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An Introduction to Metabolism Chapter 8

You should be able to:

1. Distinguish between the following pairs of

terms: catabolic and anabolic pathways;

kinetic and potential energy; open and

closed systems; exergonic and endergonic

reactions

2. In your own words, explain the second law

of thermodynamics and explain why it is

not violated by living organisms

3. Explain in general terms how cells obtain

the energy to do cellular work

4. Explain how ATP performs cellular work

5. Explain why an investment of activation

energy is necessary to initiate a

spontaneous reaction

6. Describe the mechanisms by which

enzymes lower activation energy

7. Describe how allosteric regulators may

inhibit or stimulate the activity of an

enzyme

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Overview: The Energy of Life

o The living cell is a miniature chemical factory where

thousands of reactions occur

o The cell extracts energy & applies energy to perform work

(moving/rearranging matter)

o Some organisms even convert chemical energy to light, as

in bioluminescence

o This fungus coverts chemical E stored

in certain organic molecules to light this

attracts insects which will then disperse its

spores

An organisms metabolism transforms matter and energy

(subject to the laws of thermodynamics)

o Metabolism is the totality of all an organisms chemical reactions

o Examples:

oEach dehydration reaction making monomers into a

polymer

oEach reverse condensation reaction

oEach ATP passing a phosphate group to a protein

o Metabolism is an emergent property of life that arises from

interactions between molecules within the cell

Organization of the Chemistry of

Life into Metabolic Pathways

o A metabolic pathway begins with a specific

molecule and ends with a product

o Each step is catalyzed by a specific enzyme

Enzyme 1 Enzyme 2 Enzyme 3

D C B A Reaction 1 Reaction 3 Reaction 2

Starting molecule

Product

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oStarting Substrate: Tyrosine (Amino Acid) End Product:

Epinephrine (Adrenaline)

oEach step is a reaction changing a part of the molecule

oEach step thus has its own Substrate and Product

o Catabolic pathways release energy by

breaking down complex molecules into

simpler compounds

o Cellular respiration, the breakdown of glucose

in the presence of oxygen, is an example of

catabolism

C6H12O6 + 6 O2 6 CO2 + 6 H20

o Anabolic pathways consume energy to

build complex molecules from simpler ones

o Example: synthesis of protein from amino acids

o Bioenergetics is the study of how

organisms manage their energy resources

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Forms of Energy

o Energy is the capacity to cause change

o To Alter the State of Matter, either Position

or Structure (the position of the subunits)

oRecent Example: Active Transport Changing structure of membrane proteins

o Energy exists in various forms, some of which can

perform work

o Kinetic energy is energy associated with motion

o Heat (thermal energy) is kinetic energy

associated with random movement of atoms or

molecules

o Potential energy is energy that matter possesses

because of its location or structure

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

o Energy stored in chemical bonds

o Energy can be converted from one form to another

Animation: Energy Concepts

Fig. 8-2

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.

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The Laws of Energy Transformation

o Thermodynamics is the study of energy transformations

o A closed system is isolated from its surroundings

o Ex. Light energy is trapped out

o Ex. Heat energy is trapped in

o Scientists use the word system

to denote the matter under study

Example of a closed system:

Liquid in a Thermos bottle

oIn an open system, energy and matter can be transferred between the system & its surroundings

oOrganisms are open systems

Sunlight

Ecosystem

Heat

Heat

Cycling

of

chemical

nutrients

Producers

(plants and

other

photosynthetic

organisms)

Chemical energy

Consumers

(such as

animals)

The First Law of Thermodynamics

o First Law of Thermodynamics: the energy of the universe is constant:

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

o The 1st law is also called the Principle of Conservation of Energy

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The Second Law of

Thermodynamics o During every energy transfer or transformation,

some energy is unusable, and is often lost as heat

o According to the Second Law of Thermodynamics:

o Every energy transfer or transformation

increases the entropy (disorder, S) of the

universe http://entropysite.oxy.edu/students_approach.html

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

Chemical energy

Heat

Living cells unavoidably convert organized

forms of energy to heat

o Spontaneous processes occur without energy

input

o Happen by themselves

o Just because we say spontaneous does not

mean necessarily quickly

o They can happen quickly or slowly

o For a process to occur without energy input, it

must increase the entropy of the universe

o Nonspontaneous processes require E input

o Example of spontaneous process is water flowing

down a hill spontaneously but only moves uphill

with E input such as machine pumping against

gravity

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Biological Order and Disorder 1) Cells create ordered structures from less ordered

materials

o This process requires energy

2) Organisms also replace ordered forms of matter and energy with less ordered forms (Chapters 8-9)

o This process can release energy to move or to create other ordered materials

3) Energy (usually) flows into an ecosystem in the form of light & exits in the form of heat

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

o Entropy (disorder) may decrease in an organism, but the universes total entropy increases

The Free-Energy Change of a reaction

tells us whether or not the reaction

occurs spontaneously

o Biologists want to know which reactions

occur spontaneously & which require input

of energy

o Spontaneous--Would just happen (water falling downhill)

o Energy needed--Pumping water uphill

o To do so, they need to determine energy

changes that occur in chemical reactions

Free-Energy Change, G

o A living systems free energy (G) is energy that can do work when temperature and pressure are uniform, as in a living cell

o The change in free energy (G) during a process is related to:

o the change in enthalpy (total energy (H))

o change in entropy (S)

o temperature in Kelvin (T)(K = C + 273):

(G = H TS)

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o Only processes with a negative G (-G) are spontaneous

o Spontaneous processes can be harnessed

to perform work we desire

o Free energy is a measure of a systems instability, its tendency to change to a more stable state

o Unstable/semistable things contain lots of free energy

A wobbly stool can fall

ATP

o During a spontaneous change, Free Energy

decreases & the stability of a system increases

o The wobbly stool falling

o ATP being hydrolyzed

Free Energy, Stability, and

Equilibrium

o Equilibrium is a state of maximum stability

o The wobbly stool now on the floor

o ATP without the extra P-groups (ADP, AMP)

o A process is spontaneous & can perform

work only when it is moving toward

equilibrium

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Figure 8.5

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

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

Fig. 8-5a

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

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

Free Energy and Metabolism

o The concept of free energy can be applied

to the chemistry of lifes processes

oAn Exergonic Reaction proceeds with a net

release of free energy and is spontaneous

oAn Endergonic Reaction absorbs free energy

from its surroundings and is nonspontaneous

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Fig. 8-6

Reactants

Energy

Fre

e e

nerg

y

Products

Amount of energy

released (G < 0)

Progress of the reaction

(a) Exergonic reaction: energy released

Products

Reactants

Energy

Fre

e e

nerg

y

Amount of energy

required

(G > 0)

(b) Endergonic reaction: energy required

Progress of the reaction

Ex. Water

down a hill

Ex. Water up a

hill

Equilibrium and Metabolism

o Reactions in a closed system eventually reach

equilibrium and then do no work

No place left to fall; there

is no longer a difference

between start position &

final position can no longer turn the generator

Flowing water keeps

driving the generator

because intake and

outflow of water keep the

system from reaching

equilibrium

Equilibrium and Metabolism

o Cells are not in equilibrium; they are open

systems experiencing a constant flow of

materials in and out

o A defining feature of life is that metabolism is

never at equilibrium

o Related to several of Chapter 1s properties of life

o A catabolic pathway in a cell releases free

energy in a series of reactions

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Fig. 8-7c

(c) A multistep open hydroelectric system

G < 0

G < 0

G < 0

Note: It cannot reach equilibrium or stop (or run against

concentration gradient) because each tank is used up as it is

filled

ATP powers cellular work by coupling exergonic

reactions to endergonic reactions

o A cell does 3 main kinds of work:

1. Chemical -- doing endergonic reactions

Ex. polymerization

2. Transport -- pumping against concentration gradients

3. Mechanical -- moving

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

o You have seen this before with cotransport

o Most energy coupling in cells is mediated by ATP

The Structure and Hydrolysis of ATP

o ATP (adenosine triphosphate) is the cells energy shuttle

o ATP is composed of ribose (a sugar), adenine

(a nitrogenous base), and three phosphate

groups

o ATP is also one of the nucleoside

triphosphates used to make RNA

Phosphate groups Ribose

Adenine

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o The bonds between the phosphate groups of

ATPs tail can be broken by hydrolysis

o Energy is released from ATP when the terminal

phosphate bond is broken

o This release of energy

comes from the chemical

change to a state of lower

free energy, not from the

phosphate bonds themselves

How ATP Performs Work

o The 3 types of cellular work (mechanical, transport,

and chemical) are powered by the hydrolysis of

ATP

o In the cell, the energy from the exergonic reaction

of ATP hydrolysis can be used to drive an

endergonic reaction

o Overall, the coupled reactions are exergonic

o ATP drives endergonic reactions by

phosphorylation, transferring a phosphate group

to some other molecule, such as a reactant

o The recipient molecule is now phosphorylated

Fig. 8-10

(b) Coupled with ATP hydrolysis, an exergonic reaction

Ammonia displaces the phosphate group, forming glutamine.

(a) Endergonic reaction

(c) Overall free-energy change

P

P

Glu

NH3

NH2

Glu i

Glu ADP +

P

ATP +

+

Glu

ATP phosphorylates glutamic acid, making the amino acid less stable.

Glu

NH3

NH2

Glu +

Glutamic acid

Glutamine Ammonia

G = +3.4 kcal/mol

+ 2

1

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Fig. 8-11

(b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed

Membrane protein

P i

ADP

+

P

Solute Solute transported

P i

Vesicle Cytoskeletal track

Motor protein Protein moved

(a) Transport work: ATP phosphorylates transport proteins

ATP

ATP

The Regeneration of ATP o ATP is a renewable resource that is

regenerated by addition of a phosphate group

to adenosine diphosphate (ADP)

o The energy to phosphorylate ADP comes from

catabolic reactions in the cell

o The chemical potential energy temporarily

stored in ATP drives most cellular work

P i ADP +

Energy from catabolism (exergonic, energy-releasing processes)

ATP + H2O ATP synthesis from ADP + P requires E

ATP hydrolysis to ADP + P yields E

Enzymes speed up metabolic

reactions by lowering energy barriers

o A catalyst is a chemical agent that speeds

up a reaction without being consumed by

the reaction

o An enzyme is a catalytic protein

o Hydrolysis of sucrose by the enzyme

sucrase is an example of an enzyme-

catalyzed reaction

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Fig. 8-13

Sucrose (C12H22O11)

Glucose (C6H12O6) Fructose (C6H12O6)

Sucrase

The Activation Energy Barrier

o Every chemical reaction between molecules involves (1) bond breaking and (2) bond forming

Even exergonic chemical reactions require some energy input to happen, or else they already would have happened

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

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

Fig. 8-14

Progress of the reaction

Products

Reactants

G < O

Transition state

EA

D C

B A

D

D

C

C

B

B

A

A

The reactants AB and CD must

absorb enough energy from the

surroundings to reach the unstable

transition state, where bonds can

break

After bonds have broken, new bonds

form, releasing energy to the

surroundings

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How Enzymes Lower the EA

Barrier

o Enzymes catalyze reactions by lowering the

EA barrier

o Enzymes do not affect the change in free

energy (G); instead, they speed up reactions that would occur eventually

Animation: How Enzymes Work

Fig. 8-15

Progress of the reaction

Products

Reactants

G is unaffected by enzyme

Course of reaction without enzyme

EA without enzyme EA with

enzyme is lower

Course of reaction with enzyme

Substrate Specificity of Enzymes

o The reactant that an enzyme acts on is

called the enzymes substrate

o The enzyme binds to its substrate, forming

an enzyme-substrate complex

o The active site is the region on the enzyme

where the substrate binds

o Induced fit of a substrate brings chemical

groups of the active site into positions that

enhance their ability to catalyze the reaction

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Fig. 8-16

Substrate

Active site

Enzyme Enzyme-substrate complex

(b) (a)

In this computer graphic model, the active site of

this enzyme (hexokinase) forms a groove on its

surface. Its substrate is glucose (red)

When the substrate enters the active site, it

induces a change in the shape of the protein.

This change allows more weak bonds to form,

causing the active site to enfold the substrate

and hold it in place.

Catalysis in the Enzymes Active Site

o In an enzymatic reaction, the substrate

binds to the active site of the enzyme

o The active site can lower an EA barrier by:

A. Orienting substrates correctly

B. Straining substrate bonds

C. Providing a favorable microenvironment

D. Covalently bonding to the substrate

Figure 8.15-1

Substrates

Substrates enter active site.

Enzyme-substrate complex

Substrates are held in active site by weak interactions.

1

2

Enzyme

Active site

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Figure 8.15-2

Substrates

Substrates enter active site.

Enzyme-substrate complex

Substrates are held in active site by weak interactions.

Active site can lower EA and speed up a reaction.

1

2

3

Substrates are converted to products.

4

Enzyme

Active site

Figure 8.15-3

Substrates

Substrates enter active site.

Enzyme-substrate complex

Enzyme

Products

Substrates are held in active site by weak interactions.

Active site can lower EA and speed up a reaction.

Active site is

available for two new

substrate molecules.

Products are released.

Substrates are converted to products.

1

2

3

4 5

6

Effects of Temperature and pH

Each enzyme has

an optimal

temperature &

optimal pH in

which it can

function

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Cofactors

o Cofactors are nonprotein enzyme helpers

o Cofactors may be inorganic (such as a metal

in ionic form) or organic

o An organic cofactor is called a coenzyme

o Many vitamins are coenzymes

(a) Normal binding (c) Noncompetitive inhibition (b) Competitive inhibition

Noncompetitive inhibitor

Active site Competitive inhibitor

Substrate

Enzyme

Enzyme Inhibitors o Competitive inhibitors bind to the active site of an

enzyme, competing with the substrate

o Noncompetitive inhibitors bind to another part of an

enzyme, causing the enzyme to change shape and

making the active site less effective

o Examples: toxins, poisons, pesticides, and antibiotics

Regulation of enzyme activity helps

control metabolism

o Chemical chaos would result if a cells metabolic pathways were not tightly

regulated

o A cell does this by switching on or off the

genes that encode specific enzymes

OR

o by regulating the activity of enzymes

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Allosteric Regulation of Enzymes

o Allosteric regulation may either inhibit or

stimulate an enzymes activity

o Allosteric regulation occurs when a

regulatory molecule binds to a protein at one

site and affects the proteins function at another site

Allosteric Activation and Inhibition

o Most allosterically regulated enzymes are made from polypeptide subunits (quaternary structure)

o Each enzyme has active & inactive forms

o The binding of an activator stabilizes the active form of the enzyme

o The binding of an inhibitor stabilizes the inactive form of the enzyme

o Allosteric regulators are attractive drug candidates for enzyme regulation

Fig. 8-20a

(a) Allosteric activators and inhibitors

Inhibitor Non- functional active site

Stabilized inactive form

Inactive form

Oscillation

Activator

Active form Stabilized active form

Regulatory site (one of four)

Allosteric enzyme with four subunits

Active site (one of four)

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o Cooperativity is a form of allosteric

regulation that can amplify enzyme activity

o In cooperativity, binding by a substrate to

one active site stabilizes favorable

conformational changes at all other subunits

Feedback Inhibition

o In feedback inhibition, the end product of a

metabolic pathway shuts down the pathway

o Feedback inhibition prevents a cell from

wasting chemical resources by synthesizing

more product than is needed

Fig. 8-22

Intermediate C

Feedback inhibition

Isoleucine used up by cell

Enzyme 1 (threonine deaminase)

End product

(isoleucine)

Enzyme 5

Intermediate D

Intermediate B

Intermediate A

Enzyme 4

Enzyme 2

Enzyme 3

Initial substrate (threonine)

Threonine in active site

Active site available

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

Isoleucine binds to allosteric site

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Specific Localization of Enzymes

Within the Cell

o Structures within the cell help bring order to

metabolic pathways

o Some enzymes act as structural

components of membranes

o In eukaryotic cells, some enzymes reside in

specific organelles; for example, enzymes

for cellular respiration are located in

mitochondria