transfer or transformation, some energy is unusable, and is often lost as heat.The second law of thermodynamics: Every energy transfer or transformation increases the entropy (disorder) of the universeThe quality of the energy changes - becomes more disordered. (1st law states the quantity is constant)Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The two laws of thermodynamics(a) First law of thermodynamics

(b) Second law of thermodynamics

Chemicalenergy

Heat

CO2

H2O

+

Biological Order and DisorderCells create ordered structures from less ordered materials.Organisms also replace ordered forms of matter and energy with less ordered forms.Energy flows into an ecosystem in the form of light and exits in the form of heat.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The evolution of more complex organisms does not violate the second law of thermodynamics.Entropy (disorder) may decrease in an organism, but the universes total entropy increases.

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The free-energy change of a reaction GBiologists want to know which reactions occur spontaneously and which require the input of energy.For this, they need to determine energy changes that occur in chemical reactions.A living systems free energy, G, is energy that can do work when temperature and pressure are uniform, as in a living cell.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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), disorder,and temperature in Kelvin (T): G = H TSOnly processes with a negative G are spontaneous.Spontaneous processes can be harnessed to perform work.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Free Energy, Stability, and EquilibriumFree energy is a measure of a systems instability, its tendency to change to a more stable state.During a spontaneous change, free energy decreases, - G ,and the stability of a system increases.Equilibrium is a state of maximum stability.A process is spontaneous and can perform work only when it is moving toward equilibrium.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The relationship of free energy to stability, work capacity, and spontaneous change(a) Gravitational motion

(b) Diffusion

(c) Chemical reaction More free energy (higher G) Less stable Greater work capacity In 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

Less free energy (lower G) More stable Less work capacity 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

SpontaneouschangeSpontaneouschangeSpontaneouschange(b) Diffusion(c) Chemical reaction(a) Gravitational motion

Free Energy and Metabolism:Exergonic and Endergonic Reactions An exergonic reaction proceeds with a net release of free energy and is spontaneous - G

An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous +G

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Free energy changes G in exergonic and endergonic reactionsReactantsEnergyFree energyProductsAmount ofenergyreleased(G < 0)Progress of the reaction(a) Exergonic reaction: energy releasedProductsReactantsEnergyFree energyAmount ofenergyrequired(G > 0)(b) Endergonic reaction: energy requiredProgress of the reaction

Energy(a) Exergonic reaction: energy releasedProgress of the reactionFree energyProductsAmount ofenergyreleased(G < 0)Reactants

Energy(b) Endergonic reaction: energy requiredProgress of the reactionFree energyProductsAmount ofenergyrequired(G > 0)Reactants

Equilibrium and MetabolismReactions in a closed system eventually reach equilibrium and then do no work G = 0Cells are not in equilibrium; they are open systems experiencing a constant flow of materials. A defining feature of life is that metabolism is never at equilibrium.A catabolic pathway in a cell releases free energy in a series of reactions.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

ATP powers cellular work by coupling exergonic reactions to endergonic reactions = Energy CouplingA cell does three main kinds of work:ChemicalTransportMechanicalTo do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one.Most energy coupling in cells is mediated by ATP.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Structure and Hydrolysis of ATPATP (adenosine triphosphate) is the cells energy shuttleATP is composed of: ribose (a pentose sugar) adenine (a nitrogenous base) and three phosphate groupsCopyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The structure of adenosine triphosphate ATP3 Phosphate groupsRiboseAdenine

The bonds between the phosphate groups of ATPs tail can be broken by hydrolysis.Energy is released from ATP when the terminal phosphate bond is broken.This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Hydrolysis of ATP releases energy to do workInorganic phosphateEnergyAdenosine triphosphate (ATP)Adenosine diphosphate (ADP)PPPPPP++H2Oi

How ATP Performs WorkThe three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP.In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction.Overall, the coupled reactions are exergonic. Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

How ATP drives chemical work: Energy coupling using ATP hydrolysis(b) Coupled with ATP hydrolysis, an exergonic reactionAmmonia displacesthe phosphate group,forming glutamine.(a) Endergonic reaction(c) Overall free-energy changePPGluNH3NH2GluiGluADP+PATP++GluATP phosphorylatesglutamic acid,making the aminoacid less stable.GluNH3NH2Glu+GlutamicacidGlutamineAmmoniaG = +3.4 kcal/mol+21

ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant.The recipient molecule is now phosphorylated, energy rich and unstable.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

How ATP drives transport and mechanical work(b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzedMembrane proteinPiADP+PSoluteSolute transportedPiVesicleCytoskeletal trackMotor proteinProtein moved(a) Transport work: ATP phosphorylates transport proteinsATPATP

The Regeneration of ATPATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)ADP + P --> ATPThe energy to phosphorylate ADP comes from catabolic reactions in the cell.The chemical potential energy temporarily stored in ATP drives most cellular work.

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The ATP cycle PiADP+Energy fromcatabolism (exergonic,energy-releasingprocesses)Energy for cellularwork (endergonic,energy-consumingprocesses)+ H2OATP

Enzymes speed up the rate of 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 proteinEnzymes are specific. Enzymes have a shape-match with their substrates.Enzymes are named after their substrate and generally end in -ase.Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Example of an enzyme-catalyzed reaction: hydrolysis of sucrose by sucraseSucrose (C12H22O11)Glucose (C6H12O6)Fructose (C6H12O6)Sucrase

The Activation Energy EA BarrierEvery chemical reaction between molecules involves bond breaking and bond forming.The 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 heat from the surroundings.Enzymes lower the amount of EA needed, so the reaction rate is faster.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Exergonic ReactionProgress of the reactionProductsReactantsG < OTransition stateFree energyEADCBADDCCBBAA

How Enzymes Lower the EA BarrierEnzymes catalyze reactions by lowering the EA barrier.Enzymes do not affect the change in free energy (G); instead, they hasten / speed up reactions that would occur eventually.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The effect of an enzyme on activation energyProgress of the reactionProductsReactantsG is unaffectedby enzymeCourse ofreactionwithoutenzymeFree energyEAwithoutenzymeEA withenzymeis lowerCourse ofreactionwith enzyme

Substrate Specificity of EnzymesThe reactant that an enzyme acts on is called the enzymes substrate.The enzyme binds to its substrate, forming an enzyme-substrate complex (Reaction occurs)The active site is the region on the enzyme where the substrate binds (shape match).Induced fit of a substrate brings chemical groups of the active site into positions (orientation) that enhance their ability to catalyze the reaction.

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Induced fit between an enzyme and its substrateSubstrateActive siteEnzymeEnzyme-substratecomplex(b)(a)

Catalysis in the Enzymes Active SiteIn an enzymatic reaction, the substrate binds to the active site of the enzymeThe enzymes active site can lower an EA barrier byOrienting substrates correctlyStraining substrate bonds / tensionProviding a favorable microenvironmentCovalently bonding to the substrateCopyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

SubstratesEnzymeProducts arereleased.Products Substrates areconverted toproducts. Active site can lower EAand speed up a reaction. Substrates held in active site by weakinteractions, such as hydrogen bonds andionic bonds. Substrates enter active site; enzyme changes shape such that its active siteenfolds the substrates (induced fit).Activesite isavailablefor two newsubstratemolecules.Enzyme-substrateComplex:Reaction occurs532164

Effects of Local Conditions on Enzyme ActivityAn enzymes activity / reaction rate / can be affected by environmental factors such as:temperature, pH, and concentration of enzyme or substrate.Chemicals that specifically influence the enzyme.

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Effects of Temperature and pHEach enzyme has an optimal temperature in which it functions best / forming the maximum enzyme-substrate complexes --> highest rate of reaction.Each enzyme has an optimal pH in which it functions best / forming the maximum enzyme-substrate complexes --> highest rate of reaction.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Environmental factors affecting enzyme activityRate of reactionOptimal temperature forenzyme of thermophilic (heat-tolerant) bacteria Optimal temperature fortypical human enzyme(a) Optimal temperature for two enzymes(b) Optimal pH for two enzymesRate of reactionOptimal pH for pepsin(stomach enzyme) Optimal pHfor trypsin(intestinalenzyme)Temperature (C)pH5432106789100 20 40 80 60 100

Cofactors:Cofactors are nonprotein enzyme helpers.Cofactors may be inorganic (such as a metal in ionic form) or organic.Organic cofactors are called coenzymes.Coenzymes include vitamins.Inorganic cofactors include minerals and salts.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin CummingsAffect enzyme action

Enzyme InhibitorsCompetitive inhibitors bind to the active site of an enzyme, competing with the substrate.Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less able to bind with the substrate.Examples of inhibitors include toxins, poisons, pesticides, and antibiotics.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Inhibition of enzyme activity(a) Normal binding(c) Noncompetitive inhibition(b) Competitive inhibitionNoncompetitive inhibitorActive siteCompetitive inhibitorSubstrateEnzyme

Regulation of enzyme activity helps control metabolismChemical chaos would result if a cells metabolic pathways were not tightly regulated.A cell regulates metabolism by: switching on or off the genes that encode specific enzymes. or by regulating the activity of enzymes.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Allosteric Regulation of EnzymesAllosteric regulation may either inhibit or stimulate an enzymes activity.Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the proteins function at another site.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Allosteric Activation and InhibitionMost allosterically regulated enzymes are made from polypeptide subunits.Each enzyme has active and inactive forms.The binding of an activator stabilizes the active form of the enzyme.The binding of an inhibitor stabilizes the inactive form of the enzyme.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Allosteric Regulation of enzyme activityAllosteric enyzmewith four subunitsActive site(one of four)Regulatorysite (oneof four)Active formActivatorStabilized active formOscillationNon-functionalactivesiteInhibitorInactive formStabilized inactiveform(a) Allosteric activators and inhibitorsSubstrateInactive formStabilized activeform(b) Cooperativity: another type of allosteric activation

Cooperativity is a form of allosteric regulation that can amplify enzyme activity.In cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits. Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Identification of Allosteric RegulatorsAllosteric regulators are attractive drug candidates for enzyme regulation.Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Feedback Inhibition: Allosteric Enzyme RegulationIn feedback inhibition, the end product of a metabolic pathway shuts down the pathway. End product builds up and becomes and allosteric inhibitor.Allosteric inhibitor binds to an allosteric enzyme early in the pathway, shutting down the pathway.Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Feedback InhibitionIntermediate CFeedbackinhibitionIsoleucineused up bycellEnzyme 1(threoninedeaminase)End product(isoleucine)Enzyme 5Intermediate DIntermediate BIntermediate AEnzyme 4Enzyme 2Enzyme 3Initial substrate(threonine)Threoninein active siteActive siteavailableActive site ofenzyme 1 nolonger bindsthreonine;pathway isswitched off.Isoleucinebinds toallostericsite

Specific Localization of Enzymes Within the CellStructures within the cell help bring order to metabolic pathways.Some enzymes act as structural components of membranes.In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Organelles and structural order in metabolism1 mMitochondriaEnymes are embedded in the membrane and are organized in a specific sequence for an efficient metabolic pathway.

You should now be able to:Distinguish between the following pairs of terms: catabolic and anabolic pathways; kinetic and potential energy; open and closed systems; exergonic and endergonic reactions.In your own words, explain the second law of thermodynamics and explain why it is not violated by living organisms.Explain in general terms how cells obtain the energy to do cellular work.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Explain how ATP performs cellular work. Explain why an investment of activation energy is necessary to initiate a spontaneous reaction.Describe the mechanisms by which enzymes lower activation energy.Describe how allosteric regulators may inhibit or stimulate the activity of an enzyme.Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

***Figure 8.1********Figure 8.2****Figure 8.3******Figure 8.5*Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change*Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change**Figure 8.6*Figure 8.6a Free energy changes (G) in exergonic and endergonic reactions*Figure 8.6b Free energy changes (G) in exergonic and endergonic reactions***For the Cell Biology Video Space Filling Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.*Figure 8.8*For the Cell Biology Video Stick Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.

*Figure 8.9 The hydrolysis of ATP**Figure 8.10**Figure 8.11**Figure 8.12**Figure 8.13**Figure 8.14 Energy profile of an**Figure*For the Cell Biology Video Closure of Hexokinase via Induced Fit, go to Animation and Video Files.

*Figure 8.16**Figure 8.17 The active site and catalytic cycle of an enzyme***Figure 8.18***Figure 8.19****Figure 8.20****Figure 8.22 Feedback inhibition in isoleucine synthesis**Figure 8.23**