Download 1. Energy & Chemical Reactions 2 Basic Forms of Energy 9/29/2015 Chapter 8:

9/29/2015
Chapter 8:
An Introduction to Metabolism
1. Energy & Chemical Reactions
2. ATP
3. Enzymes & Metabolic Pathways
1. Energy & Chemical Reactions
Chapter Reading – pp. 142-148
2 Basic Forms of Energy
Kinetic Energy (KE)
• energy in motion or “released” energy:
• heat (molecular motion)
• electric current* (flow of charged particles)
• light energy* (radiation of photons)
• mechanical energy* (structural movement)
• chemical energy* (breaking covalent bonds,
flow from high to low concentration)
*forms of KE cells use to “do things”
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Potential Energy (PE)
• stored energy (i.e., not yet released):
A diver has more potential
energy on the platform
than in the water.
Diving converts
potential energy to
kinetic energy.
• gravitational potential
• chemical bonds*
• chemical gradients*,
charge gradients*
Climbing up converts the kinetic
energy of muscle movement
to potential energy.
*sources of PE
cells rely on
A diver has less potential
energy in the water
than on the platform.
Illustration of Kinetic &
Potential Energy
KE highest at b, lowest at a & c
PE highest at
a & c, lowest at b
Laws of Energy Transformation
1st
Law of Thermodynamics
Principle of Conservation of Energy:
“Energy is neither created
nor destroyed, but may
be converted to other forms.”
Heat
CO2
+
Chemical
energy
(a) First law of thermodynamics
2nd
H2O
(b) Second law of thermodynamics
Law of Thermodynamics
• every energy conversion results in
a loss of usable energy as HEAT
“Every energy transfer or
transformation increases the
entropy of the universe.”
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Chemical Free Energy
Gibb’s Free Energy (G) = “chemical PE”
DG = Gproducts - Greactants
Negative DG:
• “loss” of chemical PE (e.g., respiration)
• net release of KE (for work or to raise temperature)
Positive DG:
• “gain” of chemical PE (e.g., photosynthesis)
• requires input of KE (e.g., sunlight)
DG = 0:
• system is at equilibrium
Examples of Spontaneous
Changes in Free Energy
• More free energy (higher G)
• Less stable
• Greater work capacity
In a spontaneous change
• The free energy of the system
decreases (DG  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
• in each case DG is negative and PE decreases
Reactants
• net release of energy
(DG is negative)
• loss of PE
Amount of
energy
released
(∆G < 0)
Free energy
Exergonic Reactions
Energy
Products
Progress of the reaction
(a) Exergonic reaction: energy released
Endergonic Reactions
• gain of PE
Free energy
• net consumption of
energy
(DG is positive)
Products
Amount of
energy
required
(∆G > 0)
Energy
Reactants
Progress of the reaction
(b) Endergonic reaction: energy required
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Activation Energy (EA)
Whether endergonic or exergonic, all chemical
reactions require some energy input for the reaction
to proceed – the
A
B
activation
C
D
energy (EA)
Transition state
A
B
C
D
• all reactions require
some sort of “spark”
EA
Reactants
A
B
C
D
∆G < O
Products
• this is why sources
of chemical PE are
“stable”
Progress of the reaction
Mechanical Model of
Activation Energy
The upright bottle falling over is analogous to an
exergonic reaction, yet it still requires some
energy input for the bottle to tip over.
2. ATP
Chapter Reading – pp. 148-151
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ATP – an Ideal Cellular Fuel
• useable amount of energy (DG -7.3 kcal/mole)
• stable, soluble in water (negatively charged)
• terminal
phosphoanhydride
bond easily
broken
ATP Hydrolysis
• exergonic cleavage of terminal phospho-anhydride bond
P
P
P
Adenosine triphosphate (ATP)
H2O
DG -7.3 kcal/mole)
P
i
+
P
Inorganic phosphate
P
+
Energy
Adenosine diphosphate (ADP)
The ATP Cycle
ATP
Energy from
catabolism (exergonic,
energy-releasing
processes)
+
H2O
ADP + P i
Energy for cellular
work (endergonic,
energy-consuming
processes)
Exergonic processes (e.g., cellular respiration) provide
energy for the endergonic synthesis of ATP, whereas
ATP hydrolysis releases energy that can be used for
other endergonic activities…
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Examples of ATP-powered “Work”
Membrane protein
P
P
i
Solute transported
Solute
(a) Transport work: ATP phosphorylates
transport proteins
ADP
+
ATP
P
Vesicle
Cytoskeletal track
i
ATP
Protein moved
Motor protein
(b) Mechanical work: ATP binds noncovalently
to motor proteins, then is hydrolyzed
Coupling of Biochemical Reactions
Exergonic reactions fuel (provide energy for)
endergonic reactions in cells (i.e, they are “coupled”)
• breakdown of
glucose fuels
ATP production
exergonic
endergonic
exergonic
endergonic
• ATP hydrolysis
fuels most
cellular activities
Example of Coupling w/ ATP Hydrolysis
(a) Glutamic acid
conversion
to glutamine
NH3
(b) Conversion
reaction
coupled
with ATP
hydrolysis
NH2
Glu
Glu
Glutamic
acid
DGGlu = +3.4 kcal/mol
Glutamine
Ammonia
NH3
P
1
Glu
ATP
Glu
ADP
2
Phosphorylated
intermediate
Glutamic
acid
NH2
Glu
ADP
Pi
Glutamine
DGGlu = +3.4 kcal/mol
(c) Free-energy
change for
coupled
reaction
NH3
Glu
DGGlu = +3.4 kcal/mol
+ DGATP = 7.3 kcal/mol
ATP
NH2
Glu
ADP
Pi
DGATP = 7.3 kcal/mol
Net DG = 3.9 kcal/mol
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3. Enzymes &
Metabolic Pathways
Chapter Reading – pp. 142, 151-159
Enzymes are Biological Catalysts
Biochemical reactions such as the one below will
not occur spontaneously without a catalyst:
Sucrase
Glucose
(C6H12O6)
Sucrose
(C12H22O11)
Fructose
(C6H12O6)
Enzymes are biological catalysts made of protein or
RNA that determine when reactions occur.
• the production and regulation of enzymes give a cell
complete control over all of the biochemical reactions
that occur within the cell
Enzymes Lower Activation Energy
Free energy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
DG is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
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Enzymes physically bind Substrates
Substrate
The “fit” of substrate
into active site is
highly specific and
due to molecular
complementarity
Active
sites
Enzyme
Enzyme-substrate
complex
• complementary in
physical shape
(“hand in glove”)
Substrate
Active
site
Enzyme-substrate
complex
Enzyme
• complementary in
chemical properties
(attraction between
opposite charges,
hydrophobic regions)
The Catalytic Cycle of Enzymes
1 Enzyme available
with empty active
site
Active site
• every enzyme has a
unique substrate &
thus catalyzes a
specific reaction
Substrate
(sucrose)
2 Substrate binds to
enzyme with induced fit
Glucose
Enzyme
(sucrase)
Fructose
H2O
4 Products are
released
3 Substrate is
converted to
products
• cells produce
1000s of different
enzymes, all of
which are proteins
encoded by a
particular gene
Factors effecting Enzyme Activity
Rate of reaction
Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
(heat-tolerant)
bacteria
40
0
60
100
20
80
Temperature (ºC)
(a) Optimal temperature for two enzymes
Rate of reaction
Optimal pH for pepsin
(stomach enzyme)
Optimal pH
for trypsin
(intestinal
enzyme)
4
5
6
0
1
2
3
pH
(b) Optimal pH for two enzymes
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Optimal temperature
and pH for a given
enzyme depend on the
environment in which
it normally functions
Deviation from the
optimal conditions can
result in denaturation
and loss of enzyme
activity
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Enzyme Regulation
Substrate
Active site
Competitive
inhibitor
Enzyme
Noncompetitive inhibitor
(c) Noncompetitive inhibition
(b) Competitive inhibition
(a) Normal binding
Enzymes can be regulated by inhibitors in two
general ways:
1) Competition between inhibitor & substrate for active site
2) Remotely inducing the active site to change shape
Competitive Enzyme Inhibition
Substrate
Competitive
inhibition
involves binding
of an inhibitor to
the active site
Competitive
inhibitor
Enzyme
Reversible
competitive
inhibitor
Enzyme
• inhibitor must be
reversible to be able
to regulate in
response to
concentration
Substrate
Increase in
substrate
concentration
irreversible inhibitors
essentially poison
the enzyme
Allosteric Enzyme Regulation
Allosteric
regulation
involves the
binding of a
substance to
an enzyme
outside the
active site
• induces change
in shape of
active site
• must be
reversible
Substrate
Distorted
active site
Enzyme
Active site
Allosteric site
Allosteric inhibition
Allosteric
inhibitor
(non-competitive)
Substrate
Distorted
active site
Active site
Allosteric site
Allosteric activator
Allosteric activation
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Cooperativity
With many multimeric enzymes, the binding of
substrate to one active site can stabilize the “active
conformation” of other active sites, thus increasing
the frequency with which they bind substrate.
Substrate
Stabilized active
form
Inactive form
• this is a type of
allosteric
regulation since
active sites are
regulated in a
non-competitive
manner
(b) Cooperativity: another type of allosteric activation
Metabolic Pathways
Most biological processes, whether anabolic
(building) or catabolic (breaking down), require
a series of chemical reactions (i.e., a pathway)
Enzyme 1
A
Enzyme 2
Enzyme 3
B
C
Reaction 1
Reaction 2
D
Reaction 3
Product
Starting
molecule
• each step in a metabolic pathway is catalyzed by a
specific enzyme
• a missing or inactive enzyme can prematurely shut
down a metabolic pathway, leading to the accumulation
of potentially dangerous intermediates
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 no
longer binds Intermediate B
threonine;
pathway is
Enzyme 3
switched off.
Intermediate C
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)
Feedback
Inhibition
The end-products of
metabolic pathways can
be important reversible
enzyme inhibitors
• inhibit 1st enzyme, turn
pathway “off”
low [inhibitor] = pathway ON
high [inhibitor] = pathway OFF
• can be competitive or
allosteric inhibition
• important way of regulating
end-product levels
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Key Terms for Chapter 8
• kinetic, potential energy, free energy
• endergonic, exergonic, coupling of reactions
• activation energy
• enzyme, catalyst
• substrate, active site, molecular complementarity
• competitive, noncompetitive, feedback inhibition
• allosteric, cooperative regulation
• reversible vs irreversible
Relevant
Chapter
Questions
1-7
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