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An Introduction An Introduction to Metabolismto Metabolism

chapter 8chapter 8

Energy & MatterEnergy & Matter

Universe is composed of 2 things ……Universe is composed of 2 things ……

EnergyEnergy Ability to do workAbility to do work

o Force on an object that causes it to moveForce on an object that causes it to move

MatterMatter Anything that has mass and occupies Anything that has mass and occupies

spacespace Atoms/elementsAtoms/elements

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MetabolismMetabolismtransforming matter and transforming matter and

energyenergy

Metabolism -- totality of an organism’s Metabolism -- totality of an organism’s chemical reactionschemical reactions Arises from interactions between molecules Arises from interactions between molecules

within the cellwithin the cell

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Organization of the Organization of the Chemistry of Life into Chemistry of Life into Metabolic PathwaysMetabolic Pathways

A metabolic pathway begins with a A metabolic pathway begins with a specific molecule and ends with a specific molecule and ends with a productproduct

Each step is catalyzed by a specific Each step is catalyzed by a specific enzymeenzyme

Enzyme 1

A BReaction 1

Enzyme 2

CReaction 2

Enzyme 3

DReaction 3

ProductStartingmolecule

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Catabolic pathways -- release energy Catabolic pathways -- release energy break down complex molecules into simpler break down complex molecules into simpler

compoundscompounds

Anabolic pathways -- consume energy Anabolic pathways -- consume energy build complex molecules from simpler onesbuild complex molecules from simpler ones

Bioenergetics -- study of how organisms Bioenergetics -- study of how organisms manage their energy resourcesmanage their energy resources

Kinds of PathwaysKinds of Pathways

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Chemical ReactionsChemical Reactions

FunctionalityFunctionality CatabolicCatabolic AnabolicAnabolic

Energy RequirementsEnergy Requirements EndergonicEndergonic ExergonicExergonic

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Chemical ReactionsChemical Reactions

Reactions can be categorized as Reactions can be categorized as exergonicexergonic or or endergonicendergonic based based on energy gain or losson energy gain or loss

Chemical reactions require initial Chemical reactions require initial energy input (energy input (activation energyactivation energy))

Molecules need to be moving with Molecules need to be moving with sufficient collision speedsufficient collision speed

The electrons of an atom repel other The electrons of an atom repel other atoms and inhibit bond formationatoms and inhibit bond formation

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EnergyEnergy

The ability to do The ability to do workwork Work -- Work -- force on an object that causes force on an object that causes

it to moveit to move What’s moving?What’s moving?

Two kinds of energyTwo kinds of energy KineticKinetic Potential – can be Potential – can be positionalpositional

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The two fundamental typesThe two fundamental types Kinetic -- Kinetic -- energy of movementenergy of movement

o Heat (thermal energy) -- random Heat (thermal energy) -- random movement of atoms or moleculesmovement of atoms or molecules

Potential -- Potential -- stored energy (can be stored energy (can be because of location!)because of location!)

o Chemical energy -- available for release Chemical energy -- available for release in a chemical reactionin a chemical reaction

What Is Energy?What Is Energy?

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Overview: The Energy of Overview: The Energy of LifeLife

Living cell -- miniature chemical Living cell -- miniature chemical factory factory

Energy transformed and storedEnergy transformed and storedEnergy observed in many formsEnergy observed in many forms

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The Laws of Energy The Laws of Energy TransformationTransformation

Thermodynamics -- study of energy Thermodynamics -- study of energy transformationstransformations Describe availability & usefulness of energyDescribe availability & usefulness of energy

Closed system -- isolated from its Closed system -- isolated from its surroundingssurroundings

Open system -- energy and matter can Open system -- energy and matter can be transferred between the system and be transferred between the system and its surroundingsits surroundings

An open hydroelectric system

G < 0

G = 0

A closed hydroelectric system

G < 0

Closed and open hydroelectric systems can serve as analogiesClosed and open hydroelectric systems can serve as analogies

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Laws of ThermodynamicsLaws of ThermodynamicsFirst -- First -- In any process, the total energy In any process, the total energy

of the universe remains constant.of the universe remains constant. Principle of conservation of energyPrinciple of conservation of energy Energy can be transferred and Energy can be transferred and

transformedtransformed Energy Energy cannotcannot be created or destroyed be created or destroyed

Second -- The entropy of an isolated Second -- The entropy of an isolated system not in equilibrium will tend to system not in equilibrium will tend to increase over time, approaching a increase over time, approaching a maximum value at equilibrium. maximum value at equilibrium. During every energy transfer or During every energy transfer or

transformation, energy is transformation, energy is ““lostlost”” (the amount of (the amount of useable energy decreases; disorder increases)useable energy decreases; disorder increases)

ThermodynamicsThermodynamics

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EntropyEntropyEntropy – randomnessEntropy – randomness

Energy conversions increase entropy in Energy conversions increase entropy in the universethe universe

Spontaneous processes increase Spontaneous processes increase entropyentropy Explosions; car rustingExplosions; car rusting

Non-spontaneous process – energy Non-spontaneous process – energy inputinput Rocks rolling uphillRocks rolling uphill

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EnthalpyEnthalpyEnthalpy (H) – total potential energy of Enthalpy (H) – total potential energy of

systemsystem Total energy = Usable Energy + Unusable EnergyTotal energy = Usable Energy + Unusable Energy

Entropy (S) – randomness or disorder Entropy (S) – randomness or disorder (unusable energy)(unusable energy)

Free Energy (G) – energy available to do workFree Energy (G) – energy available to do work ΔΔG -- change in free energyG -- change in free energy ΔΔG = G = ΔΔGGfinalfinal – – ΔΔGGinitialinitial

A negative A negative ΔΔG – spontaneousG – spontaneous

Note – as entropy increases, free energy Note – as entropy increases, free energy decreasesdecreases

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Free Energy & StabilityFree Energy & Stability

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Exergonic ReactionsExergonic Reactions Exergonic reactionsExergonic reactions release release

energyenergy Reactants contain more energy than Reactants contain more energy than

productsproducts

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Exergonic ReactionsExergonic Reactions Exergonic reactionsExergonic reactions release release

energyenergy Reactants contain more energy than Reactants contain more energy than

productsproducts

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Endergonic ReactionsEndergonic ReactionsEndergonic reactions require an input Endergonic reactions require an input

of energyof energy Products contain more energy than Products contain more energy than

reactantsreactants

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Endergonic ReactionsEndergonic ReactionsEndergonic reactions require an input Endergonic reactions require an input

of energyof energy Products contain more energy than Products contain more energy than

reactantsreactants

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Coupled ReactionsCoupled Reactions

Exergonic reactions drive Exergonic reactions drive endergonic reactionsendergonic reactions The product of an energy-yielding The product of an energy-yielding

reaction fuels an energy-requiring reaction fuels an energy-requiring reaction in a reaction in a coupled reactioncoupled reaction

The parts of coupled reactions often The parts of coupled reactions often occur at different places within the occur at different places within the cellcell

Energy-carrier moleculesEnergy-carrier molecules transfer transfer the energy within cellsthe energy within cells

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ATP powers cellular work ATP powers cellular work by coupling exergonic by coupling exergonic

reactions to endergonic reactions to endergonic reactionsreactions

Cells do work:Cells do work: MechanicalMechanical TransportTransport ChemicalChemical

Cells manage energy resources by Cells manage energy resources by energy coupling: the use of an exergonic energy coupling: the use of an exergonic process to drive an endergonic oneprocess to drive an endergonic one

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The Structure and The Structure and Hydrolysis of ATPHydrolysis of ATP

ATP (adenosine triphosphate) -- cell’s ATP (adenosine triphosphate) -- cell’s energy shuttleenergy shuttle

ATP provides energy for cellular ATP provides energy for cellular functionsfunctions

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Hydrolysis of ATPHydrolysis of ATP High energy phosphate bonds -- broken by High energy phosphate bonds -- broken by

hydrolysishydrolysis Energy release -- chemical change to a state of Energy release -- chemical change to a state of

lower free energy, not from the phosphate lower free energy, not from the phosphate bonds themselvesbonds themselves

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Energy from ATP hydrolysis can be used Energy from ATP hydrolysis can be used to drive an endergonic reactionto drive an endergonic reaction

Overall, the coupled reactions are Overall, the coupled reactions are exergonicexergonic

NH2

Glu

Pi

Pi

Pi

Pi

Glu NH3

P

P

P

ATPADP

Motor proteinMechanical work: ATP phosphorylates motor proteins

Protein moved

Membraneprotein

Solute

Transport work: ATP phosphorylates transport proteins

Solute transported

Chemical work: ATP phosphorylates key reactants

Reactants: Glutamic acidand ammonia

Product (glutamine)made

+ +

+

PhosphorylationPhosphorylation

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The Regeneration of ATPThe Regeneration of ATP

ATP -- renewable resource ATP -- renewable resource regenerated by addition of a phosphate regenerated by addition of a phosphate

group to ADPgroup to ADPThe energy comes from catabolic The energy comes from catabolic

reactions in the cellreactions in the cellThe potential energy stored in ATP The potential energy stored in ATP

drives most cellular workdrives most cellular work

LE 8-12LE 8-12

Pi

ADP

Energy for cellular work(endergonic, energy-consuming processes)

Energy from catabolism(exergonic, energy-yielding processes)

ATP

+

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Exergonic ReactionsExergonic Reactions Exergonic reactionsExergonic reactions release release

energyenergy Spontaneous?Spontaneous?

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The Activation Energy The Activation Energy BarrierBarrier

Chemical reactions -- bond breaking and Chemical reactions -- bond breaking and bond formingbond forming

The initial energy -- free energy of The initial energy -- free energy of activation, or activation energy (Eactivation, or activation energy (EAA) )

EEAA often supplied in the form of heat often supplied in the form of heat from the surroundingsfrom the surroundings

LE 8-14LE 8-14

Transition state

C D

A B

EA

Products

C D

A B

G < O

Progress of the reaction

Reactants

C D

A B

Fre

e e

nerg

y

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How Enzymes Catalyze How Enzymes Catalyze ReactionsReactions

Lowering Energy of Activation (ELowering Energy of Activation (EAA)) Enzymes do not affect the change in Enzymes do not affect the change in

free-energyfree-energy hasten reactions that would occur eventuallyhasten reactions that would occur eventually

Biological catalystsBiological catalysts Specific for the molecules they catalyzeSpecific for the molecules they catalyze Activity often enhanced or suppressed by Activity often enhanced or suppressed by

their reactants or productstheir reactants or products

LE 8-15LE 8-15

Course ofreactionwithoutenzyme

EA

without enzyme

G is unaffectedby enzyme

Progress of the reaction

Fre

e e

nerg

y

EA withenzymeis lower

Course ofreactionwith enzyme

Reactants

Products

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CatalystsCatalysts Catalyst -- chemical agent that speeds up Catalyst -- chemical agent that speeds up

a reaction without being consumed by a reaction without being consumed by the reactionthe reaction

Enzyme -- catalytic proteinEnzyme -- catalytic protein Example: Hydrolysis of sucrose by Example: Hydrolysis of sucrose by

sucrasesucrase

SucroseC12H22O11

GlucoseC6H12O6

FructoseC6H12O6

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Enzymes are a type of protein that acts as a Enzymes are a type of protein that acts as a catalyst, speeding up chemical reactionscatalyst, speeding up chemical reactions

EnzymesEnzymes

Substrate(sucrose)

Enzyme(sucrose)

Fructose

Glucose

Enzymes can Enzymes can perform their perform their functions functions repeatedly, repeatedly, functioning as functioning as workhorses workhorses that carry out that carry out the processes the processes of lifeof life

LE 8-17LE 8-17

Enzyme-substratecomplex

Substrates

Enzyme

Products

Substrates enter active site; enzymechanges 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 EA

and speed up a reaction by• acting as a template for substrate orientation,• stressing the substrates and stabilizing the transition state,• providing a favorable microenvironment,• participating directly in the catalytic reaction.

Substrates areconverted intoproducts.

Products arereleased.

Activesite is

availablefor two new

substratemolecules.

LE 8-18LE 8-18An enzyme’s An enzyme’s activity can activity can be affected be affected by:by: General General

environmental environmental factorsfactors

o temperaturetemperatureo pHpH

Chemicals that Chemicals that specifically specifically influence the influence the enzymeenzyme

Optimal temperature fortypical human enzyme

Optimal temperature forenzyme of thermophilic (heat-tolerant bacteria)

Temperature (°C)

Optimal temperature for two enzymes

0 20 40 60 80 100

Rate

of

reacti

on

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

pH

Optimal pH for two enzymes

0

Rate

of

reacti

on

1 2 3 4 5 6 7 8 9 10

LE 8-19LE 8-19 Competitive -- Competitive --

bind to the active bind to the active site of an enzymesite of an enzyme

Noncompetitive -- Noncompetitive -- bind to another bind to another part of an enzymepart of an enzyme changes shape changes shape makes active site makes active site

less effectiveless effective

Substrate

Active site

Enzyme

Competitiveinhibitor

Normal binding

Competitive inhibition

Noncompetitive inhibitor

Noncompetitive inhibition

A substrate canbind normally to the

active site of anenzyme.

A competitiveinhibitor mimics the

substrate, competingfor the active site.

A noncompetitiveinhibitor binds to the

enzyme away from theactive site, altering the

conformation of theenzyme so that its

active site no longerfunctions.

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Regulation of enzyme Regulation of enzyme activity helps control activity helps control

metabolismmetabolism

Chemical chaos -- if cell’s metabolic Chemical chaos -- if cell’s metabolic pathways were pathways were notnot tightly regulated tightly regulated

Cells switch genes on or off that Cells switch genes on or off that encode specific enzymesencode specific enzymes

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Allosteric Regulation of Allosteric Regulation of EnzymesEnzymes

Enzymes -- active and inactive Enzymes -- active and inactive formsforms The binding of activator -- stabilizes The binding of activator -- stabilizes

the active formthe active form The binding of an inhibitor -- stabilizes The binding of an inhibitor -- stabilizes

the inactive formthe inactive form

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LE 8-20aLE 8-20aAllosteric enzymewith four subunits

Regulatorysite (oneof four)

Active form

Activator

Stabilized active form

Active site(one of four)

Allosteric activatorstabilizes active form.

Non-functionalactive site

Inactive formInhibitor

Stabilized inactive form

Allosteric inhibitorstabilizes inactive form.

Oscillation

Allosteric activators and inhibitors

function function affected by affected by binding of a binding of a regulatory regulatory molecule at molecule at anotheranother site site

Allosteric Allosteric regulationregulation

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Allosteric RegulationAllosteric RegulationCooperativity -- can amplify enzyme activityCooperativity -- can amplify enzyme activity

Substrate

Binding of one substrate molecule toactive site of one subunit locks allsubunits in active conformation.

Cooperativity another type of allosteric activation

Stabilized active formInactive form

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Feedback Feedback InhibitionInhibition

End product of a End product of a metabolic metabolic pathway shuts pathway shuts down the down the pathwaypathway

Intermediate A

Isoleucineused up bycell

Feedbackinhibition Active site of

enzyme 1 can’tbindtheoninepathway off

Isoleucinebinds toallostericsite

Intermediate B

Intermediate C

Intermediate D

End product(isoleucine)