Chapter 6 An Introduction to Metabolism
 6.1 An organism’s metabolism transforms matter and energy
 6.2 The free-energy change of a reaction tells us whether or not the
reaction occurs spontaneously
 6.3 ATP powers cellular work by coupling exergonic reactions to
endergonic reactions
The Energy of Life
The living cell is a miniature chemical factory where thousands of
reactions occur
- The cell extracts energy and applies energy to perform work
- converts energy in many ways. Some cells convert energy to light,
bioluminescence
 6.4 Enzymes speed up metabolic reactions by lowering energy
barriers
 6.5 Regulation of enzyme activity helps control metabolism
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Bioluminescence:
Organisms converting energy to light
Metabolism: All chemical reactions in a cell
 Metabolic pathway has series of chemical reaction
- begin with a specific molecule and end with a
product
-
catalyzed by a specific enzyme
Enzyme 1
Enzyme 1
Reaction
Enzyme
11
Starting
molecule
A
Enzyme 2
B
Enzyme 2
Reaction
Enzyme
22
Enzyme 3
C
Enzyme 3
Reaction
Enzyme
33
D
Product
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Metabolic Pathways
 Two types of metabolic pathways
1. Catabolic pathways
 Break down complex molecules into simpler
compounds
 Release energy
2. Anabolic pathways
 Synthesis of complex molecules from simpler ones
 require energy
 The synthesis of protein from amino acids is an example of
anabolism
 Photosynthesis, synthesis of glucose from carbon dioxide, water
and sunlight
Cellular respiration, the breakdown of glucose in
the presence of oxygen, is an example of a pathway
of catabolism
1
What is Kinetic Energy?
 Two major factors involved in metabolism
 Energy
Kinetic energy is energy associated with motion
 Enzymes
Examples
Energy is the capacity to cause change
- Energy exists in various forms, some of which can perform work
- Thermal energy is kinetic energy associated
with random movement of atoms or molecules
 Heat is thermal energy in transfer from one
object to another
What are examples of work that a cell has to do?
-
-Synthesizing DNA, RNA, proteins
-Moving vesicles in a cell
Light (movement of photons)- can be
harnessed to perform work
- Electricity (movement of electrons),
-Pumping substances across membranes
- a person running or a muscle contracting
- Muscles contracting
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What is Potential Energy?
Potential energy is stored energy
A diver has more potential
energy on the platform.
Diving converts
potential energy to
kinetic energy.
Depends on either:
- Structure of the molecule/object
- Position of the molecule/object
Examples
 Chemical energy in food
 Energy from a proton gradient
Chemical Energy of
Food
Energy from a
Gradient
Climbing up converts the kinetic
energy of muscle movement
to potential energy.
A diver has less
potential energy in
the water.
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The Laws of Energy Transformation
 Thermodynamics is the study of energy transformations
 According to the first law of thermodynamics, the energy
of the universe is constant
 Energy can be transferred and transformed,
but it cannot be created or destroyed
The Second Law of Thermodynamics
Second law of thermodynamics
 Every energy transfer or transformation increases the entropy
of the universe
 Entropy is a measure of disorder, or randomness
 During every energy transfer or transformation, some energy is
lost as heat, a disorganized form of energy
Heat
CO2
The brown bear converts
chemical energy from food (fish)
into kinetic energy to carry out
biological processes ( or running)
H2 O
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2
Biological Order and Disorder
 Cells create ordered structures from less ordered materials
 Organisms also replace ordered forms of matter and energy with
less ordered forms
 Energy flows into an ecosystem in the form of light and exits in the
form of heat
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 The evolution of more complex organisms does not violate the
second law of thermodynamics
 Entropy (disorder) may decrease in a system, but the universe’s
total entropy increases
 Organisms are islands of low entropy in an increasingly random
universe
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The free-energy change of a reaction tells us whether
or not the reaction occurs spontaneously
 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 chemical reaction is the
difference between the free energy of the final state and the free
energy of the initial state
∆G = Gfinal state – Ginitial state
 Only processes with a negative ∆G are spontaneous
 Spontaneous processes can be harnessed to perform work
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Free Energy and Metabolism
 A living system’s free energy is energy that can do work
under cellular conditions
The relationship of free energy to stability, work capacity, and
spontaneous change
• 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
(c) Chemical
reaction
(b) Diffusion
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Exergonic reaction: energy released, spontaneous
• Spontaneous reactions
• Reactants have more energy than products
Based on energy, there are two types of chemical reactions
Reactants
1. Exergonic reaction: reactions that release energy
e.g. Breakdown of glucose in the presence of oxygen
Amount of
energy
released
(G  0)
Free energy
Glucose + Oxygen → Carbon dioxide + water + Energy (ATP or Heat)
Energy
Products
Progress of the reaction
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3
Exergonic reactions
Endergonic reaction: energy required,
• Nonspontaneous
• Products have more energy than reactants
Exergonic reactions: Reactants have more free energy than the
products
Associated with Catabolic reactions
Products
∆G is negative
-
Spontaneous reactions
-
Released energy can be used to make ATP
ATP
Free energy
-
Amount of
energy
required
(G  0)
Energy
Reactants
Progress of the reaction
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Endergonic reactions
2. Endergonic reaction: Reactions that requires energy
Endergonic reactions: Reactants have less free energy than the
products
-
e.g. Photosynthesis – synthesis of glucose using light
energy
Associated with Anabolic reactions
-
∆G is positive
-
Non-Spontaneous reactions
-
Requires INPUT of ATP
Carbon dioxide + Water + Sunlight → Glucose + Oxygen
ATP
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Which of the following reactions is most likely to be exergonic?
Which of the following is true about endergonic reactions?
A. the synthesis of a triglyceride from glycerol and fatty acids
B. the replication of DNA from free nucleotides
A. The products of endergonic reactions have more free energy than
the reactants.
C. the formation of cellulose from individual glucose molecules
B. Energy is released from the reactants.
D. the digestion of protein from food into amino acids
C. There is a positive ΔG.
4
Think/pair/share
Energy Coupling and ATP: ATP powers cellular work
 A cell does three main kinds of work which requires
energy
 Mechanical – movement
 Transport – Active transport
 Chemical – metabolism
 To do work, cells manage energy resources by energy
coupling, the use of an exergonic process to drive an
endergonic one
1. This pathway is a(n):
A.
CATABOLIC pathway
B.
ANABOLIC pathway
 Most energy coupling in cells is mediated by ATP
2.
What other words could you use to describe this pathway?
3.
Can you give examples of 1) Catabolic reactions & 2) Anabolic Reactions
that are happening in your body right now
Energy Coupling and ATP
Structure of ATP
To do work, cells manage energy resources by energy coupling, the
use of an exergonic process to drive an endergonic one
- Most energy coupling in cells is mediated by ATP
- ATP (adenosine triphosphate) is composed of ribose (a
sugar), adenine (a nitrogenous base), and three phosphate
groups
ATP is the energy currency of a cell
ATP (adenosine triphosphate) is the cell’s energy shuttle
ATP is composed of ribose (a sugar), adenine
(a nitrogenous base), and three phosphate groups
- In addition to its role in energy coupling, ATP is also used to
make RNA
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Hydrolysis of ATP releases a lot of energy
P
P
Coupling exergonic reactions to endergonic reactions
P
P
ATP
Glu
Glu
ADP
Phosphorylated
intermediate
Glutamic acid
Adenosine triphosphate (ATP)
NH3
H 2O
P
Glu
Pi
P
P
Energy
Phosphorylated
intermediate
ADP
NH2
ADP
Glu
Pi
Glutamine
(b) Conversion reaction coupled with ATP hydrolysis
GGlu  3.4 kcal/mol
Inorganic
phosphate
GATP  7.3 kcal/mol
Adenosine diphosphate (ADP)
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Net G  3.9 kcal/mol
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How ATP drives transport and mechanical work
Transport protein
Solute
ATP
How does hydrolysis of ATP Performs Cellular Work?
ADP
P
Pi
Pi
- The recipient molecule is now called a phosphorylated
intermediate
Solute transported
(a) Transport work: ATP phosphorylates transport proteins.
Vesicle
ATP
• Transport and mechanical work in the cell are powered by ATP
hydrolysis
Cytoskeletal track
ADP
ATP
Motor protein
 ATP drives endergonic reactions by phosphorylation,
transferring a phosphate group to some other molecule, such as a
reactant, transport protein or motor protein
Pi
• ATP hydrolysis leads to a change in a protein’s shape and often
its ability to bind to another molecule
Protein and vesicle moved
(b) Mechanical work: ATP binds noncovalently to motor proteins
and then is hydrolyzed.
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How the Hydrolysis of ATP Performs work
Figure 8.12
The ATP Cycle
 ATP powers cellular work by coupling exergonic
reactions to endergonic reactions
Hydrolysis
ATP
 ATP transfers energy from an exergonic
reaction to an endergonic reaction
 In the cell, the energy from the exergonic reaction
of ATP hydrolysis can be used to drive an
endergonic reaction
 The three types of cellular work (mechanical,
transport, and chemical) are powered by the
hydrolysis of ATP
The Regeneration of ATP
Energy from
catabolism
(exergonic, energyreleasing processes)
ADP
H2O
Pi
Phosphorylation
Cellular Respiration
Energy for cellular
work (endergonic
energy-consuming
processes)
Cellular work:
Active transport
Movement
Anabolic pathway
Figure 8.UN02
Enzymes
ATP is a renewable resource that is regenerated by addition of a
phosphate group to ADP
 Catalyst that speed up chemical reactions without undergoing any
change
- The energy to phosphorylate ADP comes from catabolic
reactions in the cell
 Is a catalytic protein
Sucrase
- The ATP cycle is a revolving door through which energy passes
during its transfer from catabolic to anabolic pathways
Sucrose
(C12H22O11)
Glucose
(C6H12O6)
Fructose
(C6H12O6)
 Hydrolysis of sucrose by the enzyme sucrase is an example of
enzyme catalyzed reaction
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6
Activation Energy Barrier (EA)
The effect of an enzyme on activation energy
A
B
C
D
Course of
reaction
without
enzyme
A
B
C
D
EA
Reactants
A
B
C
D
G  0
Free energy
Free energy
Transition state
EA
without
enzyme
EA with
enzyme
is lower
Reactants
G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Products
Progress of the reaction
Progress of the reaction
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How Enzymes Speed Up Reactions
Activation Energy
 Chemical reactions involve making and breaking of the
bonds
Organisms use Enzymes to speed up reactions
Enzymes
 The initial energy needed to start a chemical reaction is
called the free energy of activation, or activation
energy (EA)
- Speed up a reaction by lowering the activation energy (EA)
barrier (lowering the activation energy requirement)
 Activation energy is often supplied in the form of heat
from the surroundings
- Do not affect the change in free energy (∆G);
- Remain unchanged at the end of the reaction
- Instead, they hasten reactions that would occur eventually
- Usually are proteins, although some RNA molecules can
function as enzymes
- How do Enzymes Work?
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Substrate Specificity of Enzymes
Enzymes are very specific for the reactions they catalyze
- 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
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Enzyme specificity results from the complementary fit between
the shape of the enzyme’s active site and the shape of the substrate
- Enzymes change shape due to chemical interactions with the
substrate
- This induced fit of the enzyme to the substrate brings chemical
groups of the active site together
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7
Figure 6.14
 The active site is the region on the enzyme where the
substrate binds
Enzyme Action
Substrates enter
active site.
Substrates are
held in active site by
weak interactions.
 Induced fit brings chemical groups of the active site
into position to catalyze the reaction
Substrate
Substrates
Enzyme-substrate
complex
Active site
is available
for new
substrates.
Active site
Enzyme
Enzyme
(a)
Products are
released.
Enzyme-substrate
complex
(b)
Products
Substrates are
converted to
products.
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Catalysis in the Enzyme’s Active Site
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
The rate of enzyme catalysis can usually be sped up by increasing
the substrate concentration in a solution
- When all enzyme molecules in a solution are bonded with
substrate, the enzyme is saturated
- At enzyme saturation, reaction speed can only be increased by
adding more enzyme
- Covalently bonding to the substrate
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You notice that a chemical reaction is happening at a slow rate.
You want to speed up the reaction. What do you do?
How might an enzyme inhibitor slow down the action of an
enzyme without binding to the active site?
A. add more products
A. by binding the substrate
B. change the ΔG for the reaction
B. by binding the enzyme and changing its shape
C. add an enzyme that catalyzes the reaction
C. by lowering the activation energy
D. increase the activation energy
D. by changing the shape of the substrate
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Effects of Local Conditions on Enzyme Activity
An enzyme’s activity can be affected by
Optimal temperature for
Optimal temperature for
typical human enzyme (37C) enzyme of thermophilic
(heat-loving)
bacteria (75C)
- General environmental factors, such as temperature and pH
 Each enzyme has an optimal temperature and pH at which
its reaction rate is the greatest
Rate of reaction
- Chemicals that specifically influence the enzyme
0
20
40
60
80
Temperature (C)
(a) Optimal temperature for two enzymes
100
120
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Effects of Temperature and pH
Optimal pH for trypsin
(intestinal
enzyme)
Rate of reaction
Optimal pH for pepsin
(stomach
enzyme)
 Each enzyme has an optimal temperature in which it can
function
 Each enzyme has an optimal pH in which it can function.
Most enzymes function at neutral pH
 Optimal conditions favor the most active shape for the
enzyme molecule
5
pH
(b) Optimal pH for two enzymes
0
1
2
3
4
6
7
8
9
10
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Cofactors and Coenzymes
Enzyme Inhibitors
 Cofactors
 Are nonprotein enzyme helpers
(a) Normal binding
(b) Competitive inhibition
 Ex. Zinc, Iron, Copper etc
 Coenzymes
Substrate
Active site
 Are organic cofactors
 Ex. Vitamins
(c) Noncompetitive
inhibition
Competitive
inhibitor
Enzyme
Both cofactors and coenzymes are required for enzyme activity
Noncompetitive
inhibitor
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9
Enzyme Inhibitors
Enzyme Inhibitors
Competitive inhibitors
Beneficial drugs that act as enzyme inhibitors include:
- bind to the active site of an enzyme
- Ibuprofen, inhibiting the production of prostaglandins,
- compete with the substrate for binding
- many antibiotics
Noncompetitive inhibitors
- do not bind to the active site of the enzyme
Harmful inhibitors of human enzymes include:
- However, they bind to another part of an enzyme, causing the
enzyme to change shape and making the active site less
effective
- Examples of inhibitors include toxins, poisons, pesticides,
and antibiotics
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- Toxins, poisons, & pesticides
 Arsenic, mercury, and lead bind act as permanent noncompetitive inhibitors of various enzymes
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Biology and Society
The Evolution of Enzymes
Many insecticides operate as permanent
enzyme inhibitors. Organo-phosphate
insecticides interfere with nerve
transmission, affecting not only insects
but also humans and other vertebrates.
Use of such insecticides is carefully
regulated and requires caution.
Mutations in in enzymes may alter their activity or substrate
specificity
- Under new environmental conditions a novel form of an enzyme
might be favored
Is an unblemished and low-cost food
supply worth the risk of the pesticide use?
Would you be willing to pay a
little more for slightly blemished but
otherwise healthy food products—
especially if pesticides were not used?
Strongly
Disagree
A
B
C
D
E
Strongly
Agree
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Regulation of enzyme activity helps control
metabolism
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Allosteric Enzymes
Chemical chaos would result if a cell’s metabolic pathways were not
tightly regulated
 Allosteric enzymes:
A cell does this by
- Have 2 or more active sites
1. Switching on or off the genes that encode specific enzymes or
- Made of 2 or more polypeptides
- Can be activated or inhibited
2. Regulating the activity of enzymes
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10
(Allosteric activators and inhibitors
Allosteric Regulation of Enzymes
Allosteric enzyme Active site
with four subunits (one of four)
Allosteric regulation may either inhibit or stimulate an enzyme’s
activity
Regulatory
site (one
Activator
of four)
Active form
Stabilized
active form
- Allosteric regulation occurs when a regulatory molecule binds to
a protein at one site and affects the protein’s function at another
site
- Reversible
Oscillation
Nonfunctional
active site
Inhibitor
Inactive form
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Stabilized
inactive form
Allosteric Activation and Inhibition
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Cooperativity: another type of allosteric activation
Substrate
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
- The activators/inhibitors bind to sites on the enzyme other than
the active site
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
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Figure 6.20
Feedback Inhibition
In feedback inhibition the
end product of a metabolic
pathway shuts down the
pathway when the end
product allosterically inhibits
the enzyme that acts early in
the pathway
Feedback inhibition prevents
a cell from wasting chemical
resources by synthesizing
more product than is needed
Mitochondrion
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Enzymes for another
stage of cellular
respiration are
embedded in the
inner membrane.
1 m
The matrix contains
enzymes in solution that
are involved in one stage
of cellular respiration.
11
Think/Pair/Share
Organization of Enzymes Within the Cell
Specific Localization of Enzymes Within the cell
Which of the following is true of allosteric inhibitors of an enzyme?
 Grouped into complexes
 Present in the cytoplasm
A. Allosteric inhibitors bind to the active site of the enzyme.
 Incorporated into membranes
B. Allosteric inhibitors decrease enzyme activity.
 Contained inside organelles
C. Allosteric inhibitors are structurally similar to the normal substrate of
an enzyme.
D. The effect of allosteric inhibitors can be reduced by adding more
substrate.
E. Allosteric inhibitors increase the rate of enzyme activity.
Think/Pair/Share
Think/Pair/Share
Fill in the Blanks
Fill in the Blanks
Course of
reaction
without
enzyme
A
C
EA
without
enzyme
Reactants
E
B
Free energy
Free energy
D
EA with
enzyme
is lower
Reactants
G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Products
Progress of the reaction
Progress of the reaction
Enzyme Action!
You should be able to:
1.
2.
3.
4.
5.
6.
7.
8.
Distinguish between the following pairs of terms: catabolic and
anabolic pathways; kinetic and potential energy; open and closed
systems; exergonic and endergonic reactions
Explain the first and second law of thermodynamics
Explain in general terms how cells obtain the energy to do cellular
work
Explain how ATP performs cellular work
Explain why an investment of activation energy is necessary
to initiate a spontaneous reaction
Describe the mechanisms by which enzymes lower
activation energy
Describe how allosteric regulators may inhibit or stimulate
the activity of an enzyme
Explain what it means by feedback inhibition
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