Energy and Metabolism

1
 The Energy of Life
• The living cell generates thousands of
different reactions
• Metabolism
• Is the totality of an organism’s chemical
reactions
• Arises from interactions between
molecules
• An organism’s metabolism transforms matter
and energy, subject to the laws of
thermodynamics
2
 Metabolic Pathways
• Biochemical pathways are the organizational units of metabolism
• Metabolism is the total of all chemical reactions carried out by an
organism
• A metabolic pathway has many steps that begin with a specific
molecule and end with a product, each catalyzed by a specific enzyme
• Reactions that join small molecules together to form larger, more
complex molecules are called anabolic.
• Reactions that break large molecules down into smaller subunits are
called catabolic.

Enzyme 1 Enzyme 2 Enzyme 3

A B C D
Reaction 1 Reaction 2 Reaction 3
Starting Product
molecule
3
 Metabolic Pathway
• A sequence of chemical reactions, where the product of
one reaction serves as a substrate for the next, is called a
metabolic pathway or biochemical pathway
• Most metabolic pathways take place in specific regions of
the cell.

4
 Bioenergetics

• Bioenergetics is the study of how organisms

manage their energy resources via
metabolic pathways
• Catabolic pathways release energy by
breaking down complex molecules into
simpler compounds
• Anabolic pathways consume energy to build
complex molecules from simpler ones

5
 Energy
• Energy is the capacity to do work or ability to
cause change. Any change in the universe
requires energy. Energy comes in 2 forms:
• Potential energy is stored energy. No
change is currently taking place
• Kinetic energy is currently causing
change. This always involves some type
of motion.

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 Forms of Energy
• Kinetic energy is the
On the platform, a diver
has more potential energy.
Diving converts potential
energy to kinetic energy.

energy associated with

motion
• Potential energy
• Is stored in the
location of matter
• Includes chemical
energy stored in
molecular structure
• Energy can be converted
from one form to another Climbing up converts kinetic In the water, a diver has
energy of muscle movement less potential energy.

to potential energy.

7
 Laws of Energy Transformation
• Thermodynamics is the study of energy
changes.
• Two fundamental laws govern all energy
changes in the universe. These 2 laws are
simply called the first and second laws of
thermodynamics:

8
 The First Law of Thermodynamics
• According to the first law of thermodynamics
• Energy cannot be created or destroyed
• Energy can be transferred and transformed

Chemical
energy

For example, the chemical (potential) energy

in food will be converted to the kinetic
energy of the cheetah’s movement

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 Second Law of Thermodynamics
• The disorder (entropy) in the universe is continuously increasing.
• Energy transformations proceed spontaneously to convert matter from a
more ordered, less stable form, to a less ordered, more stable form
• Spontaneous changes that do not require outside energy increase the
entropy, or disorder, of the universe
• For a process to occur without energy input, it must increase the entropy of
the universe

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 Second Law of Thermodynamics
• During each conversion, some of the energy dissipates into the
environment as heat.
• During every energy transfer or transformation, some energy is
unusable, often lost as heat
• Heat is defined as the measure of the random motion of molecules
• Living cells unavoidably convert organized forms of energy to heat
• According to the second law of thermodynamics, every energy transfer
or transformation increases the entropy (disorder) of the universe

Heat co2
+
H2O

For example, disorder is added to the cheetah’ssurroundings in the form of heat

and the small molecules that are the by-products of metabolism.
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 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
• The evolution of more complex organisms does
not violate the second law of thermodynamics
• Entropy (disorder) may decrease in an
organism, but the universe’s total entropy
increases

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 Biological Order and Disorder
• Living systems
• Increase the entropy of the universe
• Use energy to maintain order
• A living system’s free energy is energy that can
do work under cellular conditions
• Organisms live at the expense of free energy
50µm

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 Free Energy
• Free energy is the portion of a system’s energy that is able
to perform work when temperature and pressure is uniform
throughout the system, as in a living cell
• Free energy also refers to the amount of energy actually
available to break and subsequently form other chemical
bonds
• Gibbs’ free energy (G) – in a cell, the amount of energy
contained in a molecule’s chemical bonds (T&P constant)
• Change in free energy - ΔG
• Endergonic - any reaction that requires an input of
energy
• Exergonic - any reaction that releases free energy

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 Exergonic reactions
• Reactants have more free energy than the products
• Involve a net release of energy and/or an increase in
entropy
• Occur spontaneously (without a net input of energy)

Reactants

Amount of
energy
released
Free energy

(∆G <0)
Energy
Products

Progress of the reaction

(a) Exergonic reaction: energy released

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 Endergonic Reactions
• Reactants have less free energy than the products
• Involve a net input of energy and/or a decrease in
entropy
• Do not occur spontaneously
Products

Amount of
energy
Free energy

released
(∆G>0)
Energy
Reactants

Progress of the reaction

(b) Endergonic reaction: energy required

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Energy released Energy supplied

Product

Energy
must be
supplied.

Reactant Reactant Energy is

released.

Product
Endergonic Exergonic

17
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 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 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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 Equilibrium and Metabolism
• Reactions in a closed system eventually reach equilibrium
∆G < 0 ∆G = 0

(a) A closed 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.

• Cells in our body experience a constant flow of materials

in and out, preventing metabolic pathways from reaching
equilibrium

(b) An open hydroelectric

∆G < 0
system. Flowing water
keeps driving the generator
because intake and outflow
of water keep the system
from reaching equlibrium.

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An Analogy For Cellular Respiration –
Glucose Catabolism

∆G < 0
∆G < 0

∆G < 0

(c) A multistep open hydroelectric system. Cellular respiration is

analogous to this system: Glucoce is brocken down in a series
of exergonic reactions that power the work of the cell. The product
of each reaction becomes the reactant for the next, so no reaction
reaches equilibrium.

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 Energy Coupling
• Living organisms have the ability to couple
exergonic and endergonic reactions:
• Energy released by exergonic reactions is
captured and used to make ATP from ADP
and Pi
• ATP can be broken back down to ADP and
Pi, releasing energy to power the cell’s
endergonic reactions.

21
 The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate)
• Is the cell’s energy shuttle
• Provides energy for cellular functions
Adenine NH2

N C
C N
O O O HC
CH
C
-O O O O CH2
O
N
N

O - O - O -
H H
Phosphate groups H
Ribose
H
OH OH

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 The Structure and Hydrolysis of ATP
• Energy is released from ATP when the terminal phosphate
bond is broken

P P P

Adenosine triphosphate (ATP)

H2O

P i
+ P P Energy

Inorganic phosphate Adenosine diphosphate (ADP)

23
 Cellular Work
• A cell does three main kinds of work
• Mechanical
• Transport
• Chemical
• Energy coupling is a key feature in the way cells
manage their energy resources to do this work
• ATP powers cellular work by coupling exergonic
reactions to endergonic reactions

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 Energy Coupling - ATP / ADP Cycle
• Releasing the third phosphate from ATP to make ADP generates
energy (exergonic):
• Linking the phosphates together requires energy - so making ATP from
ADP and a third phosphate requires energy (endergonic),
• Catabolic pathways drive the regeneration of ATP from ADP and
phosphate
ATP synthesis from ATP hydrolysis to
ADP + P i requires energy ADP + P i yields energy

ATP

Energy from catabolism Energy for cellular work

(exergonic, energy yielding (endergonic, energy-
processes) consuming processes)
ADP + P i
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 How ATP Performs Work

• ATP drives endergonic reactions by

phosphorylation, transferring a phosphate group
to some other molecule, such as a reactant
• The recipient molecule is now phosphorylated
• The three types of cellular work (mechanical,
transport, and chemical) are powered by the
hydrolysis of ATP

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 How ATP Performs Work
• ATP drives endergonic reactions by phosphorylation, transferring a
phosphate to other molecules - hydrolysis of ATP

P i
P

Motor protein Protein moved

(a) Mechanical work: ATP phosphorylates motor proteins

Membrane
protein
ADP
ATP +
P i

P P i

Solute Solute transported

(b) Transport work: ATP phosphorylates transport proteins

P
NH2
Glu + NH3 + P i

Glu
Reactants: Glutamic acid Product (glutamine)
and ammonia made

(c) Chemical work: ATP phosphorylates key reactants 27

 Activation Energy
• All reactions, both endergonic and exergonic, require an input of energy to
get started. This energy is called activation energy
• The activation energy, EA
• Is the initial amount of energy needed to start a chemical reaction
• Activation energy is needed to bring the reactants close together and weaken
existing bonds to initiate a chemical reaction.
• Is often supplied in the form of heat from the surroundings in a system.

A B

C D
Transition state

A B EA
Free energy

C D

Reactants
A B
∆G < O
C D

Products
Progress of the reaction
28
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Reaction Rates
• In most cases, molecules do not have enough
kinetic energy to reach the transition state when
they collide.
• Therefore, most collisions are non-productive, and
the reaction proceeds very slowly if at all.
• What can be done to speed up these reactions?

29
 Increasing Reaction Rates
• Add Energy (Heat) - molecules move faster so they collide
more frequently and with greater force.
• Add a catalyst – a catalyst reduces the energy needed to
reach the activation state, without being changed itself.
Proteins that function as catalysts are called enzymes.

Activation Energy and Catalysis

Energy supplied

Activation
energy

Activation
energy
Energy released

Reactant Reactant

Product Product

Uncatalyzed Catalyzed
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Enzymes Lower the EA Barrier
• An enzyme catalyzes reactions by lowering
the EA barrier

Course of
reaction EA
without
without
enzyme
enzyme
EA with
enzyme
is lower
Reactants
Free energy

Course of ∆G is unaffected
reaction by enzyme
with enzyme

Products

Progress of the reaction 31

 Enzymes Are Biological Catalysts
• Enzymes are proteins that carry out most catalysis in living
organisms.
• Unlike heat, enzymes are highly specific. Each enzyme
typically speeds up only one or a few chemical reactions.
• Unique three-dimensional shape enables an enzyme to
stabilize a temporary association between substrates.
• Because the enzyme itself is not changed or consumed in
the reaction, only a small amount is needed, and can then
be reused.
• Therefore, by controlling which enzymes are made, a cell
can control which reactions take place in the cell.

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 Substrate Specificity of Enzymes
• Almost all enzymes are globular proteins with one or more active sites on their
surface.
• The substrate is the reactant an enzyme acts on
• Reactants bind to the active site to form an enzyme-substrate complex.
• The 3-D shape of the active site and the substrates must match, like a lock and key
• Binding of the substrates causes the enzyme to adjust its shape slightly, leading to
a better induced fit.
• Induced fit of a substrate brings chemical groups of the active site into positions
that enhance their ability to catalyze the chemical reaction
• When this happens, the substrates are brought close together and existing bonds
are stressed. This reduces the amount of energy needed to reach the transition
state.

Substate

Active site

Enzyme- substrate
Enzyme complex
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 The Catalytic Cycle Of An Enzyme

1 Substrates enter active site; enzyme

changes shape so its active site 2 Substrates held in
embraces the substrates (induced fit). active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.

3 Active site (and R groups of

Substrates Enzyme-substrate its amino acids) can lower EA
complex and speed up a reaction by
• acting as a template for
substrate orientation,
6 Active site • stressing the substrate bonds
s available for and stabilizing the
wo new substrate transition state,
Mole. • providing a favorable
microenvironment,
Enzyme
• participating directly in the
catalytic reaction.

5 Products are
Released. 4 Substrates are
Converted into 34
Figure 8.17 Products Products.
 The Catalytic Cycle Of An Enzyme

1 The substrate, sucrose, consists

of glucose and fructose bonded together.
Glucose Fructose

2 The substrate binds to the enzyme,

forming an enzyme-substrate
complex.
Bond 4 Products are
H2O released, and the
enzyme is free to
bind other
substrates.

Active site 3 The binding of the substrate

and enzyme places stress on
the glucose-fructose bond,
and the bond breaks.
Enzyme

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 Factors Affecting Enzyme Activity
• Temperature - rate of an enzyme-catalyzed
reaction increases with temperature, but only
up to an optimum temperature.
• pH - ionic interactions also hold enzymes
together.
• Inhibitors and Activators

36
 Effects of Temperature and pH
• Each enzyme has an optimal temperature in
which it can function
Optimal temperature for Optimal temperature for
typical human enzyme enzyme of thermophilic
(heat-tolerant)
bacteria
Rate of reaction

0 20 40 80 100
Temperature (Cº)
(a) Optimal temperature for two enzymes

37
 Effects of Temperature and pH
• Each enzyme has an optimal pH in which it can
function

Optimal pH for pepsin Optimal pH

(stomach enzyme) for trypsin
(intestinal
Rate of reaction

enzyme)

0 1 2 3 4 5 6 7 8 9
(b) Optimal pH for two enzymes

Figure 8.18
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 Factors Affecting Enzyme Activity
• Inhibitor - substance that binds to an enzyme
and decreases its activity – feedback
• Competitive inhibitors - compete with the
substrate for the same active site
• Noncompetitive inhibitors - bind to the
enzyme in a location other than the active
site
• Allosteric sites - specific binding sites
acting as on/off switches

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 Enzyme Inhibitors
• Competitive inhibitors bind to the active site of an enzyme,
competing with the substrate

A substrate can
Substrate
bind normally to the
active site of an
enzyme. Active site

Enzyme

(a) Normal binding

A competitive
inhibitor mimics the Competitive
substrate, competing inhibitor
for the active site.

(b) Competitive inhibition

40
 Enzyme Inhibitors
• 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
(c) Noncompetitive inhibition

41
 Regulation Of Enzyme Activity Helps
Control Metabolism
• Chemical chaos would result if a cell’s metabolic
pathways were not tightly regulated
• To regulate metabolic pathways, the cell switches
on or off the genes that encode specific 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
• Enzymes change shape when regulatory
molecules bind to specific sites, affecting function

42
 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

43
 Allosteric Regulation of Enzymes
• Allosteric regulation may either inhibit or stimulate an
enzyme’s activity
Allosteric activater
Allosteric enyzme stabilizes active from
Active site
with four subunits (one of four)

Regulatory
site (one
of four) Activator
Active form Stabilized active form

Allosteric activater
stabilizes inactive form
Oscillation

Non- Inactive form Inhibitor Stabilized inactive

functional form
active
site

(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors
dissociate when at low concentrations. The enzyme can then oscillate again. 44
 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 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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 Factors Affecting Enzyme Activity

• Activators - substances that bind to allosteric

sites and keep the enzymes in their active
configurations - increases enzyme activity
• Cofactors - chemical components that
facilitate enzyme activity
• Coenzymes - organic molecules that
function as cofactors

46
 Regulation of Biochemical Pathways
• Biochemical pathways must be coordinated
and regulated to operate efficiently.
• Advantageous for cell to temporarily shut
down biochemical pathways when their
products are not needed
• Feedback Inhibition

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 Feedback Inhibition
Initial substrate
• In feedback inhibition the Active site
(threonine)

end product of a metabolic available

Threonine
in active site

pathway shuts down the Enzyme 1

(threonine
pathway Isoleucine
used up by
deaminase)
cell
• When the cell produces Intermediate A
Feedback
increasing quantities of a inhibition
Active site of
enzyme 1 no
Enzyme 2

longer binds
particular product, it threonine;
pathway is
Intermediate B

automatically inhibits its switched off Enzyme 3

ability to produce more Isoleucine

Intermediate C

binds to Enzyme 4
allosteric
site Intermediate D

Enzyme 5

End product
(isoleucine)
48