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Chapter 8
An Introduction to
Metabolism
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Overview: The Energy of Life
• The living cell
– Is a miniature factory where thousands of
reactions occur
– Converts energy in many ways
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• Some organisms
– Convert energy to light, as in bioluminescence
Figure 8.1
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• Metabolism
– Is the totality of an organism’s chemical
reactions
– Arises from interactions between molecules
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Organization of the Chemistry of Life into
Metabolic Pathways
• A metabolic pathway has many steps
– That begin with a specific molecule and end
with a product
– That are each catalyzed by a specific enzyme
Enzyme 1
A
Enzyme 2
D
C
B
Reaction 1
Enzyme 3
Reaction 2
Starting
molecule
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Reaction 3
Product
• Catabolic pathways
– Break down complex molecules into simpler
compounds
– Release energy (-G)
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• Anabolic pathways
– Build complicated molecules from simpler ones
– Consume energy (+ G)
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Forms of Energy
• Energy
– Is the capacity to cause change
– Exists in various forms, of which some can
perform work
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• Kinetic energy
– Is the energy associated with motion
• Potential energy
– Is stored in the location of matter
– Includes chemical energy stored in molecular
structure
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• Energy can be converted
– From one form to another
On the platform, a diver
has more potential energy.
Climbing up converts kinetic
energy of muscle movement
Figure 8.2
to potential energy.
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Diving converts potential
energy to kinetic energy.
In the water, a diver has
less potential energy.
The First Law of Thermodynamics
• According to the first law of thermodynamics
– Energy can be transferred and transformed
– Energy cannot be created or destroyed
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• An example of energy conversion
Chemical
energy
Figure 8.3
(a) First law of thermodynamics: Energy
can be transferred or transformed but
Neither created nor destroyed. For
example, the chemical (potential) energy
in food will be converted to the kinetic
energy of the cheetah’s movement in (b).
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The Second Law of Thermodynamics
–
Every energy transfer makes universe more
disordered = increases entropy
–
When energy is transferred – some lost as heat
–
Amount of useful energy decreases when energy
is transferred
Heat
co2
+
H2O
Figure 8.3
(b) Second law of thermodynamics: Every energy transfer or transformation increases
the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s
surroundings in the form of heat and the small molecules that are the by-products
of metabolism.
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Problem:
• Living organisms are highly ordered: decrease
entropy.
• For example, Living organisms take in
disordered amino acids and order them in the
form of proteins.
• Question: Do living organisms violate the
second law?
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• NO
• Living organisms also take in ordered forms (starch)
and break them into smaller more disordered units
(glucose)
• Must consider organism and their environment
• Living organisms
– Maintain highly ordered structure at the expense of
increased entropy of surroundings
– Take in complex high energy molecules, extract
energy, release simpler low energy molecules (CO2
and H20) and heat to environment
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Energy Exchanges
• Free energy (∆G) = work that can be performed
by cell when Temp & pressure are uniform
• The change in free energy, ∆G during a
biological process
– Is related directly to the enthalpy change (∆H)
and the change in entropy (∆S)
∆G = ∆H – T∆S
∆H = change in enthalpy = heat of reaction
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Free Energy, Stability, and Equilibrium
• Organisms live at the expense of free energy
• During a spontaneous change
– ∆G is negative
• During every energy exchange (∆H) some
energy is available to do work (∆G) and some
is lost to the system (T∆S)
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• At maximum stability
– The system is at equilibrium
• More free energy (higher G)
• Less stable
• Greater work capacity
In a spontaneously 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. Objects
move spontaneously from a
higher altitude to a lower one.
Figure 8.5
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(b) Diffusion. Molecules
in a drop of dye diffuse
until they are randomly
dispersed.
(c) Chemical reaction. In a
cell, a sugar molecule is
broken down into simpler
molecules.
Exergonic and Endergonic Reactions in Metabolism
• An exergonic reaction
– Proceeds with a net release of free energy and
is spontaneous
Reactants
Free energy
Amount of
energy
released
(∆G <0)
Energy
Products
Progress of the reaction
Figure 8.6
(a) Exergonic reaction: energy released
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Exergonic Reactions
R
E
n
e
r
g
y
P
Time
•Reactants have more
energy
•More ordered to less
•Unstable to stable
•Downhill reaction
•Free energy released
•∆G is negative
•Spontaneous
•Examples:
– Cellular Respiration
– Digestion
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• An endergonic reaction
– Is one that absorbs free energy from its
surroundings and is nonspontaneous
Free energy
Products
Energy
Reactants
Progress of the reaction
Figure 8.6
(b) Endergonic reaction: energy required
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Amount of
energy
released
(∆G>0)
Endergonic Reactions
P
E
n
e
r
g R
y
Time
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•Products have more
energy than reactants
•Less ordered to more
•Stable to unstable
•Uphill reaction
•Free energy absorbed
from surroundings
•∆G is positive
•Examples:
– Photosynthesis
– Polymer synthesis
Couple Reactions
•Energy released from
exergonic reaction drives
endergonic reaction
R
E
n
e
r
g
y
P
Time
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•Exergonic reaction ∆G =
maximum work that can be
done
•Endergonic reaction ∆G =
minimum work needed to
drive the reaction
• 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
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ATP
• Adenosine triphosphate
• Has unstable phosphate bonds
Adenine
Unstable high energy bonds
Phosphate groups
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Ribose (5-C sugar)
The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate)
– Is the cell’s energy shuttle
– Provides energy for cellular functions
Adenine
N
O
O
-O
O
-
O
-
O
O
C
C
N
HC
O
O
O
NH2
-
Phosphate groups
Figure 8.8
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N
CH2
O
H
N
H
H
H
OH
CH
C
OH
Ribose
• Energy is released from ATP
– When the terminal phosphate bond is broken
P
P
P
Adenosine triphosphate (ATP)
H2O
P
i
+
Figure 8.9 Inorganic phosphate
P
P
Adenosine diphosphate (ADP)
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Energy
Production
Exergonic
Energy from
catabolism
ATP
Endergonic Energy
for cellular work
∆G= -7.3 kcal/mol
∆G= +7.3 kcal/mol
ADP + Pi
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How Does ATP Work
•Mechanical:
•Chemical:
– Beating cilia
– Endergonic reactions
– Muscular contraction
– Polymerization
– Movement
•Transport:
– Active transport
– Pumps (H+ and
Na+/K+)
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• Energy coupling
– Is a key feature in the way cells manage their
energy resources to do this work
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• ATP hydrolysis
–
CanEndergonic
be coupled
to other reactions
reaction: ∆G is positive, reaction
is not spontaneous
NH2
Glu
+
Glutamic
acid
NH3
Glu
Ammonia
Glutamine
∆G = +3.4 kcal/mol
Exergonic reaction: ∆ G is negative, reaction
is spontaneous
ATP
+
H2O
ADP +
Coupled reactions: Overall ∆G is negative;
together, reactions are spontaneous
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P
∆G = + 7.3 kcal/mol
∆G = –3.9 kcal/mol
How ATP Performs Work
• ATP drives endergonic reactions
– By phosphorylation, transferring a phosphate
to other molecules
P
ATP
GLU
GLU
∆G= -7.3 kcal/mol
P
NH2
NH3
GLU
GLU
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∆G = +3.4 kcal/mol
∆G = –3.9 kcal/mol
Overall Rxn is
exergonic
• The three types of cellular work
– Are powered by the hydrolysis of ATP
P
i
P
Motor protein
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
ATP
P
P
Solute
P
i
Solute transported
(b) Transport work: ATP phosphorylates transport proteins
P
Glu + NH3
Reactants: Glutamic acid
and ammonia
Figure 8.11
NH2
Glu
+
P
i
Product (glutamine)
made
(c) Chemical work: ATP phosphorylates key reactants
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i
The Regeneration of ATP
• Catabolic pathways
– Drive the regeneration of ATP from ADP and
phosphate
ATP hydrolysis to
ADP + P i yields energy
ATP synthesis from
ADP + P i requires energy
ATP
Energy from catabolism
(exergonic, energy yielding
processes)
Figure 8.12
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Energy for cellular work
(endergonic, energyconsuming processes)
ADP + P
i
• 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
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• An enzyme
– Is a catalytic protein
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The Activation Barrier
• Every chemical reaction between molecules
– Involves both bond breaking and bond forming
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• The hydrolysis
– Is an example of a chemical reaction
CH2OH
CH2OH
O
O
H H
H
H
OH
H HO
O
+
CH2OH
H
Sucrase
H2O
OH H
OH
CH2OH
O H
H
H
OH H
OH
HO
H
OH
CH2OH
O
HO
H HO
H
CH2OH
OH H
Sucrose
Glucose
Fructose
C12H22O11
C6H12O6
C6H12O6
Figure 8.13
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• The activation energy, EA
– Is the initial amount of energy needed to start a
chemical reaction
– Is often supplied in the form of heat from the
surroundings in a system
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• The energy profile for an exergonic reaction
A
B
C
D
Free energy
Transition state
A
B
C
D
EA
Reactants
A
B
C
D
∆G < O
Products
Progress of the reaction
Figure 8.14
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How Enzymes Lower the EA Barrier
• An enzyme catalyzes reactions
– By lowering the EA barrier
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• The effect of enzymes on reaction rate
Course of
reaction
without
enzyme
EA
without
enzyme
Free energy
EA with
enzyme
is lower
Reactants
∆G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
Figure 8.15
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Substrate Specificity of Enzymes
• The substrate
– Is the reactant an enzyme acts on
• The enzyme
– Binds to its substrate, forming an enzymesubstrate complex
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• The active site
– Is the region on the enzyme where the
substrate binds
Substate
Active site
Enzyme
Figure 8.16
(a)
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• Induced fit of a substrate
– Brings chemical groups of the active site into
positions that enhance their ability to catalyze
the chemical reaction
Enzyme- substrate
complex
Figure 8.16
(b)
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Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction
– The substrate binds to the active site
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• The catalytic cycle of an enzyme
1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates
Enzyme-substrate
complex
6 Active site
Is available for
two new substrate
Mole.
Enzyme
5 Products are
Released.
Figure 8.17
Products
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2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
3 Active site (and R groups of
its 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.
4 Substrates are
Converted into
Products.
• The active site can lower an EA barrier by
– Orienting substrates correctly
– Straining substrate bonds
– Providing a favorable microenvironment
– Covalently bonding to the substrate
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Effects of Local Conditions on Enzyme Activity
• The activity of an enzyme
– Is affected by general environmental factors
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Effects of Temperature and pH
• Each enzyme
– Has an optimal temperature in which it can
function
Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
Rate of reaction
(heat-tolerant)
bacteria
0
20
40
Temperature (Cº)
(a) Optimal temperature for two enzymes
Figure 8.18
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80
100
– Has an optimal pH in which it can function
Optimal pH for pepsin
(stomach enzyme)
Rate of reaction
Optimal pH
for trypsin
(intestinal
enzyme)
3
4
0
2
1
(b) Optimal pH for two enzymes
Figure 8.18
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5
6
7
8
9
Cofactors
• Cofactors
– Are nonprotein enzyme helpers
• Coenzymes
– Are organic cofactors
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Enzyme Inhibitors
• Competitive inhibitors
– Bind to the active site of an enzyme, competing with
the substrate
A substrate can
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
(a) Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
Figure 8.19
(b) Competitive inhibition
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Competitive
inhibitor
• Noncompetitive inhibitors
– Bind to another part of an enzyme, changing
the function
A noncompetitive
inhibitor binds to the
enzyme away from
the active site, altering
the conformation of
the enzyme so that its
active site no longer
functions.
Noncompetitive inhibitor
Figure 8.19
(c) Noncompetitive inhibition
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• Concept 8.5: Regulation of enzyme activity
helps control metabolism
• A cell’s metabolic pathways
– Must be tightly regulated
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Allosteric Regulation of 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
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Allosteric Activation and Inhibition
• Many enzymes are allosterically regulated
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– They change shape when regulatory molecules bind
to specific sites, affecting function
Allosteric enyzme
with four subunits
Regulatory
site (one
of four)
Active site
(one of four)
Activator
Active form
Stabilized active form
Oscillation
Allosteric activater
stabilizes active form
NonInactive form Inhibitor
functional
active
site
Figure 8.20
Allosteric activater
stabilizes active from
Stabilized inactive
form
(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors
dissociate when at low concentrations. The enzyme can then oscillate again.
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• Cooperativity
– Is a form of allosteric regulation that can
amplify enzyme activity
Binding of one substrate molecule to
active site of one subunit locks
all subunits in active conformation.
Substrate
Inactive form
Figure 8.20
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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Feedback Inhibition
• In feedback inhibition
– The end product of a metabolic pathway shuts
down the pathway
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• Feedback inhibition
Active site
available
Initial substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition
Active site of
enzyme 1 no
longer binds
threonine;
pathway is
switched off
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
Figure 8.21
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End product
(isoleucine)
Specific Localization of Enzymes Within the Cell
• Within the cell, enzymes may be
– Grouped into complexes
– Incorporated into membranes
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– Contained inside organelles
Mitochondria,
sites of cellular respiraion
Figure 8.22
1 µm
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