Chapter 8(1)

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

PowerPoint® Lecture Presentations for

Biology Eighth Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

Chapter 8Chapter 8

An Introduction to Metabolism

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

• Metabolism is the totality of an organism’s chemical reactions

– Example of an emergent property that arises from interactions between molecules within the cell

• A metabolic pathway begins with a specific molecule and ends with a product

– Each step is catalyzed by a specific enzyme

Enzyme 1 Enzyme 2 Enzyme 3

DCBAReaction 1 Reaction 3Reaction 2

Startingmolecule

Product

• Catabolic pathways

– release energy by breaking down complex molecules into simpler compounds

– Ex: Cellular respiration (the breakdown of glucose in the presence of oxygen)

• Anabolic pathways

– consume energy to build complex molecules from simpler ones

– Ex: The synthesis of protein from amino acids


Catabolic vs Anabolic Pathways

• Energy is the capacity to cause change or do work and can be converted from one form to another

– Kinetic energy (energy of movement)

– Heat (thermal energy)

– Potential energy

– Chemical energy


Forms of Energy

Climbing up converts the kinetic energy of muscle movement to potential energy.

A diver has less potential energy in the water than on the platform.

Diving converts potential energy to kinetic energy.

A diver has more potential energy on the platform than in the water.

The Laws of Energy Transformation

• Thermodynamics is the study of energy transformations

• A closed system is isolated from its surroundings

– Ex: liquid in a thermos

• In an open system, energy and matter can be transferred between the system and its surroundings

– Ex: Organisms absorb energy and release heat


The Laws of Thermodynamics

• First Law of Thermodynamics

– Energy can be transferred and transformed, but it cannot be created or destroyed

– The energy of the universe is constant

– “principle of conservation of energy”

– Ex: plants convert sunlight to chemical energy

• Second Law of Thermodynamics

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

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


Fig. 8-3

(a) First law of thermodynamics (b) Second law of thermodynamics

Chemicalenergy

Heat CO2

H2O

+

First and Second law of Thermodynamics

Biological Order and Disorder

• Cells create ordered structures from less ordered materials

– Ex: amino acids make proteins

• Organisms also replace ordered forms of matter and energy with less ordered forms

– Ex: the break down of food molecules produces water, heat and CO2

• Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases

• Energy flows into an ecosystem in the form of light and exits as heat


The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously

• Free Energy– energy that can do work when temperature and

pressure are uniform, as in a living cell

– measure of a system’s instability

• The change in free energy (∆G) during a process is related to the change in enthalpy, or change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin (T):

Free energy change: ∆G = ∆H – T∆S


Free energy

Total energy

Temp(K)

Entropy

• Equilibrium is a state of maximum stability

• Spontaneous reactions:• ∆G < 0 (a negative ∆G)• can be harnessed to perform work when it is moving

towards equillibrium• free energy decreases and the stability of a system

increases

• G represents the difference between the free energy of the final state and the free energy of the initial stateG = Gfinal state – Ginitial state


Free-Energy Change, G

(a) Gravitational motion (b) Diffusion (c) Chemical reaction

• More free energy (higher G)• Less stable• Greater work capacity

In a spontaneous change:

• The free energy of the system decreases (∆G < 0)• The system becomes more stable• The released free energy can be harnessed to do work

• Less free energy (lower G)• More stable• Less work capacity

Relationship of free energy to stability, work capacity and spontaneous change

Unstable systems

Exergonic and Endergonic Reactions in Metabolism

• An exergonic reaction (downhill) proceeds with a net release of free energy and is spontaneous

– G is negative

– The greater the decrease in free energy, the more work can be done

• An endergonic reaction (uphill) absorbs free energy from its surroundings and is nonspontaneous

– G is positive and is the energy required to drive the reaction

• If a chemical process is exergonic/downhill then the opposite reaction must be endergonic/uphill


Fig. 8-6

Reactants

Energy

Fre

e e

ne

rgy

Products

Amount ofenergy

released(∆G < 0)

Progress of the reaction

Products

ReactantsEnergy

Fre

e e

ne

rgy

Amount ofenergy

required(∆G > 0)


Exergonic reation: energy released

Endergonic reation: energy required

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

• In life metabolism is never at equilibrium

• A catabolic pathway in a cell releases free energy in a series of reactions

• Closed and open hydroelectric systems can serve as analogies


What would happen if a cell was in equilibrium?

Fig. 8-7

(a) An isolated hydroelectric system

(b) An open hydroelectric system

∆G < 0 ∆G = 0

∆G < 0

∆G < 0

∆G < 0

∆G < 0

(c) A multistep open hydroelectric system

•Downhill flow of water turns a turbine •turbine drives a generator •Electricity turns on a light bulb•Eventually equilibrium will be reached

•Running water powers the generator•Intake and outflow of water keeps equilibrium from occurring•Electricity turns on a light bulb

•Running water powers the generator•The product becomes the reactant in the next reaction•Equilibrium will not be reached•Ex: cellular respiration

Spontaneous reaction

Similar to a catabolic pathway that releases energy

Practice Quiz

• Which one of these is the best example of a spontaneous reaction?

• Which one is more unstable?

• Which reaction is uphill? Which is downhill?

• Which reaction is endergonic? Exergonic?

• Which one will require more energy for work?

• Which one has a +G?

• Which one has a -G?

• In B, is the G going to decrease or increase?

A B

Stable UnstableUphill DownhillLess work More workLow G High GG increases G decreasesNonspontaneous SpontaneousEndergonic ExergonicAbsorbs energy Releases energy

ATP powers cellular work by coupling exergonic reactions to endergonic reactions

• A cell does three main kinds of work which all require energy:

– Chemical – the pushing of endergonic rxns that require energy

– Transport – pump substances across membranes against a gradient

– Mechanical – ex: muscle contraction, beating of cilia

• To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one

– Most energy coupling in cells is mediated by ATP


Phosphate groupsRibose

Adenine

The Structure and Hydrolysis of ATP

• ATP (adenosine triphosphate)

– is the cell’s energy shuttle

– composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups


• Hydrolysis can break the bonds between phosphate groups of ATP

• Energy is released from ATP when the terminal phosphate bond is broken (exergonic rxn)

• This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves

ATP ADP + Pi + Energy


The Structure and Hydrolysis of ATP

Higher G Lower G (more stable)

Fig. 8-9

Energy

Adenosine triphosphate (ATP)

Adenosine diphosphate (ADP)

P P

P P P

P ++

H2O

i

Inorganic phosphate

ATP + H20 ADP + Pi

G = -7.3 kcal/molExergonic

How ATP Performs Work

• Mechanical, transport, and chemical work are powered by the hydrolysis of ATP

• The energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction

• Overall, the coupled reactions are exergonic

• ATP drives endergonic reactions by phosphorylation


(b) Coupled with ATP hydrolysis, an exergonic reaction

(a) Endergonic reaction

(c) Overall free-energy change

PP

GluNH3

NH2

Glu i

GluADP+

PATP+

+

Glu

GluNH3

NH2

Glu+

Glutamicacid

GlutamineAmmonia

∆G = +3.4 kcal/mol

+Ammonia displaces the phosphate group, forming glutamine.

2

ATP phosphorylates glutamic acid,making the amino acid less stable (exergonic).

1

Overall exergonic reaction with energy

coupling

Fig. 8-11

Membrane protein

P i

ADP+

P

Solute Solute transported

P i

Cytoskeletal track

Motor protein Protein moved

ATP

ATP

(b) Mechanical work: ATP binds non-covalently to motor proteins, then is hydrolyzed

(a) Transport work: ATP phosphorylates transport proteins

The Regeneration of ATP

• ATP is a renewable resource

– ADP + Pi ATP

• The energy to phosphorylate ADP comes from catabolic reactions in the cell (those that release energy)

• The chemical potential energy temporarily stored in ATP drives most cellular work


Fig. 8-12

P iADP +

Energy fromcatabolism (exergonic,

energy-releasingprocesses)

Energy for cellularwork (endergonic,energy-consuming

processes)

ATP + H2O

Exergonic reactions drive the formation of ATP (endergonic)Endergonic reactions driven by hydrolysis of ATP (exergonic)

ATP synthesis requires energy

(endergonic)

ATP hydrolysis releases energy

(exergonic)

Energy coupling and the renewal of ATP

Enzymes speed up metabolic reactions by lowering energy barriers

• A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction

• An enzyme is a catalytic protein

– Ex: Sucrase hydrolyzes sucrose molecules


Sucrase

Sucrose

Glucose Fructose

The Activation Energy Barrier

• Every chemical reaction between molecules involves bond breaking and bond forming

• Free energy of activation

– AKA activation energy (EA)

– The initial energy needed to start a chemical reaction

– Often supplied in the form of heat from the surroundings

– Enzymes decrease EA

• Do not affect the change in free energy (∆G)

• Hasten reactions that would occur eventually


Fig. 8-14


Products

Reactants

∆G < O

Unstable transition state

Fre

e en

erg

y EA

DC

BA

D

D

C

C

B

B

A

A

Energy profile of an exergonic reaction (spontaneous)

AB + CD AC + BD

Determines the rate of the rxn

Fig. 8-15


Products

Reactants

∆G is unaffectedby enzyme

Course ofreactionwithoutenzyme

Fre

e en

erg

y

EA

withoutenzyme

EA withenzymeis lower

Course ofreactionwith enzyme

The effect of an enzyme on activation energy

Substrate Specificity of Enzymes

• The reactant that an enzyme acts on is called the enzyme’s substrate

• The enzyme binds to its substrate, forming an enzyme-substrate complex


Enzyme + Substrate(s)

Enzyme-Substratecomplex

Enzyme + Product(s)

Fig. 8-16

Substrate

Active site

Enzyme Enzyme-substratecomplex

The active site is the region on the enzyme where the substrate binds.An enzyme’s recognition of a substrate is very specific due to it AA sequence.

Induced fit between an enzyme and its substrate

Catalysis in the Enzyme’s Active Site

• substrate binds to the active site

• The active site can lower an EA barrier by

– Orienting substrates correctly

– Straining substrate bonds

– Providing a favorable microenvironment

– Covalently bonding to the substrate


Fig. 8-17

Substrates

Enzyme

Products arereleased.

Products

Substrates areconverted toproducts.

Active site can lower EA

and speed up a reaction.

Substrates held in active site by weakinteractions, such as hydrogen bonds andionic bonds.

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

Activesite is

availablefor two new

substratemolecules.

Enzyme-substratecomplex

5

3

21

6

4

Cofactors

• Cofactors are nonprotein enzyme helpers

• Cofactors may be inorganic (such as a metal in ionic form) or organic

– An organic cofactor is called a coenzyme

• Ex: vitamins


Effects of Local Conditions on Enzyme Activity

• An enzyme’s activity can be affected by

– pH

– Temperature

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

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

– Chemicals that specifically influence the enzyme• Competitive vs noncompetitive inhibitors


Fig. 8-18

Ra

te o

f re

ac

tio

n

Optimal temperature forenzyme of thermophilic

(heat-tolerant) bacteria

Optimal temperature fortypical human enzyme

(a) Optimal temperature for two enzymes

(b) Optimal pH for two enzymes

Ra

te o

f re

ac

tio

n

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

Temperature (ºC)

pH543210 6 7 8 9 10

0 20 40 80 60 100

Enzyme Inhibitors

• Competitive inhibitors bind to the active site of an enzyme, competing with the substrate

• Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective

• Ex: toxins, poisons, pesticides, and antibiotics


Fig. 8-19

(a) Normal binding (c) Noncompetitive inhibition – The shape of the enzyme is changed

(b) Competitive inhibition

Noncompetitive inhibitor

Active siteCompetitive inhibitor

Substrate

Enzyme

Types of Enzyme Inhibition

Regulation of enzyme activity helps control metabolism

• Metabolic pathways are tightly regulated

– Allosteric regulation can inhibit or stimulate an enzyme’s activity

– Feedback inhibition end product of a metabolic pathway shuts down the pathway (ie: negative feedback mechanism)

• prevents a cell from wasting chemical resources by synthesizing more product than is needed


Allosteric Regulation of Enzymes

• Enzymes are made up of several subunits or polypeptide chains which have there own active site

• Regulatory molecule binds to a protein at one site and affects the protein’s function at another site

– Activator stabilizes the active form of the enzyme

– Inhibitor stabilizes the inactive form of the enzyme

• Cooperativity

– Can amplify enzyme activity

– Binding of a substrate to one active site stabilizes favorable conformational changes at all other subunits

– One substrate molecule primes the enzyme to accept additional substrate molecules more readily


Fig. 8-20

Allosteric enyzmewith four subunits

Active site(one of four)

Regulatorysite (oneof four)

Active formActivator

Stabilized active form

Oscillation

Non-functionalactivesite

InhibitorInactive form Stabilized inactiveform

(a) Allosteric activators and inhibitors (bind to regulatory sites)

Allosteric Regulation of Enzymes

Substrate

Inactive form Stabilized activeform

(b) Cooperativity (substrate binds to active site)

Fig. 8-22

Intermediate C

Feedbackinhibition

Isoleucineused up bycell

Enzyme 1(threoninedeaminase)

End product(isoleucine)

Enzyme 5

Intermediate D

Intermediate B

Intermediate A

Enzyme 4

Enzyme 2

Enzyme 3

Initial substrate(threonine)

Threoninein active site

Active siteavailable

Active site ofenzyme 1 nolonger bindsthreonine;pathway isswitched off.

Isoleucinebinds toallostericsite

Feedback Inhibition

in isoleucine synthesis

As isoleucine accumulates,

it slows down its own synthesis by

allosterically inhibiting the

enzyme for the first step of the pathway

Practice Quiz

1. Lists the three components of ATP.

2. ________ reactions release energy while ________ reactions absorb energy

3. Cells get energy from __________ to synthesize ATP from ADP and Pi.

– Anabolic pathways, catabolic pathways, feedback inhibition, regeneration

4. Explain how energy coupling works.

5. True of False: ATP hydrolysis is exergonic and spontaneous.

6. Enzymes lower the ________ of a chemical reaction.

7. True or False: G is decreased when an enzyme is present.

8. When a protein is __________ it can become more unstable. Thus the energy from its removal can drive endergonic reactions.

9. List the three types of work that ATP does.

Chapter 8(1)

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