MetabolismMetabolism

Cell MetabolismCell Metabolism

2

EnergyEnergy

Energy is the capacity to do work.Energy is the capacity to do work.

A handful of A handful of peanuts contains peanuts contains enough energy to enough energy to boil a quart of boil a quart of waterwater

3

Energy FormsEnergy Forms

Forms of energy:Forms of energy:• Potential energyPotential energy

• Kinetic energyKinetic energy

High potential energy

Conversion ofpotential energyto kinetic energy

Low potential energyConversion of kinetic energy to potential energy

4

Cellular WorkCellular Work

Cells use energy for:Cells use energy for:• Mechanical workMechanical work• Transport workTransport work• Chemical workChemical work

Cellular Work Cellular Work = Metabolism= Metabolism It takes about 10 It takes about 10

million ATP molecules million ATP molecules per second to power per second to power an active muscle cell.an active muscle cell.

5

First Law of ThermodynamicsFirst Law of Thermodynamics

The total amount of The total amount of energy in the universe energy in the universe remains constant.remains constant.

Energy can be Energy can be transformed from one transformed from one form to another, but it form to another, but it cannot be created or cannot be created or destroyed.destroyed.

6

Second Law of ThermodynamicsSecond Law of Thermodynamics

Energy transformations increase entropy Energy transformations increase entropy (degree of disorder) in a closed system.(degree of disorder) in a closed system.– No energy conversion is 100 percent efficient.No energy conversion is 100 percent efficient.

Systems tend to Systems tend to go from states of go from states of higher free energy higher free energy to states of lower to states of lower free energy.free energy.

7

Exergonic ReactionsExergonic Reactions

AA BB

EnergyReleased

CC DD

++

++

High EnergyHigh EnergyReactantsReactants

Low EnergyLow EnergyProductsProductsEnergy is released.

Products have less energy than starting substance.

8

Exergonic ExampleExergonic Example

EnergyReleased

++

++High EnergyHigh EnergyReactantsReactants

Low EnergyLow EnergyProductsProducts

OHO

OCH2OH

O O

O OC

OHH

9

Exergonic Energy DiagramExergonic Energy Diagram

EnergyEnergycontentcontent

ofofmoleculesmolecules

highhigh

lowlow

An exergonic reaction: Burning GlucoseAn exergonic reaction: Burning Glucose

Progress of reactionProgress of reaction

Activation energy neededActivation energy neededto start reactionto start reaction

Activation energy neededActivation energy neededto start reactionto start reaction

Glucose + OGlucose + O22Glucose + OGlucose + O22

Energy Energy releasedreleased by byburning glucoseburning glucose

Energy Energy releasedreleased by byburning glucoseburning glucose

C OC O22 + H + H22OOC OC O22 + H + H22OO

10

Endergonic ReactionsEndergonic Reactions

AA BB++

CC DD++

Low EnergyLow EnergyReactantsReactants

High EnergyHigh EnergyProductsProducts

energyenergy

Energy input is required

Products store more energy

than starting substances.

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Endergonic Energy DiagramEndergonic Energy Diagram

EnergyEnergycontentcontent

ofofmoleculesmolecules

highhigh

lowlow

(b)(b) An endergonic reaction: An endergonic reaction: PhotosynthesisPhotosynthesis

Progress of reactionProgress of reaction

GlucoseGlucoseGlucoseGlucose

Net energyNet energyincreaseincrease by bysynthesizingsynthesizing

glucoseglucose

COCO22 + H + H22OOCOCO22 + H + H22OO

ActivationActivationenergy fromenergy fromlight light storedstored

by by photosynthesisphotosynthesis

12

Endergonic ExampleEndergonic Example

++

Low EnergyLow EnergyReactantsReactants ++

High EnergyHigh EnergyProductsProducts

OHO

OCH2OH

O O

O OC

OHH

EnergySupplied

13

Energy FlowEnergy Flow

Energy flows into ecosystems as sunlight. Energy flows into ecosystems as sunlight. (The sun is life’s primary energy source.)(The sun is life’s primary energy source.)Producers (autotrophs) trap energy from Producers (autotrophs) trap energy from the sun and convert it into chemical bond the sun and convert it into chemical bond energy.energy.All organisms use the energy stored in the All organisms use the energy stored in the bonds of organic compounds to do work.bonds of organic compounds to do work. LIVING SYSTEMS ARE LIVING SYSTEMS ARE NOTNOT CLOSED CLOSED SYSTEMS!SYSTEMS!

14

Energy RelationshipsEnergy Relationships

ATP

BIOSYNTHETIC PATHWAYS

(ANABOLIC)

ENERGY INPUT

DEGRADATIVE PATHWAYS

(CATABOLIC)

energy-poor products(such as carbon dioxide, water)

large energy-rich molecules(fats, complex carbohydrates,

proteins, nucleic acids)

simple organic compounds(simple sugars, amino acids,

fatty acids, nucleotides)

ADP + Pi

Chemical reactions either store or release energy.Chemical reactions either store or release energy.

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The Role of ATPThe Role of ATP

Cells “earn” ATP in exergonic reactions.Cells “earn” ATP in exergonic reactions.

Cells “spend” ATP in endergonic reactions.Cells “spend” ATP in endergonic reactions.

P P P

ribose

adenine

ATP - adenosine triphosphate

16ADP & ATPADP & ATP

OH

PPO

O

O PP OH

OH

O

~~RiboseRibose

HH22CCHH22CC

HHHH

OOOO

HHHH

OHOHOHOHOHOHOHOH

HHHHHHHH

NNNNHCHCHCHC

NNNN CCCC

CCCC

CCCC

CHCHCHCH

NNNN

NNNN

NHNH22NHNH22

AdenineAdenine

Adenosine

Adenosine

PP OH

OH

O

OH

PPO

O

O PP O

OH

O

~~RiboseRibose

HH22CCHH22CC

HHHH

OOOO

HHHH

OHOHOHOHOHOHOHOH

HHHHHHHH

NNNNHCHCHCHC

NNNN CCCC

CCCC

CCCC

CHCHCHCH

NNNN

NNNN

NHNH22NHNH22

AdenineAdenine

Adenosine

Adenosine

~~

DiPhosphateDiPhosphate

TriPhosphateTriPhosphate

ADPADP

ATPATP

High-energyHigh-energyPhosphatePhosphate

BondBond

17

Coupled Reactions: SynthesisCoupled Reactions: Synthesis

18

Coupled Reaction: PhosphorylationCoupled Reaction: Phosphorylation

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Coupled Reactions: Muscle ActionCoupled Reactions: Muscle Action

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Active TransportActive Transport

ATP gives up phosphate ATP gives up phosphate to activate protein.to activate protein.

Binding of ATP changes Binding of ATP changes protein shape and protein shape and affinity for solute.affinity for solute.

P

P

P

P

High solute concentration

Low solute concentration

ATP ADP

21

Electron CarriersElectron Carriers

22

Enzyme ActionEnzyme Action

a. Enzymes speed up metabolic reactions by lowering activation energy.

b. Enzymes are substrate specific.

c. Enzyme activity is regulated by inhibitors.

d. A cell’s physical and chemical environment effects enzyme activity.

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Hydrolysis of SucroseHydrolysis of Sucrose

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Enzymes are CatalystEnzymes are Catalysta. Enzymes speed up metabolic

reactions by lowering activation energy

• A catalyst is a chemical agent that changes the rate of a reaction without being consumed by the reaction.

• An enzyme is a catalytic protein.• Enzymes regulate the movement of

molecules through metabolic pathways.

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““Lowering” Activation EnergyLowering” Activation Energy

A + B

C + D

A B298oK, no catalyst

T, no catalyst298oK, inorganic catalyst298oK, enzyme

Fig. 2

EnergyEnergycontentcontent

ofofmoleculesmolecules

highhigh

lowlow

Progress of reactionProgress of reaction

26

Metabolic PathwaysMetabolic Pathways

AA BB CC DDDD EEEE

FFFF GGGG

Enzyme 1Enzyme 1 Enzyme 2Enzyme 2 Enzyme 3Enzyme 3 Enzyme 4Enzyme 4

Enzyme 5Enzyme 5 Enzyme 6Enzyme 6

InitialInitialReactantsReactants

IntermediatesIntermediates FinalFinalProductsProducts

Pathway 1Pathway 1Pathway 1Pathway 1

Pathway 2Pathway 2Pathway 2Pathway 2

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Enzymes SpecificityEnzymes Specificity

b. Enzymes are substrate specific• A substrate is a reactant which binds to

an enzyme.• When a substrate or substrates binds to

an enzyme, the enzyme catalyzes the conversion of the substrate to the product.

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Enzyme Active SitesEnzyme Active Sites

• The active site of an enzyme is a pocket or groove on the surface of the protein.• The specificity of an enzyme is due to the fit between the active site and the substrate.• As the substrate binds, the enzyme changes shape leading to a tighter induced fit.

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substrate

enzyme

E + S

Induced Fit ModelInduced Fit Model

Fig. 3

initial binding due to e.g., charge interactions

ES*

enzyme-substrate(ES) complex

inductionof fit

ES

enzyme

products

E + Psubstrate contact

with active siteenzyme unchanged

by reaction TRANSITION STATE good orientation but unstable

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Enzyme-Substrate InteractionsEnzyme-Substrate InteractionsSubstrateSubstrateSubstrateSubstrateSubstrateSubstrateSubstrateSubstrate

EnzymeEnzymeEnzymeEnzyme

ActiveActiveSiteSite

ActiveActiveSiteSite

11 Substrates Substrates enter active enter active sitesite

11 Substrates Substrates enter active enter active sitesite

22 Shape change Shape change promotes reactionpromotes reaction

22 Shape change Shape change promotes reactionpromotes reaction

33 Product released;Product released;enzyme ready againenzyme ready again

33 Product released;Product released;enzyme ready againenzyme ready again

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c. Enzyme activity is regulated by inhibitors.

• Some molecules inhibit enzymes from catalyzing reactions.

• If the inhibitor binds to the same site as the substrate, then it blocks substrate binding via competitive inhibition.

• If the inhibitor binds somewhere other than the active site, it blocks substrate binding via noncompetitive inhibition.

32

Negative Feedback ModelsNegative Feedback Models

33

End Product InhibitionEnd Product Inhibition

Prevents excess accumulation of final product.Results in alternative pathway and product.

34

E 5E 5E 5E 5DDDD

E 4E 4E 4E 4CCCC

E 3E 3E 3E 3BBBB

Feedback InhibitionFeedback Inhibition

E 2E 2E 2E 2AAAA

Feedback InhibitionFeedback InhibitionIsoleucine inhibits enzyme 1Isoleucine inhibits enzyme 1

E 1E 1E 1E 1

CHCH33CHCH33

CCCC

CCCC

COOHCOOHCOOHCOOH

OHOHOHOH

NHNH33NHNH33HHHH

HHHHCHCH22

CHCH22

CCCC

CCCC

COOHCOOHCOOHCOOH

CHCH33CHCH33

NHNH33NHNH33HHHH

HHHH

CHCH33CHCH33

ThreonineThreonine(substrate)(substrate)ThreonineThreonine(substrate)(substrate) IsoleucineIsoleucine

(end product)(end product)IsoleucineIsoleucine

(end product)(end product)

35Allosteric Regulation vs. CompetitionAllosteric Regulation vs. Competition

SubstrateSubstrateSubstrateSubstrate

EnzymeEnzymeEnzymeEnzyme

Active Active SiteSite

Active Active SiteSite

Allosteric Allosteric SiteSite

Allosteric Allosteric SiteSite

(a)(a)

Allosteric Allosteric Regulatory Regulatory

MoleculeMolecule

Allosteric Allosteric Regulatory Regulatory

MoleculeMolecule

Shape of activeShape of activesite changedsite changed(b)(b)

(c)(c)

Competitive inhibitorCompetitive inhibitoroccupies active siteoccupies active site

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Effects on Enzyme ActionEffects on Enzyme Action

d. A cell’s physical and chemical environment effects enzyme activity

• The three-dimensional structure of enzymes depend on environmental conditions.

• Changes in shape influence the reaction rate.

• Some conditions lead to the most active conformation and optimal rate of reaction.

37

Effect of pHEffect of pH

• pH influences shape and reaction rate.

• Each enzyme has an optimal pH (usually between pH 6 – 8).

• However, digestive enzymes in the stomach are designed to work best at pH 2 while those in the intestine are optimal at pH 9.

38

Effect of TemperatureEffect of Temperature

• As temperature increases, collisions between substrates and active sites occur more frequently.

• At some point, thermal agitation begins to destabilize the protein’s active conformation and the protein denatures.

• Each enzyme has an optimal temperature.

39

Effect of Cofactors & CoenzymesEffect of Cofactors & Coenzymes

• Many enzymes require nonprotein cofactors for catalytic activity and include zinc, iron, and copper.

• Organic cofactors, coenzymes, include vitamins or molecules derived from vitamins.

40

Effect of Substrate ConcentrationEffect of Substrate Concentration

• The rate of product The rate of product formation increases formation increases as the [substrate] as the [substrate] increases.increases.

• Rate levels when Rate levels when enzyme becomes enzyme becomes saturated.saturated.

• Additional substrate Additional substrate does not not increase does not not increase reaction rate.reaction rate.

MetabolismMetabolism

The endThe end