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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
PowerPoint® Lecture Presentations for
Biology
Eighth Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp
An Introduction to
Metabolism
Chapter 8
What is metabolism?
• The sum of chemical reactions
within a living organism
• Metabolism is an emergent
property of life that arises from
interactions between molecules
within the cell
• An organism’s metabolism
transforms matter and energy,
subject to the laws of
thermodynamics
C6H12O6 + 6O2
6CO2 + 6H2O
+ energy e-
Overview: The Energy of Life
The living cell is a miniature chemical factory
where thousands of reactions occur
The cell extracts energy and uses energy to
perform work (e.g. breaking chemical bonds, movement)
Some organisms even convert energy to light,
as in bioluminescence
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Bioluminescence in deep-sea organisms
Organization of the Chemistry of Life into Metabolic Pathways
• Metabolism arranged into a series of
metabolic pathways beginning with a specific
molecule and ending with a product
• Each step is catalyzed by a specific enzyme
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Enzyme 1 Enzyme 2 Enzyme 3
D C B A Reaction 1 Reaction 3 Reaction 2
Starting molecule
Product
The mechanisms that regulate enzymes balance metabolic
supply and demand, adverting deficits or surpluses of
important cellular molecules.
Metabolism manages energy resources of the cell to make
it as efficient as possible
Generalized metabolic pathway
What Physical Principles Underlie Biological Energy Transformations?
Anabolic reactions: complex molecules are made from simple molecules; energy input is required.
Catabolic reactions: complex molecules are broken down to simpler ones and energy is released.
Metabolism = Catabolism and Anabolism
• Catabolic Reactions:
The breakdown of complex organic molecules into simpler molecules
Generally hydrolytic (Water added to break a bond)
exergonic (produce energy)-energy stored in chemical bonds is
released
Cellular respiration, the breakdown of glucose in the presence of
oxygen, is an example of a pathway of catabolism
• Anabolic Reactions:
The synthesis of complex organic molecules from simpler molecules
Generally dehydration synthesis reactions (water released when the
bond is formed)
Endergonic (consume energy)
The synthesis of protein from amino acids is an example of anabolism
• Energy is the capacity to cause change
• Energy exists in various forms.
• Energy can be converted from one form to
another (Examples of energy conversions?)
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Metabolism is transfer of energy
Energy Conversions
• All forms of energy can be converted into other forms.
The sun’s energy through solar cells can be
converted directly into electricity.
Green plants convert the sun’s energy
(electromagnetic energy) into starches and
sugars (chemical energy).
What Physical Principles Underlie Biological Energy Transformations?
All forms of energy can be placed in two
categories:
1) Potential energy is stored energy—as chemical
bonds, concentration gradient, charge imbalance,
etc.
• Chemical potential energy is energy available for release
in a chemical reaction (food is stored chemical energy)
2) Kinetic energy is the energy of movement.
• Heat (thermal energy) is kinetic energy associated with
• random movement of atoms or molecules
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.
Thermodynamic Systems - An overview
• A system is a group of interacting,
interrelated, or interdependent
elements forming a complex whole.
• Energy transfer is studied in two
types of systems:
– 1. Open systems
– 2. Closed systems (Isolated
systems)
Thermodynamics is the study of energy transformations
The Laws of Energy Transformation
• A closed (isolated) system
isolated from its surroundings
Unable to exchange either energy or matter with its surroundings
• Example: thermos
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The Laws of Energy Transformation
open systems
energy and matter transferred between the system and its surroundings.
Example: all organisms are open systems
– They absorb energy (light or chemical energy) in the for of organic molecules and release waste and metabolic products, such as CO2, to the surroundings.
What Physical Principles Underlie Biological Energy Transformations?
First Law of Thermodynamics: Energy
is neither created nor destroyed.
When energy is converted from one form
to another, the total energy before and
after the conversion is the same.
The first law is also called the principle of conservation
of energy
What Physical Principles Underlie Biological Energy Transformations?
Second Law of Thermodynamics: When energy is
converted from one form to another, some of that
energy becomes unavailable to do work.
No energy transformation is 100 % efficient.
Usually this energy is lost in the form of HEAT (= random energy of molecular
movement)
Example: only 25% of chemical energy stored in gasoline is transformed in to
motion of the car- 75% is lost as heat!!
The Second Law of Thermodynamics (stated in a different way)
•
According to the second law of thermodynamics:
Every energy transfer or transformation increases
the entropy (disorder or randomness) of the
Universe
THE UNIVERSE SPONTANEOUSLY GOES
TOWARDS “RANDOMNESS”
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All living systems obey the laws of thermodynamics
(a) First law of thermodynamics
Energy can be transferred or
transformed but neither created
or destroyed.
(b) Second law of thermodynamics
Every energy transfer or transformation increases the disorder
(entropy) of the universe.
Chemical energy
Heat
CO2
H2O
+
Fig. 8-4
50 µm
As open system, organisms can increase their order
as long as the order of their surroundings decrease.
What Physical Principles Underlie Biological Energy Transformations?
In any system:
total energy = usable energy + unusable energy
Enthalpy (H) = Free Energy (G) + Entropy (S)
or H = G + TS (T = absolute temperature)
G = H – TS
What Physical Principles Underlie Biological Energy Transformations?
Change in energy can be measured in
calories or joules.
Change in free energy (ΔG) in a reaction
is the difference in free energy of the
products and the reactants.
What Physical Principles Underlie Biological Energy Transformations?
ΔG = ΔH – TΔS
If ΔG is negative, free energy is released.
If ΔG is positive, free energy is consumed.
If free energy is not available, the reaction
does not occur.
What Physical Principles Underlie Biological Energy Transformations?
ΔG = ΔH – TΔS
Magnitude of ΔG depends on:
ΔH—total energy added (ΔH > 0) or
released (ΔH < 0).
ΔS—change in entropy. Large changes in
entropy make ΔG more negative.
What Physical Principles Underlie Biological Energy Transformations?
If a chemical reaction increases entropy,
the products will be more disordered.
Example: hydrolysis of a protein into its
component amino acids—ΔS is
positive.
What Physical Principles Underlie Biological Energy Transformations?
Exergonic reactions release free energy
(–ΔG)—catabolism
Endergonic reactions consume free
energy (+ΔG)—anabolism
What Physical Principles Underlie Biological Energy Transformations?
In principle, chemical reactions can run in
both directions.
Chemical equilibrium ΔG = 0
Forward and reverse reactions are
balanced.
BA
The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously
• Will the following reaction occur
Spontaneously????
• PO42- + glucose glucose-6-phosphate
• To do so, they need to determine energy
changes that occur in chemical reactions
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Spontaneous or not Spontaneous
• PO42- + glucose glucose-6-phosphate
Will NOT occur spontaneously!
WHY?
The change in energy between the reactants
(PO42- + glucose) and the products (glucose-6-
phosphate) measured and found that the
products contain more energy!
Only processes with a negative ∆G are
spontaneous (do not require energy input)
• Energy released in spontaneous processes
can be harnessed to perform work
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Spontaneous or not Spontaneous
Free Energy, Stability, and Equilibrium
• 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
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Fig. 8-5
(a) Gravitational motion (b) Diffusion (c) Chemical reaction
• 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
The relationship of free energy to stability, work capacity, and spontaneous change.
Unstable systems (top diagram) are rich in free energy, G. They have tendency to
change spontaneously to a more stable state (bottom), and it is possible to harness this
“downhill” change to perform work.
Free Energy and Metabolism
• The concept of free energy can be applied to
the chemistry of life’s processes
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Exergonic and Endergonic Reactions in Metabolism
• An exergonic reaction proceeds with a net
release of free energy and is spontaneous
(Negative ∆G )
• An endergonic reaction absorbs free energy
from its surroundings and is nonspontaneous
(Positive ∆G )
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Fig. 8-6 Free energy changes (∆G) in exergonic and endergonic reactions.
Reactants
Energy
Fre
e e
ne
rgy
Products
Amount of energy
released (∆G < 0)
Progress of the reaction
(a) Exergonic reaction: energy released
Products
Reactants
Energy
Fre
e e
ne
rgy
Amount of energy
required
(∆G > 0)
(b) Endergonic reaction: energy required
Progress of the reaction
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 defining feature of life is that metabolism is
never at equilibrium
• A catabolic pathway in a cell releases free energy
in a series of reactions
• Closed and open hydroelectric systems can serve
as analogies
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Fig. 8-7a
(a)An isolated hydroelectric system Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium.
∆G < 0 ∆G = 0
Fig. 8-7b
(b) An open hydroelectric system Flowing water keeps driving the generator because intake and outflow of water keep the system from reaching equilibrium.
∆G < 0
Fig. 8-7c
(c) A multistep open hydroelectric system Cellular respiration is analogous to this system. Glucose is broken down in a series of exergonic reactions that power the work of the cell. The product of each reaction Become the reactant for the next, so no reaction reach equilibrium.
∆G < 0
∆G < 0
∆G < 0
Equilibrium and Metabolism
• Reactions in a closed system eventually reach
equilibrium and then do no work.
• Cells and organism are not in equilibrium; they are
open systems experiencing a constant flow of
materials.
An Egyptian Mummy
Cellular work performed by coupling exergonic reactions to endergonic reactions
• A cell does three main kinds of work:
– Chemical
– Transport
– Mechanical
• How do cells get non-spontaneous reactions to occur?
• ……… by energy coupling, the use of an exergonic
process to drive an endergonic one
• Most energy coupling in cells is mediated by ATP
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The three
types of
cellular
work:
Mechanical,
Transport
and
Chemical
are powered
by the
hydrolysis of
ATP
The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate) is the cell’s energy
shuttle
• ATP is composed of ribose (a sugar), adenine
(a nitrogenous base), and three phosphate
groups
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Fig. 8-8 The structure of adenosine triphosphate (ATP)
Phosphate groups Ribose
Adenine
All three phosphate groups are negatively charged. These like charges are crowed together,
and their repulsion contributes to the instability of this region of the ATP molecule. The
triphosphate tail of ATP is the chemical equivalent of a compressed spring.
• 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
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The Structure and Hydrolysis of ATP
Fig. 8-9 The hydrolysis of ATP
Inorganic phosphate
Energy
Adenosine triphosphate (ATP)
Adenosine diphosphate (ADP)
P P
P P P
P + +
H2O
i
How ATP Performs Work
• The three types of cellular work (mechanical,
transport, and chemical) are powered by the
hydrolysis of ATP
• 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
(spontaneous)
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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
Fig. 8-11 How ATP drives transport and mechanical work
(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
• ATP is a renewable resource that is
regenerated by addition of a phosphate group
to adenosine diphosphate (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
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Fig. 8-12 The ATP cycle Energy released by breakdown reactions (catabolism) in the cell is used to phosphorylate ADP, regenerating ATP. Chemical potential energy stored in ATP drives most cellular work.
P i ADP +
Energy from catabolism (exergonic, energy-releasing processes)
Energy for cellular work (endergonic, energy-consuming processes)
ATP + H2O
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
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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
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Fig. 8-14 Energy profile of an exergonic reaction
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 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.
How Enzymes Lower the EA Barrier
• Enzymes catalyze reactions by lowering the EA
barrier of reaction
• An enzyme cannot change the ∆G for a reaction; it
cannot make an endorgonic reaction exergonic
Animation: How Enzymes Work
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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
• 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 fit is highly specific!
• The active site is the region on the enzyme where the
substrate binds
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The enzyme is NOT
changed in the
reaction
Substrate
Active site
Enzyme
Enzyme-substrate complex
(b) When the substrate enters the active site, it induces a change in the shape of the protein. This change allows active site to enfold the substrate and hold it in place
(a) The active site of this enzyme forms a groove on its surface.
Enzymes and substrates fit together like a hand
in a glove
Induced fit of a substrate brings chemical groups of the active
site into positions that enhance their ability to catalyze the
reaction
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
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Substrates
Enzyme
Products are released.
Products
Substrates are converted to products.
Active site can lower EA and speed up a reaction.
Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds.
Substrates enter active site; enzyme
changes shape such that its active site
enfolds the substrates (induced fit).
Active site is
available for two new
substrate molecules.
Enzyme-substrate complex
5
3
2
1
6
4
Fig. 8-17 The active site and catalytic cycle of an enzyme
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
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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
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Fig. 8-18 Environmental factors affecting enzyme activity
Ra
te o
f re
acti
on
Optimal temperature for enzyme of thermophilic
(heat-tolerant) bacteria
Optimal temperature for typical human enzyme
(a) Optimal temperature for two enzymes
(b) Optimal pH for two enzymes
Rate
of
reacti
on
Optimal pH for pepsin (stomach enzyme)
Optimal pH for trypsin (intestinal enzyme)
Temperature (ºC)
pH
5 4 3 2 1 0 6 7 8 9 10
0 20 40 80 60 100
Cofactors
• Some enzymes need a partner Cofactors
are nonprotein enzyme helpers
• Cofactors may be inorganic (such as a metal in
ionic form) or organic
• An organic cofactor is called a coenzyme
• Coenzymes include vitamins
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Enzyme Inhibitors
• Enzyme activity needs to be regulated
• 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
• Examples of inhibitors include toxins, poisons,
pesticides, and antibiotics
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(a) Normal binding A substrate can bind normally to the active site of an enzyme
(c) Noncompetitive inhibition binds to the enzyme away from the active site, altering the shape of the enzyme so that even the substrate can bind, the active site function less effective
(b) Competitive inhibition Mimics the substrate, competing for active site
Noncompetitive inhibitor
Active site
Competitive inhibitor
Substrate
Enzyme
Regulation of enzyme activity helps control metabolism
• Chemical chaos would result if a cell’s
metabolic pathways were not tightly regulated
• A cell does this by switching on or off the
genes that encode specific enzymes or by
regulating the activity of enzymes once
they are made
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Allosteric Regulation of Enzymes
• Allosteric regulation may either inhibit or
stimulate an enzyme’s activity
• Allosteric regulation occurs when a regulatory
molecule binds to a protein at one site and
affects the protein’s function at another site
– It may result in either inhibition or stimulation of
an enzyme’s activity
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Allosteric Activation and Inhibition
• 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
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Fig. 8-20 Allosteric regulation of enzyme activity.
Allosteric enyzme with four subunits
Active site (one of four)
Regulatory site (one of four)
Active form
Activator
Stabilized active form
Oscillation
Non- functional active site
Inhibitor Inactive form Stabilized inactive
form
(a) Allosteric activators and inhibitors
Substrate
Inactive form Stabilized active form
(b) Cooperativity: another type of allosteric activation
Fig. 8-20a
(a) Allosteric activators and inhibitors . In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.
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)
• 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
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Fig. 8-20b
(b) Cooperativity: another type of allosteric activation The inactive form shown on the left oscillates back and forth with the active form when the active form is not stability by substrate.
Stabilized active form
Substrate
Inactive form
Identification of Allosteric Regulators
• Allosteric regulators are attractive drug
candidates for enzyme regulation
• Inhibition of proteolytic enzymes called
caspases may help management of
inappropriate inflammatory responses
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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
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Fig. 8-22 Feedback inhibition in isoleucine synthesis.
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
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
• In eukaryotic cells, some enzymes reside in
specific organelles; for example, enzymes for
cellular respiration are located in mitochondria
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You should now 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
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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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