Presentation on theme: "An Introduction to Metabolism"— Presentation transcript:
1An Introduction to Metabolism Chapter 8An Introduction to Metabolism
2Overview8.1 An organism′s metabolism transforms matter and energy, subject to the laws of thermodynamics 8.2 The free–energy change of a reaction tells us whether the reaction occurs spontaneously 8.3 ATP powers cellular work by coupling exergonic reactions to endergonic reactions 8.4 Enzymes speed up metabolic reactions by lowering energy barriers 8.5 Regulation of enzyme activity helps control metabolism
3Overview: The Energy of Life The 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
5Metabolism is the totality of an organism’s chemical reactions 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
6Organization 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 enzyme
8We can picture a cell′s metabolism as an elaborate road map of the thousands of chemical reactions that occur in a cell, arranged as intersecting metabolic pathwaysAnalogous to the red, yellow, and green stoplights that control the flow of traffic, mechanisms that regulate enzymes balance metabolic supply and demand, averting deficits or surpluses of important cellular molecules
9Metabolism as a whole manages the ________________ and ___________________ resources of the cell. Some metabolic pathways release energy by breaking down complex molecules to simpler compounds
10Catabolic pathways release energy by breaking down complex molecules into simpler compounds Anabolic pathways consume energy to build complex molecules from simpler onesBioenergetics is the study of how organisms manage their energy resources
11Energy released from the downhill reactions of catabolism can be stored and then used to drive the uphill reactions of the anabolic pathways
12Forms of Energy Energy is the capacity to cause change Energy exists in various forms, some of which can perform work
13Animation: Energy Concepts Kinetic energy is energy associated with motion____________ (thermal energy) is kinetic energy associated with random movement of atoms or molecules________________ energy is energy that matter possesses because of its location or structure________________ energy is potential energy available for release in a chemical reactionEnergy can be converted from one form to anotherAnimation: Energy Concepts
14LE 8-2 On the platform, the diver has more potential energy. Diving convertspotentialenergy tokinetic energy.Climbing up convertskinetic energy ofmuscle movement topotential energy.In the water, thediver has lesspotential energy.
15Recall that catabolic pathways release energy by breaking down complex molecules. Complex molecules, such as glucose, are high in chemical energy.During a catabolic reaction, atoms are rearranged and energy is released, resulting in lower–energy breakdown products.This transformation also occurs, for example, in the engine of a car when the hydrocarbons of gasoline react explosively with oxygen, releasing the energy that pushes the pistons and producing exhaust. Although less explosive, a similar reaction of food molecules with oxygen provides chemical energy in biological systems, producing carbon dioxide and water as waste products. It is the structures and biochemical pathways of cells that enable them to release chemical energy from food molecules, powering life processes
16Organisms are energy transformers. The study of the energy transformations that occur in a collection of matter is called thermodynamics
17The Laws of Energy Transformation Two words….Scientists use the word system to denote the matter under study; they refer to the rest of the universe—everything outside the system—as the surroundings.A closed system, such as liquid in a thermos bottle, is isolated from its surroundings. In an open system, energy (and often matter) can be transferred between the system and its surroundings.Organisms are __________ systems. They absorb energy—for instance, light energy or chemical energy in the form of organic molecules—and release heat and metabolic waste products, such as carbon dioxide, to the surroundings.Two laws of thermodynamics govern energy transformations in organisms and all other collections of matter
18The First Law of Thermodynamics According to the first law of thermodynamics, the energy of the universe is constantEnergy can be transferred and transformedEnergy cannot be created or destroyedThe first law is also called the principle of conservation of energy
19The electric company does not make energy, but merely converts it to a form that is convenient to use. By converting sunlight to chemical energy, a green plant acts as an energy transformer, not an energy producer.
20LE 8-3The cheetah will convert the chemical energy of the organic molecules in its food to kinetic and other forms of energy as it carries out biological processes.What happens to this energy after it has performed work? The second law helps to answer this questionCO2ChemicalenergyHeatH2OFirst law of thermodynamicsSecond law of thermodynamics
21The Second Law of Thermodynamics If energy cannot be destroyed, why can′t organisms simply recycle their energy over and over again?During every energy transfer or transformation, some energy is unusable, often lost as ___________which is the energy associated with the random motion of atoms or molecules.
22In most energy transformations, more usable forms of energy are at least partly converted to heat, Only a small fraction of the chemical energy from the food is transformed into the motion of the cheetah; most is lost as heat, which dissipates rapidly through the surroundings
23In the process of carrying out chemical reactions that perform various kinds of work, living cells unavoidably convert organized forms of energy to heat.Can a system put heat to work?only when there is a temperature difference that results in the heat flowing from a warmer location to a cooler one.If temperature is uniform, as it is in a living cell, then the only use for heat energy generated during a chemical reaction is to warm a body of matter, such as the organism.
24Concept of EntropyThe loss of usable energy during energy transfer or transformation makes the universe more disordered.Scientists use a quantity called entropy as a measure of disorder, or randomness. The more randomly arranged a collection of matter is, the greater its entropy
25State the second law of Thermodynamics The loss of usable energy during energy transfer or transformation makes the universe more disordered…We can now state the second law of thermodynamics as follows:Every energy transfer or transformation increases the entropy of the universe.Although order can increase locally, there is an unstoppable trend toward randomization of the universe as a whole.
26In many cases, increased entropy is evident in the physical disintegration of a system′s organized structure.For example, you can observe increasing entropy in the gradual decay of an unmaintained building.Much of the increasing entropy of the universe is less apparent, however, because it appears as increasing amounts of heat and less ordered forms of matter.As the cheetah converts chemical energy to kinetic energy, it is also increasing the disorder of its surroundings by producing heat and the small molecules that are the breakdown products of food
27Biological Order and Disorder Living systems increase the entropy of their surroundings, as predicted by thermodynamic law.How do you explain….Cells create ordered structures from less organized starting materials. For example, amino acids are ordered into the specific sequences of polypeptide chains.The extremely symmetrical anatomy of a plant′s root, formed by biological processes from simpler starting materials.How do you explain evolution…The entropy of a particular system, such as an organism, may actually decrease, so long as the total entropy of the universe—the system plus its surroundings—increases. Thus, organisms are islands of low entropy in an increasingly random universe. The evolution of biological order is perfectly consistent with the laws of thermodynamics
28Biological Order and Disorder Living systems increase the entropy of their surroundings, as predicted by thermodynamic law.Question you would ask is; that cells create ordered structures from less organized starting materials. For example, amino acids are ordered into the specific sequences of polypeptide chains.
29An organism also takes in organized forms of matter and energy from the surroundings and replaces them with less ordered forms.For example, an animal obtains starch, proteins, and other complex molecules from the food it eats. As catabolic pathways break these molecules down, the animal releases carbon dioxide and water—small molecules that store less chemical energy than the food did. The depletion of chemical energy is accounted for by heat generated during metabolism.On a larger scale, energy flows into an ecosystem in the form of light and leaves in the form of heat
30why certain processes occur? The concept of entropy helps us understand why certain processes occur. It turns out that for a process to occur on its own (spontaneously), without outside help (an input of energy), it must ____________________ the entropy of the universe.
31Spontaneous process…Let′s first agree to use the word spontaneous for a process that can occur without an input of energy.The word spontaneous does not imply that such a process would occur quickly. Some spontaneous processes may be virtually instantaneous, such as an explosion, while others may be much slower, such as the rusting of an old car over time.
32Nonspontaneous process… A process that cannot occur on its own is said to be nonspontaneous; it will happen only if energy is added to the system.We know from experience that certain events occur spontaneously and others do not. For instance, we know that water flows downhill spontaneously, but moves uphill only with an input of energy, for instance when a machine pumps the water against gravity.In fact, another way to state the second law is: For a process to occur spontaneously, it must increase the entropy of the universe.
33Living cells unavoidably convert organized forms of energy to heat Spontaneous 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
34Q1a) How does the second LAW OF THERMODYNAMICS explain the diffusion of a substance across a membrane?
35Q2a) Describe the forms of energy found in an apple as it grows on a tree, then falls and is digested by someone who eats it.
36Q3a) How does the disease ‘Familial Hypercholesterolemia” cause high levels of cholesterol in the blood?
37Q1. If a Paramecium were to swim from a HYPOTONIC environment to an ISOTONIC one, how would the activity of contractile vacuole be affected? Explain with the help of a diagrammatic representation.
38Q2. Explain why the sodium potassium pump would not be considered a COTRANSPORTER.
39LE 7-16 Cytoplasmic Na+ bonds to the sodium-potassium pump EXTRACELLULARFLUID[Na+] high[K+] lowNa+Na+Na+Na+Na+Na+Na+Na+[Na+] low[K+] highATPPNa+PCYTOPLASMADPCytoplasmic Na+ bonds tothe sodium-potassium pumpNa+ binding stimulatesphosphorylation by ATP.Phosphorylation causesthe protein to change itsconformation, expelling Na+to the outside.K+K+K+K+K+PPK+Extracellular K+ bindsto the protein, triggeringrelease of the phosphategroup.Loss of the phosphaterestores the protein’soriginal conformation.K+ is released and Na+sites are receptive again;the cycle repeats.
41Proton pump Diffusion of H+ Sucrose-H+ cotransporter Sucrose LE 7-19–+ATPH+H+–+Proton pumpH+H+–+H+–+H+Diffusionof H+Sucrose-H+cotransporterH+–+–+Sucrose
42Q3. As a cell grows, its plasma membrane expands Q3. As a cell grows, its plasma membrane expands. Which type of bulk transport process is involved. Explain.
43cytoplasm nucleus cell membrane nuclear pore protein secreted rough ER transportvesicleGolgiapparatussmooth ERrough ERnuclear porenucleusribosomecellmembraneprotein secretedcytoplasm
44Concept 8.2: The free-energy change of a reaction tells us whether the reaction occurs spontaneously Biologists 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
45Free–Energy Change, ΔGIn 1878, J. Willard Gibbs, a professor at Yale, defined a very useful function called the Gibbs free energy of a system (without considering its surroundings), symbolized by the letter G .Free energy measures the portion of a system′s energy that can perform work when temperature and pressure are uniform throughout the system, as in a living cell.Let′s consider how we determine the free energy change that occurs when a system changes—for example, during a chemical reaction
46The change in free energy (∆G) during a process is related to the change in enthalpy, or change in total energy (∆H), and change in entropy (T∆S):∆G = ∆H - T∆SOnly processes with a negative ∆G are spontaneousSpontaneous processes can be harnessed to perform work
48Free Energy, Stability, and Equilibrium when a process occurs spontaneously in a system, we can be sure that ΔG is negative.Another way to think of ΔG is to realize that it represents the difference between the free energy of the final state and the free energy of the initial state
50Free Energy, Stability, and Equilibrium A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cellFree energy is a measure of a system’s instability, its…tendency to change to a more stable stateDuring a spontaneous change, free energy _______________ and the stability of a system increases
52Thus, ΔG can only be negative when the process involves a __________of free energy during the change from initial state to final state.Because it has less free energy, the system in its final state is less likely to change and is therefore more stable than it was previously
53The relationship of free energy to stability, work capacity, and spontaneous change. _____________ systems are rich in free energy, or G. They have a tendency to change __________________ to a more stable state (bottom), and it is possible to harness this “downhill” change to perform _____________
54Equilibrium is a state of ______________ stability A process is spontaneous and can perform work only when it is moving toward equilibrium
55Another term for a state of maximum stability is equilibrium There is an important relationship between free energy and equilibrium, including chemical equilibrium.reversible ……there is no further net change in the relative concentration of products and reactants. As a reaction proceeds toward equilibrium, the free energy of the mixture of reactants and products ________________.Free energy increases when a reaction is somehow pushed away from equilibrium, perhaps by removing some of the products (and thus changing their concentration relative to that of the reactants).For a system at equilibrium, G is at its lowest possible value in that system.
56Equilibrium state as an energy valley… G lowest value…can it change spontaneously?Because a system at equilibrium cannot spontaneously change, it can do no work.A process is spontaneous and can perform work only when it is moving toward equilibrium
57Free Energy and Metabolism The concept of free energy can be applied to the chemistry of life’s processes
58Exergonic and Endergonic Reactions in Metabolism An exergonic reaction proceeds with a net release of free energy and is spontaneousAn endergonic reaction absorbs free energy from its surroundings and is nonspontaneous
59Progress of the reaction LE 8-6aReactantsAmount ofenergyreleased(G < 0)Free energyEnergyProductsProgress of the reactionExergonic reaction: energy released
60Progress of the reaction LE 8-6bProductsAmount ofenergyrequired(G > 0)Free energyEnergyReactantsProgress of the reactionEndergonic reaction: energy required
61Equilibrium and Metabolism Reactions in a closed system eventually reach equilibrium and then do no workIs cell’s metabolism at equilibrium?Cells are not in equilibrium;they are open systems experiencing a constant flow of materialsA catabolic pathway in a cell releases free energy in a series of reactionsClosed and open hydroelectric systems can serve as analogies
62LE 8-7aG < 0G = 0A closed hydroelectric system
63LE 8-7bG < 0A catabolic pathway in a cell releases free energy in a series of reactionsAn open hydroelectric system
64G < 0 G < 0 G < 0 A multistep open hydroelectric system
65Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions A cell does three main kinds of work:MechanicalTransportChemicalTo do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one
66The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) is the cell’s energy shuttleATP provides energy for cellular functions
68Energy is released from ATP when the terminal phosphate bond is broken The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysisEnergy is released from ATP when the terminal phosphate bond is brokenPPPAdenosine triphosphate (ATP)H2OP+PP+EnergyiInorganic phosphateAdenosine diphosphate (ADP)
69This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselvesPPPAdenosine triphosphate (ATP)H2OP+PP+EnergyiInorganic phosphateAdenosine diphosphate (ADP)
70In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reactionOverall, the coupled reactions are exergonic
71Glutamic acid Ammonia Glutamine ATP H2O ADP LE 8-10Endergonic reaction: DG is positive, reactionis not spontaneousNH2+NH3DG = +3.4 kcal/molGluGluGlutamicacidAmmoniaGlutamineExergonic reaction: DG is negative, reactionis spontaneousATP+H2OADPP+DG = –7.3 kcal/moliCoupled reactions: Overall DG is negative;together, reactions are spontaneousDG = –3.9 kcal/mol
72How ATP Performs Work?ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactantThe recipient molecule is now phosphorylatedThe three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP
73Reactants: Glutamic acid LE 8-11PiPMotor proteinProtein movedMechanical work: ATP phosphorylates motor proteinsMembraneproteinADPATP+PiPPiSoluteSolute transportedTransport work: ATP phosphorylates transport proteinsPNH2+NH3Glu+PiGluReactants: Glutamic acidand ammoniaProduct (glutamine)madeChemical work: ATP phosphorylates key reactants
74The Regeneration of ATP ATP is a renewable resource that is regenerated by addition of a phosphate group to ADPThe energy to phosphorylate ADP comes from catabolic reactions in the cellThe chemical potential energy temporarily stored in ATP drives most cellular work
75LE 8-12Because both directions of a reversible process cannot go downhill, the regeneration of ATP from ADP and Pi is necessarily endergonicATPEnergy for cellular work(endergonic, energy-consuming processes)Energy from catabolism(energonic, energy-yielding processes)ADPP+i
76Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers A catalyst is a chemical agent that speeds up a reaction without being consumed by the reactionAn enzyme is a catalytic protein
77LE 8-13Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reactionSucroseC12H22O11GlucoseC6H12O6FructoseC6H12O6
78The Activation Energy Barrier Every chemical reaction between molecules involves both bond breaking and bond forming.Changing one molecule into another generally involves contorting the starting molecule into a highly unstable state before the reaction can proceed.This contortion can be compared to a metal key ring when you bend it and pry it open to add a new key. The key ring is highly unstable in its opened form but returns to a stable state once the key is threaded all the way onto the ring.
79To reach the contorted state where bonds can change, reactant molecules must absorb energy from their surroundings.When the new bonds of the product molecules form, energy is released as heat, and the molecules return to stable shapes with lower energy.The initial investment of energy for starting a reaction—the energy required to contort the reactant molecules so the bonds can change—is known as the free energy of activation, or activation energy, abbreviated EA.
80We can think of activation energy as the amount of energy needed to push the reactants over an energy barrier, or hill, so that the “downhill” part of the reaction can begin.Figure 8.14 graphs the energy changes for a hypothetical reaction that swaps portions of two reactant molecules:Every 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 heat from the surroundings
81Energy profile of an exergonic reaction Energy profile of an exergonic reaction. Thermodynamically, this is an exergonic reaction, with a negative ΔG, and the reaction occurs spontaneously.However, the activation energy (EA) provides a barrier that determines the rate of the reaction
82The energizing, or activation, of the reactants is represented by the uphill portion of the graph, with the free–energy content of the reactant molecules increasing.
83At the summit, the reactants are in an unstable condition known as the transition state: They are activated, and the breaking and making of bonds can occur.
84The bond–forming phase of the reaction corresponds to the downhill part of the curve, which shows the loss of free energy by the molecules
85Activation energy is often supplied in the form of heat that the reactant molecules absorb from the surroundings.The bonds of the reactants break only when the molecules have absorbed enough energy to become unstable and are therefore more reactiveThe absorption of thermal energy increases the speed of the reactant molecules, so they collide more often and more forcefully.
86Also, thermal agitation of the atoms in the molecules makes the bonds more likely to break. As the molecules settle into their new, more stable bonding arrangements, energy is released to the surroundings.If the reaction is exergonic, EA will be repaid with dividends, as the formation of new bonds releases more energy than was invested in the breaking of old bonds.
87The reactants must absorb enough energy to reach the top of the activation energy barrier before the reaction can occur.For some reactions, EA is modest enough that even at room temperature there is sufficient thermal energy for many of the reactants to reach the transition state in a short time.In most cases, however, EA is so high and the transition state is reached so rarely that the reaction will hardly proceed at all.In these cases, the reaction will occur at a noticeable rate only if the reactants are heated.
88The spark plugs in an automobile engine energize the gasoline–oxygen mixture so that the molecules reach the transition state and react; only then can there be the explosive release of energy that pushes the pistons. Without a spark, a mixture of gasoline hydrocarbons and oxygen will not react because the EA barrier is too high.
89Proteins, DNA, and other complex molecules of the cell are rich in free energy and have the potential to decompose spontaneously; that is, the laws of thermodynamics favor their breakdown.Why these molecules persist in cells?At the temperature of a cell, only few molecules can make it over the hump of activation energy.However, the barriers for selected reactions must occasionally be surmounted for cells to carry out the processes necessary for life.
90One solution is…Heat speeds a reaction by allowing reactants to attain the transition state more often,but this solution would be inappropriate for biological systems.First, high temperature denatures proteins and kills cells.Second, heat would speed up all reactions, not just those that are necessary.Organisms therefore use an alternative: catalysis.
91Animation: How Enzymes Work Enzymes catalyze reactions by lowering the EA barrierEnzymes do not affect the change in free-energy (∆G); instead, they hasten reactions that would occur eventuallyAnimation: How Enzymes Work
92An enzyme catalyzes a reaction by lowering the EA barrier, enabling the reactant molecules to absorb enough energy to reach the transition state even at moderate temperatures.
93An enzyme cannot change the ΔG for a reaction It cannot make an endergonic reaction exergonic.Enzymes can only hasten reactions that would occur eventually anyway,But this function makes it possible for the cell to have a dynamic metabolism, routing chemical traffic smoothly through the cell.And because enzymes are very selective in the reactions they catalyze, they determine which chemical processes will be going on in the cell at any particular time.
94Progress of the reaction LE 8-15Course ofreactionwithoutenzymeEAwithoutenzymeEA withenzymeis lowerReactantsFree energyCourse ofreactionwith enzymeDG is unaffectedby enzymeProductsProgress of the reaction
95Substrate Specificity of Enzymes The reactant that an enzyme acts on is called the enzyme’s substrate
96Substrate Specificity of Enzymes The reactant that an enzyme acts on is called the enzyme’s substrateThe enzyme binds to its substrate, forming an enzyme-substrate complex
97Substrate Specificity of Enzymes The 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
98Substrate Specificity of Enzymes Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction
99The reaction catalyzed by each enzyme is very specific; an enzyme can recognize its specific substrate even among closely related compounds, such as isomers.What accounts for this molecular recognition?Recall that enzymes are proteins, and proteins are macromolecules with unique three–dimensional conformations.The specificity of an enzyme results from its shape, which is a consequence of its amino acid sequence
101LE 8-17 Substrates enter active site; enzyme changes shape so its active siteembraces the substrates (induced fit).Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.Active site (and R groups ofits amino acids) can lower EAand speed up a reaction byacting as a template forsubstrate orientation,stressing the substratesand stabilizing thetransition state,providing a favorablemicroenvironment,participating directly in thecatalytic reaction.SubstratesEnzyme-substratecomplexActivesite isavailablefor two newsubstratemolecules.EnzymeProducts arereleased.Substrates areconverted intoproducts.Products
102Catalysis in the Enzyme’s Active Site In an enzymatic reaction, the substrate binds to the active siteMechanism?The active site can lower an EA barrier by- Orienting substrates correctlyStraining substrate bondsProviding a favorable microenvironmentCovalently bonding to the substrate
103The enzyme always catalyzes the reaction in the direction of equilibrium.
104The rate at which a particular amount of enzyme converts substrate to product is partly a function of the initial concentration of the substrate:The more substrate molecules are available, the more frequently they access the active sites of the enzyme molecules.However, there is a limit to how fast the reaction can be pushed by adding more substrate to a fixed concentration of enzyme.
105At some point, the concentration of substrate will be high enough that all enzyme molecules have their active sites engaged.At this substrate concentration, the enzyme is said to be saturated, and the rate of the reaction is determined by the speed at which the active site can convert substrate to product.When an enzyme population is saturated, the only way to increase the rate of product formation is to add more enzyme.As soon as the product exits an active site, another substrate molecule enters.
106Effects of Local Conditions on Enzyme Activity An enzyme’s activity can be affected by:General environmental factors, such as temperature and pHChemicals that specifically influence the enzyme
107Effects of Temperature and pH Each enzyme has an optimal temperature in which it can functionEach enzyme has an optimal pH in which it can function
108LE 8-18 Optimal temperature for typical human enzyme enzyme of thermophilic(heat-tolerantbacteria)Rate of reaction20406080100Temperature (°C)Optimal temperature for two enzymesOptimal pH for pepsin(stomach enzyme)Optimal pHfor trypsin(intestinalenzyme)Rate of reaction12345678910pHOptimal pH for two enzymes
109Cofactors Cofactors are nonprotein enzyme helpers Coenzymes are organic cofactors
110Enzyme 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 effective
111LE 8-19 A substrate can Substrate bind normally to the active site of anenzyme.SubstrateActive siteEnzymeNormal bindingA competitiveinhibitor mimics thesubstrate, competingfor the active site.CompetitiveinhibitorCompetitive inhibitionA noncompetitiveinhibitor binds to theenzyme away from theactive site, altering theconformation of theenzyme so that itsactive site no longerfunctions.Noncompetitive inhibitorNoncompetitive inhibition
112Toxins and poisons are often irreversible enzyme inhibitors. An example is sarin, a nerve gas that caused the death of several people and injury to many others when it was released by terrorists in the Tokyo subway in 1995.This small molecule binds covalently to the R group on the amino acid serine, which is found in the active site of acetylcholinesterase, an enzyme important in the nervous system.
113Other examples include the pesticides DDT and parathion, inhibitors of key enzymes in the nervous system.Finally, many antibiotics are inhibitors of specific enzymes in bacteria.For instance, penicillin blocks the active site of an enzyme that many bacteria use to make their cell walls.
114Citing enzyme inhibitors that are metabolic poisons may give the impression that enzyme inhibition is generally abnormal and harmful.In fact, molecules naturally present in the cell often regulate enzyme activity by acting as inhibitors.Such regulation—selective inhibition—is essential to the control of cellular metabolism
115Concept 8.5: Regulation of enzyme activity helps control metabolism Chemical chaos would result if a cell’s metabolic pathways were not tightly regulatedTo regulate metabolic pathways, the cell switches on or off the genes that encode specific enzymesOr, by regulating the activity of enzymes once they are madeProduction Level (gene level)Activity Level…
116Allosteric Regulation of Enzymes Allosteric regulation is the term used to describe cases where a protein’s function at one site is affected by binding of a regulatory molecule at another siteAllosteric regulation may either inhibit or stimulate an enzyme’s activity
117Allosteric Activation and Inhibition Most 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
118LE 8-20aAllosteric activatorstabilizes active form.Allosteric enzymewith four subunitsActive site(one of four)Allosteric regulation is the term used to describe cases where a protein’s function at one site is affected by binding of a regulatory molecule at another siteRegulatorysite (oneof four)ActivatorActive formStabilized active formOscillationAllosteric inhibitorstabilizes inactive form.Non-functionalactive siteInhibitorInactive formStabilized inactiveformAllosteric activators and inhibitors
119Fluctuating concentrations of regulators can cause a sophisticated pattern of response in the activity of cellular enzymes.The products of ATP hydrolysis (ADP and Pi), for example, play a major role in balancing the flow of traffic between anabolic and catabolic pathwaysHow?By their effects on key enzymes.
120For example, ATP binds to several catabolic enzymes allosterically, lowering their affinity for substrate and thus inhibiting their activity.ADP, however, functions as an activator of the same enzymes.This is logical because a major function of catabolism is to regenerate ATP.Glucose E ATPADP
121If ATP production lags behind its use, ADP accumulates and activates these key enzymes that speed up catabolism, producing more ATP.If the supply of ATP exceeds demand, then catabolism slows down as ATP molecules accumulate and bind these same enzymes, inhibiting them.ATP, ADP, and other related molecules also affect key enzymes in anabolic pathways
122Cooperativity 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
123Binding of one substrate molecule to LE 8-20bBinding of one substrate molecule toactive site of one subunit locks allsubunits in active conformation.SubstrateInactive formStabilized active formCooperativity another type of allosteric activation
124Feedback 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
125LE 8-21 Initial substrate (threonine) Active site available Threonine in active siteEnzyme 1(threoninedeaminase)Isoleucineused up bycellIntermediate AFeedbackinhibitionEnzyme 2Active site ofenzyme 1 can’tbindtheoninepathway offIntermediate BEnzyme 3Intermediate CIsoleucinebinds toallostericsiteEnzyme 4Intermediate DEnzyme 5End product(isoleucine)
126Specific Localization of Enzymes Within the Cell Structures within the cell help bring order to metabolic pathwaysSome enzymes act as structural components of membranesSome enzymes reside in specific organelles, such as enzymes for cellular respiration being located in mitochondria
127LE 8-22Mitochondria,sites of cellular respiration1 µm