Chapter 8

An Introduction to Metabolism

Energy Flow in the Life of a Cell

• Energy: • the capacity to

do work

• Two type of Energy• Kinetic: energy of

movement• Potential: stored

energy• Chemical Energy:

PE available to be released in a chemical reaction

Organization of the Chemistry of Life into Metabolic Pathways

• Metabolic Pathway: Begins with a specific molecule, which is then altered in a series of defined steps resulting in a certain product.

Metabolic Pathway

Enzyme 1

A B

Reaction 1

Enzyme 2

C

Reaction 2

Enzyme 3

D

Reaction 3

ProductStarting

molecule

Types of Metabolic pathways

• Catabolic: breakdown pathways (Makes energy available) Downhill– Respiration: Breaks down glucose to produce carbon

dioxide, water and ATP

• Anabolic: Consumes energy and builds molecules (Uphill)– Photosynthesis– Synthesis of a protein

• Bioenergetics: the study of how organisms manage their energy resources.

The Laws of Thermodynamics

• The 1st Law is often called • The Law of conservation

of energy• Assumes that the total

amount of energy is constant.

• 2nd law• As energy is transferred

through the system the amount of useful energy decreases.

• No process is 100% efficient

• Regions of great [energy] are regions of great orderliness.

• Entropy

Living things Use Energy to Organize

• Living things use solar energy to synthesize complex molecules and maintain orderly structures but do this at the expense of enormous loss of usable solar energy.

• Living systers increase the entropy of their surroundings so the entropy of the universe as a whole constantly increases.

• This means that the 2nd law applies.

How Does Energy Flow in Chemical

Reactions?

• Chemical reaction, reactants, products• Exergonic (energy out)• Endergonic (energy in)• Activation energy: the valence ē ‘s of the

reactants must interact and overcome their natural (-) (-) replusion.

Coupled Reactions link Exergonic with Endergonic Reactions

• Endergonic reactions require energy.

• It gets this energy from exergonic reactions.

• Eg. Photosynthesis requires light which comes from the exergonic reaction occurring on the sun.

Examples of other coupled reactions

ATP ADP P++

ATPUnflexed Unflexed armarm ++ PPADP ++

++

Concept 8.2: The free-energy changes of a reaction tells us whether the reaction occurs

spontaneously

• Biologists want to know which reactions occur spontaneously and which require input of energy

• To do so, they need to determine energy changes that occur in chemical reactions

Free-Energy Change, G

• A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell.

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

∆G = ∆H - T∆S• Only processes with a negative ∆G are

spontaneous• Spontaneous processes can be harnessed to

perform work

Free Energy, Stability, and Equilibrium

• Free energy is 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

• A process is spontaneous and can perform work only when it is moving toward equilibrium

LE 8-5

Gravitational motion Diffusion Chemical reaction

Free Energy and Metabolism

• The concept of free energy can be applied to the chemistry of life’s processes

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)

Fre

e en

erg

y

Exergonic reaction: energy released

LE 8-6b

ReactantsEnergy

Products

Progress of the reaction

Amount ofenergy

required(G > 0)

Fre

e en

erg

y

Endergonic reaction: 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

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

• Closed and open hydroelectric systems can serve as analogies

LE 8-7a

G = 0

A closed hydroelectric system

G < 0

LE 8-7b

An open hydroelectric system

G < 0

LE 8-7c

A multistep open hydroelectric system

G < 0G < 0

G < 0

Concept 8.3: ATP powers cellular work by coupling exergonic

reactions to endergonic reactions

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

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

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 groups

Ribose

Adenine

LE 8-9

Adenosine triphosphate (ATP)

Energy

P P P

PPP i

Adenosine diphosphate (ADP)Inorganic phosphate

H2O

+ +

• 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

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

• 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

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 8-10

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

+

+ +

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

+ +

+

Electron Carriers also Transport Energy

• Excited ē’s are created during photosynthesis and cellular respiration.

• These energized ē’s are captured by electron carriers and then donated to other molecules.

• Examples: NADP+, NAD+, FAD

How Do Cells Control Their Metabolic Reactions?

1. Cells regulate chemical reations through the use of enzymes.

2. Cells couple reactions.

3. Cells synthesize energy-carrier moleucles that capture energy from exergonic reaction and transport it to endergonic reactions.

Concept 8.4: 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

At Body Temperature, Spontaneous Reactions Proceed Too Slowly to Sustain Life

• Enzymes lower the activation energy but are not used up or permanently altered.

3 Important Principles about Catalysts

• Catalysts speed up reaction

• Catalysts can speed up only those reactions that would occur spontaneously anyway, but at a much slower rate

• Catalysts are not consumed in the reactions they promote.

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

Fre

e en

erg

y

How Enzymes Lower the EA Barrier

• Enzymes catalyze reactions by lowering the EA barrier

• Enzymes do not affect the change in free-energy (∆G); instead, they hasten reactions that would occur eventually

Animation: How Enzymes Work

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

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

Catalysis in the Enzyme’s Active Site

• In an enzymatic reaction, the 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

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.

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

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 8-18

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

Cofactors

• Cofactors are nonprotein enzyme helpers

• Coenzymes are organic cofactors

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 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.

Concept 8.5: 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 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

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

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 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 activation

Stabilized active formInactive form

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)

Specific Localization of Enzymes Within the Cell

• Structures within the cell help bring order to metabolic pathways

• Some enzymes act as structural components of membranes

• Some enzymes reside in specific organelles, such as enzymes for cellular respiration being located in mitochondria

LE 8-22

Mitochondria,sites of cellular respiration

1 µm

Cells control chemical reactions by

1. Regulating synthesis of enzymes2. Producing inactive forms and activating

only when needed.