Chapter 8

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

PowerPoint Lectures for Biology, Seventh Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero

Chapter 8

An Introduction to Metabolism

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

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

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Organization of the Chemistry of Life into Metabolic Pathways

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

• Each step is catalyzed by a specific enzyme

LE 8-UN141

Enzyme 1

A BReaction 1

Enzyme 2

CReaction 2

Enzyme 3

DReaction 3

ProductStartingmolecule

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

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

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

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Forms of Energy

• Energy is the capacity to cause change

• Energy exists in various forms, some of which can perform work

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Kinetic energy is energy associated with motion– Heat (thermal energy) is kinetic energy associated

with random movement of atoms or molecules

• Potential energy is energy that matter possesses because of its location or structure

– Chemical energy is potential energy available for release in a chemical reaction

• Energy can be converted from one form to another

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.

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The First Law of Thermodynamics

• According to the first law of thermodynamics, the energy of the universe is constant

– Energy can be transferred and transformed

– Energy cannot be created or destroyed

• The first law is also called the principle of conservation of energy

LE 8-3

Chemical energy

Heat CO2

First law of thermodynamics Second law of thermodynamics

H2O

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Exergonic and Endergonic Reactions in Metabolism

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

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

LE 8-6a

Reactants

EnergyProducts

Progress of the reaction

Amount ofenergy

released(G < 0)

Free

ene

rgy

Exergonic reaction: energy released

LE 8-6b

ReactantsEnergy

Products

Progress of the reaction

Amount ofenergy

required(G > 0)

Free

ene

rgy

Endergonic reaction: energy required

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The Structure and Hydrolysis of ATP

• ATP (adenosine triphosphate) is the cell’s energy shuttle

• ATP provides energy for cellular functions

LE 8-8

Phosphate groupsRibose

Adenine

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis

• Energy is released from ATP when the terminal phosphate bond is broken

LE 8-9

Adenosine triphosphate (ATP)

Energy

P P P

PPP i

Adenosine diphosphate (ADP)Inorganic phosphate

H2O

+ +

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

• Overall, the coupled reactions are exergonic

LE 8-10Endergonic 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

+

+ +

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

LE 8-11

NH2

Glu

P i

P i

P i

P i

Glu NH3

P

P

P

ATPADP

Motor proteinMechanical 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

+ +

+

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The Regeneration of ATP

• ATP is a renewable resource that is regenerated by addition of a phosphate group to ADP

• The energy to phosphorylate ADP comes from catabolic reactions in the cell

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

LE 8-12

Pi

ADP

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

Energy from catabolism(energonic, energy-yielding processes)

ATP

+

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

• Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction

LE 8-13

SucroseC12H22O11

GlucoseC6H12O6

FructoseC6H12O6

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The Activation Energy Barrier

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

• The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (EA)

• Activation energy is often supplied in the form of heat from the surroundings

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

Free

ene

rgy

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

How Enzymes Lower the EA Barrier

• Enzymes catalyze reactions by lowering the EA barrier

LE 8-15

Course ofreactionwithoutenzyme

EA

without enzyme

G is unaffectedby enzyme

Progress of the reaction

Free

ene

rgy

EA withenzymeis lower

Course ofreactionwith enzyme

Reactants

Products

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

• The active site is the region on the enzyme where the substrate binds

• Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction

LE 8-16

Substrate

Active site

Enzyme Enzyme-substratecomplex

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Catalysis in the Enzyme’s Active Site

• In an enzymatic reaction, the substrate binds to the active site

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.

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Effects of Local Conditions on Enzyme Activity

• An enzyme’s activity can be affected by:

– General environmental factors, such as temperature and pH

– Chemicals that specifically influence the enzyme

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Effects of Temperature and pH

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

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

LE 8-18Optimal 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

Rat

e of

reac

t ion

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

pHOptimal pH for two enzymes

0

Rat

e of

r eac

t ion

1 2 3 4 5 6 7 8 9 10

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Cofactors

• Cofactors are nonprotein enzyme helpers

• Coenzymes are organic cofactors

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

LE 8-19Substrate

Active site

Enzyme

Competitiveinhibitor

Normal binding

Competitive inhibition

Noncompetitive inhibitorNoncompetitive 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.

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Allosteric Regulation of Enzymes

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

• Allosteric regulation may either inhibit or stimulate an enzyme’s activity

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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

LE 8-20a

Allosteric enzymewith four subunits

Regulatorysite (oneof four) Active form

ActivatorStabilized active form

Active site(one of four)

Allosteric activatorstabilizes active form.

Non-functionalactive site

Inactive form Inhibitor Stabilized inactive form

Allosteric inhibitorstabilizes inactive form.

Oscillation

Allosteric activators and inhibitors

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Cooperativity is a form of allosteric regulation that can amplify enzyme activity

• In cooperativity, binding by a 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 activationStabilized active formInactive form

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Feedback Inhibition

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

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

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)