Ch 8 Cellular Metabolism How cells utilize energy

Ch 8 Cellular MetabolismHow cells utilize energy

LE 8-2On the platform,the diver hasmore potentialenergy.

Diving convertspotentialenergy to kinetic energy.

Climbing up convertskinetic energy ofmuscle movement topotential energy.

In the water, the diver has lesspotential energy.

LE 8-3

Chemical energy

Heat CO2

First law of thermodynamics Second law of thermodynamics

H2O

The First Law of Thermodynamics

– Energy cannot be created or destroyed – Energy can be transferred and transformed

Principle of conservation of energy

The Second Law of Thermodynamics

• Every energy transfer or transformation increases the entropy (disorder) of the universe

• Because some energy is lost as heat (unusable)

• Metabolism– an organism’s (or cell’s) total chemical reactions

Name a common cellular reaction.

Two kinds of reactions:

Catabolism (catabolic rxn)

Breakdown of a larger molecule into smaller lower energy productsReleases of energyExergonic rxn

Anabolism (anabolic rxn)Synthesis of larger high energy molecules fromlower energy reactantsRequires input of energyEndergonic reactions

LE 8-12

Pi

ADP

Energy for cellular work

(endergonic, energy-

consuming processes)

Energy from catabolism

(exergonic, energy-

yielding processes)

ATP

+

Cellular energy used for:transport (across membranes)mechanical work (motility, contraction)enzymatic activity (catalysis of reactions)

Catabolic rxn

C6H12O6 + 6O2 ----> 6CO2 + 6H2O + ATPglucose

Exergonic

Anabolic rxn

6CO2 + 6H2O ----> C6H12O6 + 6O2

glucose

Endergonic

Light

Examples

Biological rxns

-Catalyzed by enzymes

-Often arranged in multiple steps called pathways

LE 8-UN141

Enzyme 1

A B

Reaction 1

Enzyme 2

C

Reaction 2

Enzyme 3

D

Reaction 3

ProductStarting

molecule

Enzymatic Pathway

Enzymes

Biological catalysts

Increase rate of reactionsby lowering activation energy (EA)

Spontaneous reactions can take a long time!Need enzymes to speed reactions for cell survival

Activation Energy (EA)

• Needed to destabilize bonds of reactants

LE 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 en

erg

y

Could raise temp.to break bonds

Why don’t cells rely on increases in temperature to break bonds?

Denaturation of proteins and damage to the cell.

LE 8-15

Course ofreactionwithoutenzyme

EA

without enzyme

G is unaffectedby enzyme

Progress of the reaction

Fre

e en

erg

y

EA withenzymeis lower

Course ofreactionwith enzyme

Reactants

Products

LE 8-13

SucroseC12H22O11

GlucoseC6H12O6

FructoseC6H12O6

Example:

Structure & Function of Enzyme DRAW

• Enzymes bind substrate molecules (the reactant)

• Substrates bind to active site on enzyme

• Binding induces conformational change in enzyme--better ”fit” for substrate

• Active sites are highly specific and discriminatory i.e. sucrase does not accept lactose

LE 8-16

Substrate

Active site

Enzyme Enzyme-substratecomplex

How does enzyme lower activation energy of reaction?

– Orients substrates for optimal interaction

–Strains substrate bonds

–Provides a favorable microenvironment

-Covalently bonds to the substrate

LE 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.

How do we know when a reaction is exergonic or endergonic?

Measure the system’s ability to perform work (usable energy)at uniform temperature and pressure.

Change in Gibbs free energy (G)

G= H-TS

Where H= change in total energy of the system, or enthalpy

T=absolute temperature in Kelvin (oC+273)

S =change in entropy (a measure of disorder)

Another way to think about the state of energy in a cell is before and after a particular reaction occurs

G = G final state - G initial state

If the reaction gives final products that have less energy than the initial reactants, is G negative or positive?

The reverse?

When G < 0, the reaction is exergonic and spontaneous.

When G > 0, the reaction is endergonic and not spontaneous.

(products) (reactants)

LE 8-6a

Reactants

Energy

Products

Progress of the reaction

Amount ofenergy

released(G < 0)

Fre

e en

erg

y

Exergonic reaction: energy released

Catabolic rxn

C6H12O6 + 6O2 ----> 6CO2 + 6H2O + ATPglucose

LE 8-6b

ReactantsEnergy

Products

Progress of the reaction

Amount ofenergy

required(G > 0)

Fre

e en

erg

y

Endergonic reaction: energy required

Anabolic rxn

6CO2 + 6H2O ----> C6H12O6 + 6O2

glucose

Light

Relationship among Free Energy, Instability, and Equilibrium

• Free energy:– 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 (G=0)

• If the metabolism of a cell is at equilibrium, what has occurred?

RIP

LE 8-12

Pi

ADP

Energy for cellular work

(endergonic, energy-

consuming processes)

Energy from catabolism

(exergonic, energy-

yielding processes)

ATP

+

Cellular energy used for:transport (across membranes)mechanical work (motility, contraction)enzymatic activity (catalysis of reactions)

ATP structure

• ATP– adenosine triphosphate

• cellular energy carrier

LE 8-8

Phosphate groups

Ribose (sugar)

Adenine (base)

ATP structure Adenosine triphosphate

Cellular energy currency

LE 8-9

Adenosine triphosphate (ATP)

Energy

P P P

PPP i

Adenosine diphosphate (ADP)Inorganic phosphate

H2O

+ +

• Terminal phosphate bond (ATP--> ADP + Pi)– Hydrolysis of “high energy” phosphate bond

• Energy is released (exergonic)• ADP lower energy than ATP• Why?

• Is ADP more stable than ATP? Explain.

LE 8-8

Phosphate groups

Ribose

Adenine

• Energy from ATP hydrolysis – drives endergonic reactions

• Overall, coupled reactions are exergonic

LE 8-10

Endergonic reaction: G is positive, reactionis not spontaneous

Exergonic reaction: G is negative, reactionis spontaneous

G = +3.4 kcal/mol

G = –7.3 kcal/mol

G = –3.9 kcal/mol

NH2

NH3Glu Glu

Glutamicacid

Coupled reactions: Overall G is negative;together, reactions are spontaneous

Ammonia Glutamine

ATP H2O ADP P i

+

+ +

How ATP Performs Work• Inorganic phosphate from ATP hydrolysis

– Transferred to target molecule• Called phosphorylation • Creates highly reactive, unstable target molecule• More prone to do “work” or change (conformation)

– Mechanical, transport, enzymatic

LE 8-11

NH2

Glu

P i

P i

P i

P i

Glu NH3

P

P

P

ATPADP

Motor protein

Mechanical 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

+ +

+

Regeneration of ATP

• ADP + P i--> ATP

– Energy for ADP phosphorylation from catabolic reactions

LE 8-12

Pi

ADP

Energy for cellular work

(endergonic, energy-

consuming processes)

Energy from catabolism

(exergonic, energy-

yielding processes)

ATP

+

Environmental Conditions Affect Enzyme Function

?

Temperature: cold-->decreased chance of bumping into substratehot--> good chance of substrate interaction but

chance of denaturation at some point

pH->change in charge (H+ or OH-) can denature proteins and substrate

Examples of pH sensitive enzymes?

LE 8-18

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

Ra

te o

f re

ac

tio

n

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

pH

Optimal pH for two enzymes

0

Ra

te o

f re

ac

tio

n

1 2 3 4 5 6 7 8 9 10

What isyournormalbodytemp.?

Cofactors• Non-protein enzyme helpers (like metals (Fe))

•Coenzymes•organic cofactors

•Vitamins •e.g. Vitamin K: required for blood clotting &

Required in certain carboxylation reactions

Regulation of EnzymesEnzyme Inhibitors

• Competitive inhibitor– binds to active site of enzyme– blocks substrate binding by competition

•Noncompetitive inhibitor– binds to another part of enzyme– causes enzyme to change shape– prevents active site from binding substrate–Allosteric effect

DRAW

LE 8-19Substrate

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.

Allosteric Regulation of Enzymes

• Where protein function at one site is affected by binding of a regulatory molecule at another site

• May inhibit or stimulate enzyme activity

Allosteric Activation and Inhibition

• Most allosterically regulated enzymes are made from polypeptide subunits

• active and inactive forms

• binding of activator stabilizes active form of enzyme

• binding of inhibitor stabilizes inactive form of enzyme

LE 8-20a

Allosteric 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

• Cooperativity– form of allosteric regulation that can amplify enzyme

activity

• binding of substrate to one active site stabilizes favorable conformational changes at all other subunits

LE 8-20b

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

Feedback Inhibition

• End product of a metabolic pathway shuts down the pathway

• Prevents over-production of unneededmolecules

LE 8-21

Active siteavailable

Initial substrate(threonine)

Threoninein active site

Enzyme 1(threoninedeaminase)

Enzyme 2

Intermediate A

Isoleucineused up bycell

Feedbackinhibition Active site of

enzyme 1 can’tbindtheoninepathway off

Isoleucinebinds toallostericsite

Enzyme 3

Intermediate B

Enzyme 4

Intermediate C

Enzyme 5

Intermediate D

End product(isoleucine)

Metabolic regulation influenced by cellular localization

• Cellular structures organize and concentrate enzymes in pathways– Membranes, organelles (mitochondria, chloroplast)

LE 8-22

Mitochondria,sites of cellular respiration

1 µm

LE 8-22

It’s nice to get so much attention!