Intro to Metabolism
Chapter 8
Overview: The Energy of Life
Thousands of chemical reactions occur
inside of a cell; cells = mini factories
 The cell extracts energy and applies
energy to perform work
 Many examples of energy conversion

◦ Chemical  kinetic
◦ Light  chemical
◦ Chemical  light
What other examples of bioluminescence can you think of?
What adaptive advantage does bioluminescence provide?
Energy Transformation

Metabolism - totality of an organism’s
chemical reactions
◦ an emergent property of life that arises from
interactions between molecules within the cell
Metabolic Pathways
Begin with specific molecule (reactant)
 End with specific product
 Each step is catalyzed by a specific
enzyme

LE 8-UN141
Enzyme 1
A
B
Reaction 1
Starting
molecule
Enzyme 2
Enzyme 3
D
C
Reaction 2
Reaction 3
Product
Metabolism

Bioenergetics - study of how
organisms manage their energy resources

Catabolic pathways - release energy by
breaking down complex molecules into
simpler compounds

Anabolic pathways - consume energy to
build complex molecules from simpler
ones
Forms of Energy
Energy - capacity to cause change
(usually to do work)
 Energy exists in various forms, some of
which can perform work

◦
◦
◦
◦
◦
Chemical
Kinetic
Potential
Thermal
Light
LE 8-2
On the platform,
the diver has
more potential
energy.
Diving converts
potential
energy to
kinetic energy.
Climbing up converts
kinetic energy of
muscle movement to
potential energy.
In the water, the
diver has less
potential energy.
The Laws of Energy
Transformation

Thermodynamics - study of energy
transformations

Closed system - isolated from its
surroundings (liquids inside of a thermos)

Open system - energy & matter can be
transferred between the system & its
surroundings
Are organisms open or closed systems?
The First Law of Thermodynamics

Energy of the universe is constant
◦ Energy can be transferred & transformed but
not made or destroyed

Also called the principle of conservation of
energy
The Second Law of
Thermodynamics




During every energy transfer or
transformation, some energy is unusable,
often lost as heat
Every energy transfer leads to an increase in
entropy in the universe
Entropy (S) – a measure of disorder that
accounts for randomness
Positive entropy  spontaneous reactions
How do nonspontaneous chemical reactions
occur?
LE 8-3
Heat
Chemical
energy
First law of thermodynamics
CO2
H2O
Second law of thermodynamics
Biological Entropy
Living cells unavoidably convert organized
forms of energy to heat
 Spontaneous processes occur without
energy input; they can happen quickly or
slowly
 For a process to occur without energy
input, it must increase the entropy of the
universe

Biological Order and Disorder
Cells create ordered structures from less
ordered materials
 Organisms also replace ordered forms of
matter & energy with less ordered forms
 The evolution of more complex organisms
does not violate the 2nd law of
thermodynamics
 Entropy (disorder) may ↓ in an organism,
but the universe’s total entropy ↑’s

Free Energy (ΔG)
Which metabolic processes are
spontaneous?
 To find out, we must calculate changes in
energy for chemical reactions
 A living system’s free energy – energy
that can do work when temperature &
pressure are uniform, as in a living cell

Free Energy
The change in free energy (∆G) during a
process is related to the change in
enthalpy, or change in total energy (∆H),
and change in entropy (T∆S):
∆G = ∆H - T∆S
 Only processes with a negative ∆G are
spontaneous
 Spontaneous processes can be harnessed
to perform work

∆G = ∆H - T∆S




∆G = Change in Gibbs free energy
∆H = Change in enthalpy
T = Temperature (K)
∆S = Change in entropy
Enthalpy = heat/energy of a system
(internal energy + PxV)
 If ∆G < 0, the reaction is spontaneous
 If ∆G > 0, the reaction is nonspontaneous

Free Energy, Stability, and
Equilibrium

Free energy - measure of a system’s
instability; its tendency to change to a more
stable state

During spontaneous change, free energy
decreases & the stability of a system
increases

Equilibrium - state of maximum stability

A process is spontaneous & can perform work
only when it is moving toward equilibrium
LE 8-5
Gravitational motion
Diffusion
Chemical reaction
Brainstorm
Why is the concept of free energy so
important when we are studying metabolic
processes?
Video
Free energy and metabolism

Exergonic reaction - net release of free
energy; spontaneous
◦ Cellular respiration – products store amount of
energy less than reactants equal to amount of
energy released by reaction

Endergonic reaction - absorbs free energy
from its surroundings; nonspontaneous
◦ Stores free energy (positive ΔG)

If a reaction is exergonic, the reverse
reaction must be endergonic
LE 8-6a
Free energy
Reactants
Amount of
energy
released
(G < 0)
Energy
Products
Progress of the reaction
Exergonic reaction: energy released
LE 8-6b
Free energy
Products
Energy
Reactants
Progress of the reaction
Endergonic reaction: energy required
Amount of
energy
required
(G > 0)
Equilibrium and Metabolism
Reactions in a closed system eventually
reach equilibrium & then do no work
 Cells are not in equilibrium; open systems
with constant flow of materials
 A catabolic pathway in a cell releases free
energy in a series of reactions

LE 8-7a
G < 0
A closed hydroelectric system
G = 0
LE 8-7b
G < 0
An open hydroelectric system
LE 8-7c
G < 0
G < 0
G < 0
A multistep open hydroelectric system
ATP, exergonic, and endergonic
reactions

Cells do 3 main kinds of work:
◦ Mechanical
◦ Transport
◦ Chemical

To do work, cells manage energy
resources by energy coupling - using an
exergonic process to drive an endergonic
one
The Structure and Hydrolysis of
ATP
ATP (adenosine triphosphate) is the cell’s
energy shuttle
 ATP provides energy for cellular functions

Ribose
ATP
Bonds between the phosphate groups of
ATP’s tail can be broken by hydrolysis;
energy released from ATP
 Energy is released from ATP when the
terminal phosphate bond is broken
 Release of energy comes from chemical
change to a state of lower free energy,
not from the phosphate bonds themselves

LE 8-9
P
P
P
Adenosine triphosphate (ATP)
H2O
Pi
+
Inorganic phosphate
P
P
Adenosine diphosphate (ADP)
+
Energy
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

LE 8-10
Endergonic reaction: G is positive, reaction
is not spontaneous
NH2
Glu
+
NH3
Ammonia
Glutamic
acid
G = +3.4 kcal/mol
Glu
Glutamine
Exergonic reaction: G is negative, reaction
is spontaneous
ATP
+
H2O
ADP
Coupled reactions: Overall G is negative;
together, reactions are spontaneous
+
Pi
G = –7.3 kcal/mol
G = –3.9 kcal/mol
How ATP Performs Work
ATP drives endergonic reactions by
phosphorylation, transferring a P group to
some other molecule (reactant)
 recipient molecule is now phosphorylated
 The 3 types of cellular work (mechanical,
transport, and chemical) are powered by
the hydrolysis of ATP

Review: Explain the process of hydrolysis.
LE 8-11
Pi
P
Motor protein
Protein moved
Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
Pi
ATP
Pi
P
Solute transported
Solute
Transport work: ATP phosphorylates transport proteins
P
NH2
Glu
+
NH3
+
Pi
Glu
Reactants: Glutamic acid
and ammonia
Product (glutamine)
made
Chemical work: ATP phosphorylates key reactants
The Regeneration of ATP

ATP - renewable resource regenerated by
adding a P group to ADP

energy to phosphorylate ADP comes from
catabolic reactions in cell

chemical potential energy temporarily
stored in ATP drives most cell work
LE 8-12
ATP
Energy for cellular work
(endergonic, energyconsuming processes)
Energy from catabolism
(energonic, energyyielding processes)
ADP +
P
i
Enzymes
Catalyst - chemical agent that speeds up
a reaction without being consumed
 Enzyme - catalytic protein
 Hydrolysis of sucrose by the enzyme
sucrase is an example of an enzymecatalyzed reaction

LE 8-13
Sucrose
C12H22O11
Glucose
C6H12O6
Fructose
C6H12O6
The Activation Energy Barrier
Every chemical reaction involves bond
breaking & bond forming
 Initial energy needed to start a chemical
reaction is called the free energy of
activation, or activation energy (EA)
 Activation energy(EA) - energy needed to
start a reaction; often supplied in the
form of heat from the surroundings

LE 8-14
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
How Enzymes Lower the EA
Barrier

Enzymes catalyze reactions by lowering
the EA barrier

Enzymes don’t affect the change in freeenergy (∆G); instead, they speed up
reactions that would occur eventually
LE 8-15
Free energy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
Course of
reaction
with enzyme
G is unaffected
by enzyme
Products
Progress of the reaction
Substrate Specificity of Enzymes
Substrate - reactant an enzyme acts on
 Enzyme binds to its substrate, forming an
enzyme-substrate complex
 Active site - on enzyme where the
substrate binds
 Induced fit of a substrate brings chemical
groups of the active site into positions
that enhance their ability to catalyze the
reaction

LE 8-16
Substrate
Active site
Enzyme
Enzyme-substrate
complex
Catalysis in the Enzyme’s Active
Site
In an enzymatic reaction, the substrate
binds to the active site
 Active site lowers EA barrier by

◦
◦
◦
◦
Orienting substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Covalently bonding to the substrate
LE 8-17
Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
Substrates
Enzyme-substrate
complex
Active
site is
available
for two new
substrate
molecules.
Enzyme
Products are
released.
Substrates are
converted into
products.
Products
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.
Effects of Local Conditions on
Enzyme Activity

Enzyme activity affected by:
◦ Temperature and pH
◦ Chemicals
◦ Substrate concentration
Effects of Temperature and pH
Each enzyme has an optimal temperature
& an optimal pH
 Most enzymes that affect humans operate
best at 35-40˚C
 Optimal pH for most enzymes is 6-8

LE 8-18
Optimal temperature for
typical human enzyme
0
Optimal temperature for
enzyme of thermophilic
(heat-tolerant
bacteria)
40
60
Temperature (°C)
20
80
100
Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach enzyme)
0
1
2
3
4
Optimal pH
for trypsin
(intestinal
enzyme)
5
pH
Optimal pH for two enzymes
6
7
8
9
10
Cofactors
Cofactors - nonprotein enzyme helpers;
minerals
 Coenzymes- organic cofactors; vitamins

Enzyme Inhibitors
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 & making the
active site less effective

LE 8-19
A substrate can
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
Competitive
inhibitor
Competitive inhibition
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
Noncompetitive inhibition
Regulation of Enzyme Activity
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 of Enzymes

Allosteric regulation - a protein’s function
at 1 site is affected by binding of a
regulatory molecule at another site; can
either inhibit or stimulate an enzyme’s
activity
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

LE 8-20a
Allosteric enzyme
with four subunits
Regulatory
site (one
of four)
Active site
(one of four)
Activator
Active form
Oscillation
Nonfunctional
active site
Allosteric activator
stabilizes active form.
Inactive form
Stabilized active form
Allosteric inhibitor
stabilizes inactive form.
Inhibitor
Allosteric activators and inhibitors
Stabilized inactive
form
Allosteric Regulation
Cooperativity is a form of allosteric
regulation that can amplify enzyme
activity
 Cooperativity - binding by a substrate to 1
active site stabilizes favorable
conformational changes at all other
subunits

LE 8-20b
Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.
Substrate
Inactive form
Stabilized active form
Cooperativity another type of allosteric activation
Feedback Inhibition
Feedback inhibition - 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

What kind of feedback loop is this an
example of?
LE 8-21
Initial substrate
(threonine)
Active site
available
Isoleucine
used up by
cell
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Intermediate A
Feedback
inhibition
Enzyme 2
Active site of
enzyme 1 can’t
bind
Intermediate B
theonine
pathway off
Enzyme 3
Isoleucine
binds to
allosteric
site
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)
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
 Some enzymes reside in specific
organelles, such as enzymes for cellular
respiration being located in mitochondria

LE 8-22
Mitochondria,
sites of cellular respiration
1 µm