1 Energy and Metabolism. 2 The Energy of Life The living cell generates thousands of different...

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Energy and Metabolism

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The Energy of Life • The living cell generates thousands of

different reactions• Metabolism

• Is the totality of an organism’s chemical reactions

• Arises from interactions between molecules

• An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics

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Metabolic Pathways• Biochemical pathways are the organizational units of metabolism• Metabolism is the total of all chemical reactions carried out by an

organism• A metabolic pathway has many steps that begin with a specific

molecule and end with a product, each catalyzed by a specific enzyme• Reactions that join small molecules together to form larger, more

complex molecules are called anabolic.• Reactions that break large molecules down into smaller subunits are

called catabolic.

Enzyme 1 Enzyme 2 Enzyme 3

A B C D

Reaction 1 Reaction 2 Reaction 3

Startingmolecule

Product

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Metabolic Pathway• A sequence of chemical reactions, where the product of

one reaction serves as a substrate for the next, is called a metabolic pathway or biochemical pathway

• Most metabolic pathways take place in specific regions of the cell.

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Bioenergetics

• Bioenergetics is the study of how organisms manage their energy resources via metabolic pathways

• Catabolic pathways release energy by breaking down complex molecules into simpler compounds

• Anabolic pathways consume energy to build complex molecules from simpler ones

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Energy

• Energy is the capacity to do work or ability to cause change. Any change in the universe requires energy. Energy comes in 2 forms:• Potential energy is stored energy. No

change is currently taking place• Kinetic energy is currently causing

change. This always involves some type of motion.

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Forms of Energy

• Kinetic energy is the energy associated with motion

• Potential energy• Is stored in the

location of matter• Includes chemical

energy stored in molecular structure

• Energy can be converted from one form to another

On the platform, a diverhas more potential energy.

Diving converts potentialenergy to kinetic energy.

Climbing up converts kinetic

energy of muscle movement

to potential energy.

In the water, a diver has less potential energy.

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Laws of Energy Transformation

• Thermodynamics is the study of energy changes.

• Two fundamental laws govern all energy changes in the universe. These 2 laws are simply called the first and second laws of thermodynamics:

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The First Law of Thermodynamics

• According to the first law of thermodynamics• Energy cannot be created or destroyed• Energy can be transferred and transformed

For example, the chemical (potential) energy in food will be converted to the kinetic energy of the cheetah’s movement

Chemicalenergy

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Second Law of Thermodynamics• The disorder (entropy) in the universe is continuously increasing.

• Energy transformations proceed spontaneously to convert matter from a more ordered, less stable form, to a less ordered, more stable form

• Spontaneous changes that do not require outside energy increase the entropy, or disorder, of the universe

• For a process to occur without energy input, it must increase the entropy of the universe

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• During each conversion, some of the energy dissipates into the environment as heat.

• During every energy transfer or transformation, some energy is unusable, often lost as heat

• Heat is defined as the measure of the random motion of molecules• Living cells unavoidably convert organized forms of energy to heat• According to the second law of thermodynamics, every energy transfer

or transformation increases the entropy (disorder) of the universe

Second Law of Thermodynamics

For example, disorder is added to the cheetah’ssurroundings in the form of heat and the small molecules that are the by-products of metabolism.

Heat co2

H2O+

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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

• 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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Biological Order and Disorder• Living systems

• Increase the entropy of the universe• Use energy to maintain order• A living system’s free energy is energy that can

do work under cellular conditions• Organisms live at the expense of free energy

50µm

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Free Energy

• Free energy (G) is a measure of the amount of energy available to do useful work. It depends on:• The total amount of energy present; this is called

enthalpy (H)• The amount of energy being used for non-useful

work (random molecular motion); this is called entropy (S).

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Free Energy

• In general:

ΔG = ΔH - T ΔS

• Where T represents the temperature in degrees Kelvin and Δ represent “the change in”.

• This means the amount of energy available for useful work (G) equals the total energy present (H) minus the energy that is being wasted on random molecular motion (S).

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Free Energy

• Free energy is the portion of a system’s energy that is able to perform work when temperature and pressure is uniform throughout the system, as in a living cell

• Free energy also refers to the amount of energy actually available to break and subsequently form other chemical bonds

• Gibbs’ free energy (G) – in a cell, the amount of energy contained in a molecule’s chemical bonds (T&P constant)

• Change in free energy - ΔG • Endergonic - any reaction that requires an input of

energy• Exergonic - any reaction that releases free energy

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Exergonic reactions• Reactants have more free energy than the products • Involve a net release of energy and/or an increase in

entropy• Occur spontaneously (without a net input of energy)

Reactants

Products

Energy

Progress of the reaction

Amount ofenergyreleased (∆G <0)

Fre

e e

ne

rgy

(a) Exergonic reaction: energy released

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Endergonic Reactions• Reactants have less free energy than the products• Involve a net input of energy and/or a decrease in

entropy• Do not occur spontaneously

Energy

Products

Amount ofenergyreleased (∆G>0)

Reactants


Fre

e e

ne

rgy

(b) Endergonic reaction: energy required

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Reactant Reactant

Product

Product

ExergonicEndergonic

Energy isreleased.

Energymust besupplied.

En

erg

y s

up

plie

dE

ner

gy

re

lea

sed

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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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 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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Equilibrium and Metabolism• Reactions in a closed system eventually reach equilibrium

(a) A closed hydroelectric system. Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium.

∆G < 0 ∆G = 0

• Cells in our body experience a constant flow of materials in and out, preventing metabolic pathways from reaching equilibrium

(b) An open hydroelectric system. Flowing water keeps driving the generator because intake and outflow of water keep the system from reaching equlibrium.

∆G < 0

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An Analogy For Cellular Respiration – Glucose Catabolism

(c) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucoce is brocken down in a series of exergonic reactions that power the work of the cell. The product of each reaction becomes the reactant for the next, so no reaction reaches equilibrium.

∆G < 0

∆G < 0

∆G < 0

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Energy Coupling

• Living organisms have the ability to couple exergonic and endergonic reactions:

• Energy released by exergonic reactions is captured and used to make ATP from ADP and Pi

• ATP can be broken back down to ADP and Pi, releasing energy to power the cell’s endergonic reactions.

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The Structure and Hydrolysis of ATP

• ATP (adenosine triphosphate)• Is the cell’s energy shuttle• Provides energy for cellular functions

O O O O CH2

H

OH OH

H

N

H H

O

NC

HC

N CC

N

NH2Adenine

RibosePhosphate groups

O

O O

O

O

O

-- - -

CH

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The Structure and Hydrolysis of ATP• Energy is released from ATP when the terminal phosphate

bond is broken

P

Adenosine triphosphate (ATP)

H2O

+ Energy

Inorganic phosphate Adenosine diphosphate (ADP)

PP

P PP i

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Cellular Work

• A cell does three main kinds of work• Mechanical• Transport• Chemical

• Energy coupling is a key feature in the way cells manage their energy resources to do this work

• ATP powers cellular work by coupling exergonic reactions to endergonic reactions

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Energy Coupling - ATP / ADP Cycle• Releasing the third phosphate from ATP to make ADP generates

energy (exergonic):• Linking the phosphates together requires energy - so making ATP from

ADP and a third phosphate requires energy (endergonic), • Catabolic pathways drive the regeneration of ATP from ADP and

phosphate

ATP synthesis from ADP + P i requires energy

ATP

ADP + P i

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

Energy from catabolism(exergonic, energy yieldingprocesses)

ATP hydrolysis to ADP + P i yields energy

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How ATP Performs Work

• ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant

• The recipient molecule is now phosphorylated• The three types of cellular work (mechanical,

transport, and chemical) are powered by the hydrolysis of ATP

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How ATP Performs Work• ATP drives endergonic reactions by phosphorylation, transferring a

phosphate to other molecules - hydrolysis of ATP

(c) Chemical work: ATP phosphorylates key reactants

P

Membraneprotein

Motor protein

P i

Protein moved(a) Mechanical work: ATP phosphorylates motor proteins

ATP

(b) Transport work: ATP phosphorylates transport proteins

Solute

P P i

transportedSolute

GluGlu

NH3

NH2

P i

P i

+ +

Reactants: Glutamic acid and ammonia

Product (glutamine)made

ADP+

P

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Activation Energy• All reactions, both endergonic and exergonic, require an input of energy

to get started. This energy is called activation energy

• The activation energy, EA

• Is the initial amount of energy needed to start a chemical reaction• Activation energy is needed to bring the reactants close together and weaken

existing bonds to initiate a chemical reaction. • Is often supplied in the form of heat from the surroundings in a system.


Fre

e e

ne

rgy


∆G < O

EAA B

C D

Reactants

A

C D

B

Transition state

A B

C D

Products

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Reaction Rates• In most cases, molecules do not have enough

kinetic energy to reach the transition state when they collide.

• Therefore, most collisions are non-productive, and the reaction proceeds very slowly if at all.

• What can be done to speed up these reactions?

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Increasing Reaction Rates• Add Energy (Heat) - molecules move faster so they collide

more frequently and with greater force. • Add a catalyst – a catalyst reduces the energy needed to

reach the activation state, without being changed itself. Proteins that function as catalysts are called enzymes.

Reactant

Product

CatalyzedUncatalyzed

Product

Reactant

Activationenergy

Activationenergy

En

erg

y su

pp

lied

En

erg

y re

leas

ed


Activation Energy and Catalysis

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Enzymes Lower the EA Barrier

• An enzyme catalyzes reactions by lowering the EA barrier


Products

Course of reaction without enzyme

Reactants

Course of reaction with enzyme

EA

withoutenzyme

EA with enzymeis lower

∆G is unaffected by enzymeF

ree

ener

gy

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Enzymes Are Biological Catalysts

• Enzymes are proteins that carry out most catalysis in living organisms.

• Unlike heat, enzymes are highly specific. Each enzyme typically speeds up only one or a few chemical reactions.

• Unique three-dimensional shape enables an enzyme to stabilize a temporary association between substrates.

• Because the enzyme itself is not changed or consumed in the reaction, only a small amount is needed, and can then be reused.

• Therefore, by controlling which enzymes are made, a cell can control which reactions take place in the cell.

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Substrate Specificity of Enzymes• Almost all enzymes are globular proteins with one or more active sites on their

surface.• The substrate is the reactant an enzyme acts on• Reactants bind to the active site to form an enzyme-substrate complex.• The 3-D shape of the active site and the substrates must match, like a lock and key• Binding of the substrates causes the enzyme to adjust its shape slightly, leading to

a better induced fit.• Induced fit of a substrate brings chemical groups of the active site into positions

that enhance their ability to catalyze the chemical reaction• When this happens, the substrates are brought close together and existing bonds

are stressed. This reduces the amount of energy needed to reach the transition state.

Substate

Active site

Enzyme

Enzyme- substratecomplex

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The Catalytic Cycle Of An Enzyme

Substrates

Products

Enzyme

Enzyme-substratecomplex

1 Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).

2 Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.

3 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 substrate bonds and stabilizing the transition state,• providing a favorable microenvironment,• participating directly in the catalytic reaction.

4 Substrates are Converted intoProducts.

5 Products areReleased.

6 Active siteIs available fortwo new substrateMole.

Figure 8.17

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1 The substrate, sucrose, consistsof glucose and fructose bonded together.

Bond

Enzyme

Active site

The substrate binds to the enzyme, forming an enzyme-substrate complex.

2

H2O

The binding of the substrate and enzyme places stress on the glucose-fructose bond, and the bond breaks.

3

Glucose Fructose

Products are released, and the enzyme is free to bind other substrates.

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The Catalytic Cycle Of An Enzyme

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Factors Affecting Enzyme Activity

• Temperature - rate of an enzyme-catalyzed reaction increases with temperature, but only up to an optimum temperature.

• pH - ionic interactions also hold enzymes together.

• Inhibitors and Activators

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Effects of Temperature and pH

• Each enzyme has an optimal temperature in which it can function

Optimal temperature for enzyme of thermophilic

Rat

e o

f re

actio

n

0 20 40 80 100Temperature (Cº)

(a) Optimal temperature for two enzymes

Optimal temperature fortypical human enzyme

(heat-tolerant) bacteria

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Effects of Temperature and pH

• Each enzyme has an optimal pH in which it can function

Figure 8.18

Rat

e o

f re

actio

n

(b) Optimal pH for two enzymes

Optimal pH for pepsin (stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

10 2 3 4 5 6 7 8 9

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• Inhibitor - substance that binds to an enzyme and decreases its activity – feedback• Competitive inhibitors - compete with the

substrate for the same active site• Noncompetitive inhibitors - bind to the

enzyme in a location other than the active site

• Allosteric sites - specific binding sites acting as on/off switches

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Enzyme Inhibitors• Competitive inhibitors bind to the active site of an enzyme,

competing with the substrate

(b) Competitive inhibition

A competitiveinhibitor mimics the

substrate, competingfor the active site.

Competitiveinhibitor

A substrate canbind normally to the

active site of anenzyme.

Substrate

Active site

Enzyme

(a) Normal binding

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Enzyme Inhibitors

• Noncompetitive inhibitors bind to another part of an enzyme, changing the function

A noncompetitiveinhibitor binds to the

enzyme away fromthe active site, altering

the conformation ofthe enzyme so that its

active site no longerfunctions.

Noncompetitive inhibitor

(c) Noncompetitive inhibition

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Regulation Of Enzyme Activity Helps Control Metabolism

• Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated

• To regulate metabolic pathways, the cell switches on or off the genes that encode specific enzymes

• Allosteric regulation is the term used to describe any case in which a protein’s function at one site is affected by binding of a regulatory molecule at another site

• Enzymes change shape when regulatory molecules bind to specific sites, affecting function

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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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Allosteric Regulation of Enzymes• Allosteric regulation may either inhibit or stimulate an

enzyme’s activity

Stabilized inactiveform

Allosteric activaterstabilizes active fromAllosteric enyzme

with four subunitsActive site

(one of four)

Regulatorysite (oneof four)

Active form

Activator

Stabilized active form

Allosteric activaterstabilizes inactive form

InhibitorInactive formNon-functionalactivesite

(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.

Oscillation

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Cooperativity• Is a form of allosteric regulation that can amplify

enzyme activity

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

Substrate

Inactive form Stabilized active form

(b) Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate.

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• Activators - substances that bind to allosteric sites and keep the enzymes in their active configurations - increases enzyme activity• Cofactors - chemical components that

facilitate enzyme activity• Coenzymes - organic molecules that

function as cofactors

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Regulation of Biochemical Pathways

• Biochemical pathways must be coordinated and regulated to operate efficiently.

• Advantageous for cell to temporarily shut down biochemical pathways when their products are not needed

• Feedback Inhibition

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Feedback Inhibition

• In feedback inhibition the end product of a metabolic pathway shuts down the pathway

• When the cell produces increasing quantities of a particular product, it automatically inhibits its ability to produce more

Active siteavailable

Isoleucineused up bycell

Feedbackinhibition

Isoleucine binds to allosteric site

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

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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