Ch 8: Introduction to Metabolism
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Transcript of Ch 8: Introduction to Metabolism
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LECTURE PRESENTATIONSFor CAMPBELL BIOLOGY, NINTH EDITION
Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson
© 2011 Pearson Education, Inc.
Lectures byErin Barley
Kathleen Fitzpatrick
An Introduction to Metabolism
Chapter 8
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Overview: The Energy of Life
• The 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
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Figure 8.1
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Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics
• Metabolism is the totality of an organism’s chemical reactions
• Metabolism is an emergent property of life that arises from interactions between molecules within the cell
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Organization of the Chemistry of Life into Metabolic Pathways
• A metabolic pathway begins with a specific molecule and ends with a product
• Each step is catalyzed by a specific enzyme
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Figure 8.UN01
Enzyme 1 Enzyme 2 Enzyme 3
Reaction 1 Reaction 2 Reaction 3ProductStarting
molecule
A B C D
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• Catabolic pathways 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
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• Anabolic pathways consume 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 Energy
• Energy is the capacity to cause change• Energy exists in various forms, some of which
can perform work
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• 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
• Energy can be converted from one form to another
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Animation: Energy Concepts
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Figure 8.2 A diver has more potentialenergy on the platformthan in the water.
Diving convertspotential energy tokinetic energy.
Climbing up converts the kineticenergy of muscle movementto potential energy.
A diver has less potentialenergy in the waterthan on the platform.
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The Laws of Energy Transformation
• Thermodynamics is the study of energy transformations
• A isolated 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
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The First Law of Thermodynamics
• According to the first law of thermodynamics, the energy of the universe is constant
– Energy can be transferred and transformed, but it cannot be created or destroyed
• The first law is also called the principle of conservation of energy
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The Second Law of Thermodynamics
• During every energy transfer or transformation, some energy is unusable, and is often lost as heat
• According to the second law of thermodynamics
– Every energy transfer or transformation increases the entropy (disorder) of the universe
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Figure 8.3
(a) First law of thermodynamics (b) Second law of thermodynamics
Chemicalenergy
Heat
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Figure 8.3a
(a) First law of thermodynamics
Chemicalenergy
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Figure 8.3b
(b) Second law of thermodynamics
Heat
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• Living cells unavoidably convert organized forms of energy to heat
• Spontaneous processes occur without energy input; they can happen quickly or slowly
• For a process to occur without energy input, it must increase the entropy of the universe
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Biological Order and Disorder
• Cells 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
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Figure 8.4
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Figure 8.4a
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Figure 8.4b
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• The evolution of more complex organisms does not violate the second law of thermodynamics
• Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases
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Concept 8.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously
• Biologists want to know which reactions occur spontaneously and which require input of energy
• To do so, they need to determine energy changes that occur in chemical reactions
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Free-Energy Change, ∆G
• A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell
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• 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), and temperature in Kelvin (T)
∆G = ∆H – T∆S• Only processes with a negative ∆G are
spontaneous• Spontaneous processes can be harnessed to
perform work
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Free Energy, Stability, and Equilibrium
• Free energy is a measure of a system’s instability, its tendency to change to a more stable state
• During a spontaneous change, free energy decreases 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
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Figure 8.5
• 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
(a) Gravitational motion (b) Diffusion (c) Chemical reaction
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Figure 8.5a
• 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
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Figure 8.5b
(a) Gravitational motion (b) Diffusion (c) Chemical reaction
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Free Energy and Metabolism
• The concept of free energy can be applied to the chemistry of life’s processes
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Exergonic and Endergonic Reactions in Metabolism
• An exergonic reaction proceeds with a net release of free energy and is spontaneous
• An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous
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Figure 8.6 (a) Exergonic reaction: energy released, spontaneous
(b) Endergonic reaction: energy required, nonspontaneous
Reactants
EnergyProducts
Progress of the reaction
Amount of energy
released(∆G < 0)
ReactantsEnergy
Products
Amount of energy
required(∆G > 0)
Progress of the reaction
Fre
e e
ne
rgy
Fre
e e
ne
rgy
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Figure 8.6a
(a) Exergonic reaction: energy released, spontaneous
Reactants
EnergyProducts
Progress of the reaction
Amount of energy
released(∆G < 0)
Fre
e e
ner
gy
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Figure 8.6b
(b) Endergonic reaction: energy required, nonspontaneous
ReactantsEnergy
Products
Amount of energy
required(∆G > 0)
Progress of the reaction
Fre
e e
ne
rgy
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Equilibrium and Metabolism
• Reactions in a closed system eventually reach equilibrium and then do no work
• Cells 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
• Closed and open hydroelectric systems can serve as analogies
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Figure 8.7
(a) An isolated hydroelectric system
(b) An open hydro- electric system
(c) A multistep open hydroelectric system
∆G < 0
∆G < 0
∆G < 0∆G < 0
∆G < 0
∆G = 0
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Figure 8.7a
(a) An isolated hydroelectric system
∆G < 0 ∆G = 0
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Figure 8.7b
(b) An open hydroelectric system
∆G < 0
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Figure 8.7c
(c) A multistep open hydroelectric system
∆G < 0
∆G < 0
∆G < 0
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Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions
• A cell does three main kinds of work– Chemical– Transport– Mechanical
• To 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
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The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate) is the cell’s energy shuttle
• ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups
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Figure 8.8
(a) The structure of ATP
Phosphate groups
Adenine
Ribose
Adenosine triphosphate (ATP)
Energy
Inorganicphosphate
Adenosine diphosphate (ADP)
(b) The hydrolysis of ATP
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Figure 8.8a
(a) The structure of ATP
Phosphate groups
Adenine
Ribose
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Figure 8.8b
Adenosine triphosphate (ATP)
Energy
Inorganicphosphate
Adenosine diphosphate (ADP)
(b) The hydrolysis of ATP
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• The bonds between the phosphate groups of ATP’s 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
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How the Hydrolysis of ATP Performs Work
• The 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
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Figure 8.9
Glutamicacid
Ammonia Glutamine
(b)Conversionreactioncoupledwith ATPhydrolysis
Glutamic acidconversionto glutamine
(a)
(c) Free-energychange forcoupledreaction
Glutamicacid
GlutaminePhosphorylatedintermediate
GluNH3 NH2
Glu∆GGlu = +3.4 kcal/mol
ATP ADP ADP
NH3
Glu Glu
PP i
P iADP
GluNH2
∆GGlu = +3.4 kcal/mol
Glu GluNH3 NH2
ATP
∆GATP = −7.3 kcal/mol∆GGlu = +3.4 kcal/mol
+ ∆GATP = −7.3 kcal/mol
Net ∆G = −3.9 kcal/mol
1 2
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• ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant
• The recipient molecule is now called a phosphorylated intermediate
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Figure 8.10Transport protein Solute
ATP
P P i
P iADP
P iADPATPATP
Solute transported
Vesicle Cytoskeletal track
Motor protein Protein andvesicle moved
(b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed.
(a) Transport work: ATP phosphorylates transport proteins.
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The Regeneration of ATP
• ATP 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 cell
• The ATP cycle is a revolving door through which energy passes during its transfer from catabolic to anabolic pathways
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Figure 8.11
Energy fromcatabolism (exergonic,energy-releasingprocesses)
Energy for cellularwork (endergonic,energy-consumingprocesses)
ATP
ADP P i
H2O
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Concept 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 reaction
• An enzyme is a catalytic protein• Hydrolysis of sucrose by the enzyme sucrase
is an example of an enzyme-catalyzed reaction
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Figure 8.UN02
Sucrase
Sucrose(C12H22O11)
Glucose(C6H12O6)
Fructose(C6H12O6)
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The Activation Energy Barrier
• Every 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 thermal energy that the reactant molecules absorb from their surroundings
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Figure 8.12
Transition state
Reactants
Products
Progress of the reaction
Fre
e e
ne
rgy EA
∆G < O
A B
C D
A B
C D
A B
C D
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How Enzymes Lower the EA Barrier
• Enzymes catalyze reactions by lowering the EA barrier
• Enzymes do not affect the change in free energy (∆G); instead, they hasten reactions that would occur eventually
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Animation: How Enzymes Work
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Figure 8.13
Course ofreactionwithoutenzyme
EA
withoutenzyme
EA withenzymeis lower
Course ofreactionwith enzyme
Reactants
Products
∆G is unaffectedby enzyme
Progress of the reaction
Fre
e e
ner
gy
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Substrate Specificity of Enzymes
• The reactant that an enzyme acts on is called the enzyme’s substrate
• The enzyme binds to its substrate, forming an enzyme-substrate complex
• The active site is the region on the enzyme where the substrate binds
• Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction
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Figure 8.14
Substrate
Active site
Enzyme Enzyme-substratecomplex
(a) (b)
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Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction, the substrate binds to the active site of the enzyme
• The active site can lower an EA barrier by
– Orienting substrates correctly– Straining substrate bonds– Providing a favorable microenvironment– Covalently bonding to the substrate
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Figure 8.15-1
Substrates
Substrates enter active site.
Enzyme-substratecomplex
Substrates are heldin active site by weakinteractions.
12
Enzyme
Activesite
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Figure 8.15-2
Substrates
Substrates enter active site.
Enzyme-substratecomplex
Substrates are heldin active site by weakinteractions.
Active site canlower EA and speedup a reaction.
12
3
Substrates areconverted toproducts.
4
Enzyme
Activesite
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Figure 8.15-3
Substrates
Substrates enter active site.
Enzyme-substratecomplex
Enzyme
Products
Substrates are heldin active site by weakinteractions.
Active site canlower EA and speedup a reaction.
Activesite is
availablefor two new
substratemolecules.
Products arereleased.
Substrates areconverted toproducts.
12
3
45
6
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Effects of Local Conditions on Enzyme Activity
• An enzyme’s activity can be affected by– General environmental factors, such as
temperature and pH– Chemicals that specifically influence the
enzyme
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Effects of Temperature and pH
• Each enzyme has an optimal temperature in which it can function
• Each enzyme has an optimal pH in which it can function
• Optimal conditions favor the most active shape for the enzyme molecule
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Figure 8.16
Optimal temperature fortypical human enzyme (37°C)
Optimal temperature forenzyme of thermophilic
(heat-tolerant)bacteria (77°C)
Temperature (°C)(a) Optimal temperature for two enzymes
Ra
te o
f re
ac
tio
nR
ate
of
rea
cti
on
120100806040200
0 1 2 3 4 5 6 7 8 9 10pH
(b) Optimal pH for two enzymes
Optimal pH for pepsin(stomachenzyme)
Optimal pH for trypsin(intestinal
enzyme)
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Figure 8.16a
Optimal temperature fortypical human enzyme (37°C)
Optimal temperature forenzyme of thermophilic
(heat-tolerant)bacteria (77°C)
Temperature (°C)(a) Optimal temperature for two enzymes
Ra
te o
f re
acti
on
120100806040200
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Figure 8.16b
Rat
e o
f re
act
ion
0 1 2 3 4 5 6 7 8 9 10pH
(b) Optimal pH for two enzymes
Optimal pH for pepsin(stomachenzyme)
Optimal pH for trypsin(intestinal
enzyme)
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Cofactors
• Cofactors are nonprotein enzyme helpers• Cofactors may be inorganic (such as a metal in
ionic form) or organic• An organic cofactor is called a coenzyme• Coenzymes include vitamins
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Enzyme Inhibitors
• Competitive 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 effective
• Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
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Figure 8.17
(a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition
Substrate
Activesite
Enzyme
Competitiveinhibitor
Noncompetitiveinhibitor
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The Evolution of Enzymes
• Enzymes are proteins encoded by genes• Changes (mutations) in genes lead to changes
in amino acid composition of an enzyme• Altered amino acids in enzymes may alter their
substrate specificity• Under new environmental conditions a novel
form of an enzyme might be favored
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Figure 8.18
Two changed amino acids werefound near the active site.
Active site
Two changed amino acidswere found in the active site.
Two changed amino acidswere found on the surface.
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Concept 8.5: Regulation of enzyme activity helps control metabolism
• Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated
• A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes
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Allosteric Regulation of Enzymes
• Allosteric regulation may either inhibit or stimulate an enzyme’s activity
• Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site
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Allosteric Activation and Inhibition
• Most 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
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Figure 8.19
Regulatorysite (oneof four)
(a) Allosteric activators and inhibitors
Allosteric enzymewith four subunits
Active site(one of four)
Active form
Activator
Stabilized active form
Oscillation
Non-functionalactive site
Inactive formInhibitor
Stabilized inactiveform
Inactive form
Substrate
Stabilized activeform
(b) Cooperativity: another type of allosteric activation
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Figure 8.19a
Regulatory site (one of four)
(a) Allosteric activators and inhibitors
Allosteric enzymewith four subunits
Active site(one of four)
Active form
Activator
Stabilized active form
Oscillation
Nonfunctionalactive site
Inactive formInhibitor
Stabilized inactive form
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Figure 8.19b
Inactive form
Substrate
Stabilized activeform
(b) Cooperativity: another type of allosteric activation
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• Cooperativity is a form of allosteric regulation that can amplify enzyme activity
• One substrate molecule primes an enzyme to act on additional substrate molecules more readily
• Cooperativity is allosteric because binding by a substrate to one active site affects catalysis in a different active site
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Identification of Allosteric Regulators
• Allosteric regulators are attractive drug candidates for enzyme regulation because of their specificity
• Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses
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Figure 8.20
Caspase 1 Activesite
Substrate
SH SH
SH
Known active form Active form canbind substrate
Allostericbinding site
Allostericinhibitor
Hypothesis: allostericinhibitor locks enzymein inactive form
Caspase 1
Active form Allostericallyinhibited form
Inhibitor
Inactive form
EXPERIMENT
RESULTS
Known inactive form
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Figure 8.20a
Caspase 1 Activesite
Substrate
SH SH
SH
Known active form Active form canbind substrate
Allostericbinding site
Allostericinhibitor
Hypothesis: allostericinhibitor locks enzymein inactive form
EXPERIMENT
Known inactive form
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Figure 8.20b
Caspase 1
Active form Allostericallyinhibited form
Inhibitor
Inactive form
RESULTS
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Feedback Inhibition
• In feedback inhibition, the end product of a metabolic pathway shuts down the pathway
• Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed
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Figure 8.21
Active siteavailable
Isoleucineused up bycell
Feedbackinhibition
Active site ofenzyme 1 isno longer ableto catalyze theconversionof threonine tointermediate A;pathway isswitched off. Isoleucine
binds toallostericsite.
Initial substrate(threonine)
Threoninein active site
Enzyme 1(threoninedeaminase)
Intermediate A
Intermediate B
Intermediate C
Intermediate D
Enzyme 2
Enzyme 3
Enzyme 4
Enzyme 5
End product(isoleucine)
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Specific Localization of Enzymes Within the Cell
• Structures 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
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Figure 8.22
Mitochondria
The matrix containsenzymes in solution thatare involved in one stage
of cellular respiration.
Enzymes for anotherstage of cellular
respiration areembedded in theinner membrane.
1 µm
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Figure 8.22a
1 µm
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Figure 8.UN03
Course ofreaction withoutenzyme
EA withoutenzyme EA with
enzymeis lower
Course ofreactionwith enzyme
Reactants
Products
∆G is unaffectedby enzyme
Progress of the reaction
Fre
e e
ner
gy
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Figure 8.UN04
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Figure 8.UN05
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Figure 8.UN06
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Figure 8.UN07