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Chapter 8 Key Concepts
• Introduction to Metabolism:
– Examples of endergonic and exergonic
reactions
– Role of ATP in energy coupling
– Enzyme lowers activation energy.
– Catalytic cycle of an enzyme
– Factors that affect enzyme activity
Concept 8.1: An organism’s metabolism
transforms matter and energy, subject to the
laws of thermodynamics
• Metabolism
– Catabolism:
“energy releasing”
– Anabolism:
“energy
consuming”
© 2011 Pearson Education, Inc.
Figure 8.3a
Chemical
energy
(a) First law of thermodynamics
= conservation of energy
Figure 8.3b
Heat
(b) Second law of thermodynamics =
law of entropy
Living Organisms and Order
How do living organisms create macromolecules,
organelles, cells, tissues, and complex higher-order
structures?
a) The laws of thermodynamics do not apply to living
organisms.
b) Living organisms create order by using energy
from the sun.
c) Living organisms create order locally, but the
energy transformations generate waste heat that
increases the entropy of the universe.
FREE-ENERGY, ∆G
•Energy that can do work
•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)
∆G = ∆H – T∆S
•Only processes with a negative ∆G are
spontaneous
•Spontaneous processes can be harnessed to
perform work
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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
Exergonic and Endergonic Reactions in
Metabolism
• exergonic reaction: net release of free energy
and is spontaneous
• endergonic reaction: absorbs free energy from
its surroundings and is nonspontaneous
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(a) Exergonic reaction: energy released, spontaneous
Reactants
Free energy
Amount of
energy
released
(G  0)
Energy
Products
Progress of the reaction
(b) Endergonic reaction: energy required, nonspontaneous
Products
Free energy
Figure 8.6
Amount of
energy
required
(G  0)
Energy
Reactants
Progress of the reaction
Life and Chemical Equilibrium
Are most chemical reactions at equilibrium in
living cells?
a)
b)
c)
d)
yes
no
only the exergonic reactions
all reactions except those powered by ATP
hydrolysis
Rate of a Chemical Reaction
The oxidation of glucose to CO2 and H2O is highly
exergonic: G = –636 kcal/mole. Why doesn’t
glucose spontaneously combust?
a) The glucose molecules lack the activation energy at
room temperature.
b) There is too much CO2 in the air.
c) CO2 has higher energy than glucose.
d) The formation of six CO2 molecules from one glucose
molecule decreases entropy.
e) The water molecules quench the reaction.
Figure 8.7c
G  0
G  0
G  0
(c) A multistep open hydroelectric system
Figure 8.8
Adenine
Phosphate groups
Ribose
(a) The structure of ATP
Adenosine triphosphate (ATP)
Energy
Inorganic
phosphate
Adenosine diphosphate (ADP)
(b) The hydrolysis of ATP
Figure 8.9
(a) Glutamic acid
conversion
to glutamine
NH3
Glutamic
acid
(b) Conversion
reaction
coupled
with ATP
hydrolysis
NH2
Glu
Glu
GGlu = +3.4 kcal/mol
Glutamine
Ammonia
NH3
P
1
Glu
ATP
Glu
2
ADP
Glu
Phosphorylated
intermediate
Glutamic
acid
NH2
Glutamine
GGlu = +3.4 kcal/mol
(c) Free-energy
change for
coupled
reaction
NH3
Glu
GGlu = +3.4 kcal/mol
+ GATP = 7.3 kcal/mol
Net G = 3.9 kcal/mol
ATP
NH2
Glu
GATP = 7.3 kcal/mol
ADP
Pi
ADP
Pi
Figure 8.10
Transport protein
Solute
ATP
ADP
P
Pi
Pi
Solute transported
(a) Transport work: ATP phosphorylates transport proteins.
Cytoskeletal track
Vesicle
ATP
ADP
ATP
Motor protein
Protein and
vesicle moved
(b) Mechanical work: ATP binds noncovalently to motor
proteins and then is hydrolyzed.
Pi
Figure 8.11
ATP
Energy from
catabolism (exergonic,
energy-releasing
processes)
ADP
H2O
Pi
Energy for cellular
work (endergonic,
energy-consuming
processes)
Figure 8.UN02
Sucrase
Sucrose
(C12H22O11)
Glucose
(C6H12O6)
Fructose
(C6H12O6)
Figure 8.12
A
B
C
D
Free energy
Transition state
A
B
C
D
EA
Reactants
A
B
G  O
C
D
Products
Progress of the reaction
Figure 8.13
Free energy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
Substrate Specificity of Enzymes
• substrate
• enzyme-substrate complex
• active site
• Induced fit
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Figure 8.14
Substrate
Active site
Enzyme
(a)
Enzyme-substrate
complex
(b)
Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction, the substrate binds to
the active site of the enzyme
• The active site can lower an EA barrier by
–
–
–
–
Orienting substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Covalently bonding to the substrate
© 2011 Pearson Education, Inc.
Figure 8.15-1
1 Substrates enter active site.
2 Substrates are held
in active site by weak
interactions.
Substrates
Enzyme-substrate
complex
Active
site
Enzyme
Figure 8.15-2
1 Substrates enter active site.
2 Substrates are held
in active site by weak
interactions.
Substrates
Enzyme-substrate
complex
3 Active site can
lower EA and speed
up a reaction.
Active
site
Enzyme
4 Substrates are
converted to
products.
Figure 8.15-3
1 Substrates enter active site.
2 Substrates are held
in active site by weak
interactions.
Substrates
Enzyme-substrate
complex
3 Active site can
lower EA and speed
up a reaction.
6 Active
site is
available
for two new
substrate
molecules.
Enzyme
5 Products are
released.
4 Substrates are
converted to
products.
Products
Figure 8.16
Rate of reaction
Optimal temperature for
Optimal temperature for
typical human enzyme (37°C) enzyme of thermophilic
(heat-tolerant)
bacteria (77°C)
60
80
Temperature (°C)
(a) Optimal temperature for two enzymes
0
20
40
Rate of reaction
Optimal pH for pepsin
(stomach
enzyme)
0
5
pH
(b) Optimal pH for two enzymes
1
2
3
4
120
100
Optimal pH for trypsin
(intestinal
enzyme)
6
7
8
9
10
Cofactors
• Cofactors
• organic cofactor = coenzyme
– vitamins
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Figure 8.17
Enzyme Inhibitors
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive
inhibition
Substrate
Active
site
Competitive
inhibitor
Enzyme
Competitive inhibitors
Noncompetitive inhibitors
Noncompetitive
inhibitor
Examples of inhibitors include toxins,
poisons, pesticides, and antibiotics
Enzyme Inhibitors
Vioxx and other prescription nonsteroidal antiinflammatory drugs (NSAIDs) are potent inhibitors of
the cycloxygenase-2 (COX-2) enzyme. High substrate
concentrations reduce the efficacy of inhibition by
these drugs. These drugs are
a)
b)
c)
d)
e)
competitive inhibitors.
noncompetitive inhibitors.
allosteric regulators.
prosthetic groups.
feedback inhibitors.
The Evolution of Enzymes
• Enzymes = proteins encoded by genes
• Changes (mutations) in genes lead to changes
in amino acid composition of an enzyme
• Altered amino acids in enzymes may alter their
substrate specificity
• Under new environmental conditions a novel
form of an enzyme might be favored
© 2011 Pearson Education, Inc.
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
© 2011 Pearson Education, Inc.
Figure 8.19
(b) Cooperativity: another type of allosteric activation
(a) Allosteric activators and inhibitors
Allosteric enzyme
with four subunits
Active site
(one of four)
Regulatory
site (one
of four)
Substrate
Activator
Inactive form
Stabilized active form
Active form
Oscillation
Nonfunctional
active site
Inactive form
Inhibitor
Stabilized inactive
form
Stabilized active
form
• Cooperativity is a form of allosteric regulation
that can amplify enzyme activity
• One substrate molecule primes an enzyme to
act on additional substrate molecules more
readily
• Cooperativity is allosteric because binding by a
substrate to one active site affects catalysis in
a different active site
© 2011 Pearson Education, Inc.
Identification of Allosteric Regulators
• Allosteric regulators are attractive drug
candidates for enzyme regulation because of
their specificity
• Inhibition of proteolytic enzymes called
caspases may help management of
inappropriate inflammatory responses
© 2011 Pearson Education, Inc.
Figure 8.20
EXPERIMENT
Caspase 1
Active
site
Substrate
SH
Active form can
bind substrate
SH
Known active form
SH
Allosteric
binding site
Known inactive form
Allosteric
inhibitor
Hypothesis: allosteric
inhibitor locks enzyme
in inactive form
RESULTS
Caspase 1
Inhibitor
Active form
Allosterically
inhibited form
Inactive 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
© 2011 Pearson Education, Inc.
Figure 8.21
Active site
available
Isoleucine
used up by
cell
Active site of
Feedback
enzyme 1 is
inhibition
no longer able
to catalyze the
conversion
of threonine to
intermediate A;
pathway is
switched off. Isoleucine
binds to
allosteric
site.
Initial
substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Intermediate A
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)