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MetabolismandEnergyBIOL222

Ch.8

Metabolism

•  Metabolism

•  Thetotalityofanorganism’s

chemicalreac:ons

•  Sumofanabolismand

catabolism

•  emergentpropertyoflifethat

arisesfrominterac:ons

betweenmoleculeswithinthe

cell

•  Butinacontrolledmanner…

•  homeostasis

MetabolicPathways

•  Metabolicpathway

•  beginswithaspecificmolecule

•  andendswithaspecific

product

•  Eachstepiscatalyzedbyaspecific

enzyme

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•  Catabolicpathways

•  Releaseenergybybreakingdowncomplexmoleculesintosimplercompounds

•  Cellularrespira9on

•  Thebreakdownofglucoseinthepresenceofoxygen

•  Anabolicpathways

•  Consumeenergytobuildcomplexmoleculesfromsimplerones

•  Ie-Thesynthesisofproteinfromaminoacids

•  Bioenerge9cs

•  Thestudyofhoworganismsmanagetheirenergyresources

•  Alllifeboilsdowntoenergybudget

Catabolism

•  Kine9cenergy

•  energyassociatedwithmo:on

•  Heat(thermalenergy)

•  kine:cenergyassociatedwithrandommovementofatomsormolecules

•  Poten9alenergy

•  energythatmaKerpossessesbecauseofitsloca:onorstructure

•  Chemicalenergy

•  poten:alenergyavailableforreleaseinachemicalreac:on

•  Energycanbeconvertedfromoneformtoanother

TypesofEnergy

TheLawsofEnergyTransforma9on

•  Thermodynamics

•  Thestudyofenergytransforma:ons

•  Closedsystem

•  Isolatedfromitssurroundings

•  Liquidinathermos

•  Opensystem

•  EnergyandmaKercanbetransferredbetweenthesystemanditssurroundings

•  Organismsareopensystems

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TheFirstLawofThermodynamics•  Firstlawofthermodynamics(LawofConserva:onofEnergy)

•  Theenergyoftheuniverseisconstant:

–Energycannotbecreatedordestroyedbuttransferredand/ortransformed

TheSecondLawofThermodynamics•  Secondlawofthermodynamics:

–Everyenergytransferortransforma5onincreasestheentropy(disorder)oftheuniverse

•  Duringeveryenergytransferortransforma:on

•  Someenergyisunusable,oRenlostasheat

•  Increasesentropy

•  Livingcellsunavoidablyconvertorganizedforms

ofenergytoheat

•  2ndlaw

•  Spontaneousprocessesoccurwithoutenergy

input

•  canhappenquicklyorslowly

•  tooccurwithoutenergyinput

•  mustincreasetheentropyofthe

universe

•  Generallycorrespondstobreakdown

Energy

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BiologicalOrderandDisorder•  Cells

•  Createorderedstructuresfromlessorderedmaterials

•  Anabolism

•  Equalslessentropy

•  Requirestheinputofenergy

•  Cells

•  AlsoreplaceorderedformsofmaKerandenergywithlessorderedforms

•  Catabolism

•  Energyflowsintoanecosystemintheformoflightandexitsintheformofheat

•  Evolu:on

•  Yieldsmorecomplexorganisms

•  Doesnotviolatethesecondlawofthermodynamics

•  Entropy(disorder)maydecreaseinanorganism

•  buttheuniverse’stotalentropyincreases

OrganismalOrder

Free-EnergyChange(ΔG)•  Needtoknowwhichreac:onsoccurspontaneouslyand

whichrequireinputofenergy

•  needtodetermineenergychangesthatoccurin

chemicalreac:ons

•  Enthalpy(H)

•  Ameasureofthetotalenergyofathermodynamic

system(includingvolumeandpressure)

•  Notactuallymeasurable

•  Insteadmeasurehowmuchenergyis

releasedorabsorbed

•  (Gibbs)Freeenergy(G)

•  Alivingsystem’senergyavailabletodoworkwhen

temperatureandpressureareuniform

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•  (Gibbs)Freeenergychange

•  (∆G):ChangeinGibbsfreeenergyduringachemicalreac:on

•  (∆H):Changeinenthalpy(totalenergyinbiologicalsystems)

•  (∆S):Changeinentropy(disorder)

•  (T):temperatureinKelvin

•  ∆G=∆H–T∆S

•  Onlyprocesseswithanega:ve∆Garespontaneous

•  Releaseenergy

•  Spontaneousprocessescanbeharnessedtoperformwork

Free-EnergyChange(ΔG)

FreeEnergy,Stability,andEquilibrium•  Therefore,freeenergy

•  measureofasystem’sinstability,itstendencytochangetoamore

stablestate

•  Duringspontaneouschange

•  freeenergydecreasesandthestabilityofasystemincreases

•  Equilibrium

•  stateofmaximumstability

•  Lowestenergy

•  Aprocessisspontaneousandcanperformworkonlywhenitismoving

towardequilibrium

ExergonicandEndergonicReac9onsinMetabolism•  Freeenergychangesinreac:ons

•  Exergonicreac9on

•  proceedswithanetreleaseoffree

energyandisspontaneous

•  Resultsinlowerenergy,morestable

products

•  Endergonicreac9on

•  absorbsfreeenergyfromits

surroundingsandis

nonspontaneous

•  Resultsinhigherenergy,lessstable

products

Energy

(a) Exergonic reaction: energy released

Progress of the reaction

Free

ene

rgy

Products

Amount of energy

released (∆G < 0)

Reactants

Energy

(b) Endergonic reaction: energy required

Progress of the reaction

Free

ene

rgy

Products

Amount of energy

required (∆G > 0)

Reactants

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EquilibriumandMetabolism

•  Closedsystems

•  eventuallyreachequilibriumandthen

donomorework

•  Cellsareopensystems

•  Therefore,notinequilibrium

•  Experiencingaconstantflowof

materials

•  Metabolismisneveratequilibrium

•  Adefiningfeatureoflife

•  Acatabolicpathwayinacellreleasesfree

energyinaseriesofreac:ons

(a) An isolated hydroelectric system

∆G < 0 ∆G = 0

(b) An open hydroelectric system ∆G < 0

∆G < 0 ∆G < 0

∆G < 0

(c) A multistep open hydroelectric system

CoupledReac9ons•  Acelldoesthreemainkindsofwork:

•  Chemical

•  Forcedendergonicrxns

•  Monomers->polymers

•  Transport

•  Ac:vetransport

•  Acrosscellmembraneagainstconcentra:ongradients

•  Mechanical

•  Movement

•  Musclecontrac:on,bea:ngofflagellaorcilia

•  Energycoupling

•  Cellsuseenergyofanexergonicprocesstodriveanendergonicone

•  MostenergycouplingincellsismediatedbyATP

TheStructureandHydrolysisofATP

Phosphate groups Ribose

Adenine

•  ATP(adenosinetriphosphate)

•  Energycurrencyofthecell

•  composedof

•  ribose(asugar)

•  adenine(anitrogenousbase)

•  threephosphategroups

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TheStructureandHydrolysisofATP

Inorganic phosphate

Energy

Adenosine triphosphate (ATP)

Adenosine diphosphate (ADP)

P P

P P P

P + +

H2O

i

•  Harves:ngpowerfromATP

•  Breakhighenergyphosphatebonds

•  Byhydrolysis

•  Energyreleasedwhenterminal

phosphatebondisbroken

•  Releaseofenergycomesfromchemical

changetostateoflowerfreeenergy

•  notfromthephosphatebonds

themselves

Fig.8-10

(b) Coupled with ATP hydrolysis, an exergonic reaction

Ammonia displaces the phosphate group, forming glutamine.

(a) Endergonic reaction

(c) Overall free-energy change

P P

Glu NH3

NH2

Glu i

Glu ADP +

P ATP +

+

Glu

ATP phosphorylates glutamic acid, making the amino acid less stable.

Glu NH3

NH2

Glu +

Glutamic acid

Glutamine Ammonia

∆G = +3.4 kcal/mol

+ 2

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•  Phosphoryla9on

•  transferringaphosphategrouptoanothermolecule,suchasareactant

•  Performedbykinases

•  Drivesendergonicreac:ons

•  Therecipientmoleculeisnowphosphorylated

•  Changesahydrophobicregiontohydrophilic

ATP

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Fig.8-11

(b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed

Membrane protein

P i

ADP +

P

Solute Solute transported

P i

Vesicle Cytoskeletal track

Motor protein Protein moved

(a) Transport work: ATP phosphorylates transport proteins

ATP

ATP

Enzymeslowerenergybarriers

•  Catalyst

•  Chemicalagentthatspeedsupa

reac:onwithoutbeing

consumedbythereac:on

•  Enzyme

•  Cataly:cprotein

•  Ex.Hydrolysisofsucrosebythe

enzymesucrase

Sucrose (C12H22O11)

Glucose (C6H12O6) Fructose (C6H12O6)

Sucrase

TheAc9va9onEnergyBarrier

•  Everychemicalreac:onbetween

moleculesinvolvesbondbreakingand

bondforming

•  Ac9va9onenergy(EA),orfreeenergy

ofac9va9on

•  Theini:alenergyneededto

startachemicalreac:on

•  ORensuppliedintheform

ofheatfromthe

surroundings

Progress of the reaction

Products

Reactants

∆G < O

Transition state

Free

ene

rgy

EA

D C

B A

D

D

C

C

B

B

A

A

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HowEnzymesLowertheEABarrier

•  Enzymescatalyzereac:onsbyloweringtheEAbarrier

•  donotaffectthechangeinfreeenergy(∆G)

•  Insteadhastenreac:onsthatwouldoccureventually

Progress of the reaction

Products

Reactants

∆G is unaffected by enzyme

Course of reaction without enzyme

Free

ene

rgy

EA without enzyme EA with

enzyme is lower

Course of reaction with enzyme

SubstrateSpecificityofEnzymes•  Substrate

•  Thereactantthatanenzymeactson

•  Theenzymebindstoitssubstrate,forminganenzyme-substratecomplex

•  Ac9vesite

•  regionontheenzymewherethesubstratebinds

•  Inducedfit

•  enzyme-substratecomplextriggersconforma:onalchangeinenzyme

•  bringschemicalgroupsoftheac:vesiteintoposi:onsthatenhancetheirabilitytocatalyzethereac:on

•  Bycontor:ngandstressingbondsinsubstrate

Substrate

Active site

Enzyme Enzyme-substrate complex

(b) (a)

CatalysisintheEnzyme’sAc9veSite

Substrates

Enzyme

Products are released.

Products

Substrates are converted to products.

Active site can lower EA and speed up a reaction.

Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds.

Substrates enter active site; enzyme changes shape such that its active site enfolds the substrates (induced fit).

Active site is

available for two new

substrate molecules.

Enzyme-substrate complex

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3

2 1

6

4

•  Theac:vesitecanloweranEAbarrierby

•  Orien:ngsubstratescorrectly

•  Strainingsubstratebonds

•  Providingafavorablemicroenvironment

•  Covalentlybondingtothesubstrate

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EffectsofTemperatureandpH

•  Eachenzymehas

•  Anop:maltemperatureforfunc:on

•  Taqpolymeraseat~78°C

•  Anop:malpHforfunc:on

•  Pepsinogen/pepsinatpH2

•  Notnecessarilythesameforallenzymes

Rat

e of

reac

tion

Optimal temperature for enzyme of thermophilic

(heat-tolerant) bacteria

Optimal temperature for typical human enzyme

(a) Optimal temperature for two enzymes

(b) Optimal pH for two enzymes

Rat

e of

reac

tion

Optimal pH for pepsin (stomach enzyme)

Optimal pH for trypsin (intestinal enzyme)

Temperature (ºC)

pH 5 4 3 2 1 0 6 7 8 9 10

0 20 40 80 60 100

Cofactors

•  Cofactors

•  nonproteinenzymehelpers

•  maybeinorganic(suchasametalinionicform)ororganic

•  Coenzyme

•  organiccofactor

•  includevitamins

•  Ie-VitaminC-ascorbicacid

EnzymeInhibitors

(a) Normal binding (c) Noncompetitive inhibition (b) Competitive inhibition Noncompetitive inhibitor

Active site Competitive inhibitor

Substrate

Enzyme

•  Compe99veinhibitors

•  bindtotheac:vesiteofanenzyme,compe:ngwiththesubstrate

•  Blockac:vesite

•  Noncompe99veinhibitors

•  bindtoanotherpartofanenzyme

•  causeenzymetochangeshapealteringac:vesite

•  Examplesofinhibitorsincludetoxins,poisons,pes:cides,andan:bio:cs

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AllostericRegula9onofEnzymes•  Allostericregula9on

•  mayeitherinhibitors:mulate

anenzyme’sac:vity

•  occurswhenaregulatory

moleculebindstoaproteinat

onesite

•  andaffectstheprotein’s

func:onatanothersite

•  Canbeaformofnon-

compe55veinhibi5on

AllostericAc9va9onandInhibi9on

•  Mostallostericallyregulatedenzymes

•  aremadefromindividual

polypep:desubunits

•  Eachwithitsownac:vesite

•  Eachenzymehasac:veandinac:ve

forms

•  bindingofanac:vatorstabilizes

theac:veformoftheenzyme

•  bindingofaninhibitorstabilizes

theinac:veformoftheenzyme

(a) Allosteric activators and inhibitors

Inhibitor Non- functional active site

Stabilized inactive form

Inactive form

Oscillation

Activator Active form Stabilized active form

Regulatory site (one of four)

Allosteric enzyme with four subunits

Active site (one of four)

•  Coopera9vity

•  aformofallostericregula:onthatcanamplifyenzymeac:vity

•  bindingbyasubstratetooneac:vesitestabilizesfavorable

conforma:onalchangesatallothersubunits

AllostericRegula9on

(b) Cooperativity: another type of allosteric activation

Stabilized active form

Substrate

Inactive form

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FeedbackInhibi9on

•  Feedbackinhibi9on

•  theendproductofametabolic

pathwayshutsdownthe

pathway

•  Feedbackinhibi:onpreventsacell

fromwas:ngchemicalresourcesby

synthesizingmoreproductthanis

needed

Intermediate C

Feedback inhibition

Isoleucine used up by cell

Enzyme 1 (threonine deaminase)

End product (isoleucine)

Enzyme 5

Intermediate D

Intermediate B

Intermediate A

Enzyme 4

Enzyme 2

Enzyme 3

Initial substrate (threonine)

Threonine in active site

Active site available

Active site of enzyme 1 no longer binds threonine; pathway is switched off.

Isoleucine binds to allosteric site

Youshouldnowbeableto:1.  Dis:nguishbetweenthefollowingpairsofterms:catabolicand

anabolicpathways;kine:candpoten:alenergy;openandclosedsystems;exergonicandendergonicreac:ons

2.  Inyourownwords,explainthesecondlawofthermodynamicsandexplainwhyitisnotviolatedbylivingorganisms

3.  Explainingeneraltermshowcellsobtaintheenergytodocellularwork

4.  ExplainhowATPperformscellularwork

5.  Explainwhyaninvestmentofac:va:onenergyisnecessarytoini:ateaspontaneousreac:on

6.  Describethemechanismsbywhichenzymeslowerac:va:onenergy

7.  Describehowallostericregulatorsmayinhibitors:mulatetheac:vityofanenzyme