Transcript 10 Metabolism

An Introduction to
Metabolism
chapter 8
1
Energy & Matter
Universe is composed of 2 things ……
Energy

Ability to do work
o
Force on an object that causes it to move
Matter
Anything that has mass and occupies space
 Atoms/elements

2
Metabolism
transforming matter and energy
 Metabolism -- totality of an organism’s chemical
reactions

Arises from interactions between molecules within the cell
3
Organization of the Chemistry of
Life into Metabolic Pathways
 A metabolic pathway begins with a specific
molecule and ends with a product
 Each step is catalyzed by a specific enzyme
Enzyme 1
A
B
Reaction 1
Starting
molecule
Enzyme 2
Enzyme 3
D
C
Reaction 2
Reaction 3
Product
4
Kinds of Pathways
 Catabolic pathways -- release energy

break down complex molecules into simpler compounds
 Anabolic pathways -- consume energy

build complex molecules from simpler ones
 Bioenergetics -- study of how organisms manage their
energy resources
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6
Chemical Reactions
Functionality
Catabolic
 Anabolic

Energy Requirements
Endergonic
 Exergonic

7
Chemical Reactions
 Reactions can be categorized as exergonic or
endergonic based on energy gain or loss
 Chemical reactions require initial energy input
(activation energy)


Molecules need to be moving with sufficient
collision speed
The electrons of an atom repel other atoms and
inhibit bond formation
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Energy
The ability to do work
Work -- force on an object that causes it to move
 What’s moving?

Two kinds of energy
Kinetic
 Potential – can be positional

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What Is Energy?
The two fundamental types

Kinetic -- energy of movement
o

Heat (thermal energy) -- random movement of
atoms or molecules
Potential -- stored energy (can be because of
location!)
o
Chemical energy -- available for release in a chemical
reaction
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Overview: The Energy of Life
Living cell -- miniature chemical factory
Energy transformed and stored
Energy observed in many forms
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The Laws of Energy
Transformation
Thermodynamics -- study of energy
transformations

Describe availability & usefulness of energy
Closed system -- isolated from its surroundings
Open system -- energy and matter can be
transferred between the system and its
surroundings
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Closed and open hydroelectric systems can serve as analogies
G < 0
G = 0
A closed hydroelectric system
G < 0
An open hydroelectric system
Laws of Thermodynamics
First -- In any process, the total energy of the
universe remains constant.
 Principle
of conservation of energy
 Energy
can be transferred and transformed
 Energy cannot be created or destroyed
Second -- The entropy of an isolated system
not in equilibrium will tend to increase over
time, approaching a maximum value at
equilibrium.

During every energy transfer or transformation, energy
is “lost” (the amount of useable energy decreases;
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disorder increases)
Thermodynamics
15
16
Entropy
Entropy – randomness

Energy conversions increase entropy in the universe
Spontaneous processes increase entropy

Explosions; car rusting
Non-spontaneous process – energy input

Rocks rolling uphill
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Enthalpy
Enthalpy (H) – total potential energy of system

Total energy = Usable Energy + Unusable Energy
Entropy (S) – randomness or disorder (unusable
energy)
Free Energy (G) – energy available to do work
ΔG -- change in free energy
 ΔG = ΔGfinal – ΔGinitial
 A negative ΔG – spontaneous

Note – as entropy increases, free energy decreases
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Free Energy & Stability
19
Exergonic Reactions
 Exergonic reactions release energy

Reactants contain more energy than products
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Exergonic Reactions
 Exergonic reactions release energy

Reactants contain more energy than products
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Endergonic Reactions
Endergonic reactions require an input of energy

Products contain more energy than reactants
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Endergonic Reactions
Endergonic reactions require an input of energy

Products contain more energy than reactants
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Coupled Reactions
Exergonic reactions drive endergonic reactions

The product of an energy-yielding reaction fuels an
energy-requiring reaction in a coupled reaction
The parts of coupled reactions often occur at
different places within the cell
Energy-carrier molecules transfer the energy
within cells
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ATP powers cellular work by
coupling exergonic reactions to
endergonic reactions
 Cells do work:
Mechanical
 Transport
 Chemical

 Cells manage energy resources by energy coupling: the
use of an exergonic process to drive an endergonic
one
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The Structure and Hydrolysis of
ATP
 ATP (adenosine triphosphate) -- cell’s energy
shuttle
 ATP provides energy for cellular functions
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Hydrolysis of ATP
 High energy phosphate bonds -- broken by hydrolysis
 Energy release -- chemical change to a state of lower free
energy, not from the phosphate bonds themselves
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 Energy from ATP hydrolysis can be used to drive
an endergonic reaction

Overall, the coupled reactions are exergonic
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Phosphorylation
Pi
P
Protein moved
Motor protein
Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
Pi
ATP
Pi
P
Solute
Solute transported
Transport work: ATP phosphorylates transport proteins
P
NH3
Glu +
NH2
Glu
+ Pi
Reactants: Glutamic acid Product (glutamine)
and ammonia
made
Chemical work: ATP phosphorylates key reactants
The Regeneration of ATP
 ATP -- renewable resource

regenerated by addition of a phosphate group to ADP
The energy comes from catabolic reactions in the cell
The potential energy stored in ATP drives most
cellular work
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LE 8-12
ATP
Energy from catabolism
(exergonic, energyyielding processes)
Energy for cellular work
(endergonic, energyconsuming processes)
ADP +
P
i
Exergonic Reactions
 Exergonic reactions release energy

Spontaneous?
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The Activation Energy Barrier
 Chemical reactions -- bond breaking and bond
forming
 The initial energy -- free energy of activation, or
activation energy (EA)
 EA often supplied in the form of heat from the
surroundings
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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 Catalyze
Reactions
 Lowering Energy of Activation (EA)
 Enzymes do not affect the change in free-energy

hasten reactions that would occur eventually
Biological catalysts


Specific for the molecules they catalyze
Activity often enhanced or suppressed by their
reactants or products
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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
Catalysts
 Catalyst -- chemical agent that speeds up a reaction
without being consumed by the reaction
 Enzyme -- catalytic protein
 Example: Hydrolysis of sucrose by sucrase
Sucrose
C12H22O11
Glucose
C6H12O6
Fructose
C6H12O6
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Enzymes
 Enzymes are a type of protein that acts as a catalyst,
speeding up chemical reactions
 Enzymes can
perform their
functions
repeatedly,
functioning as
workhorses that
carry out the
processes of life
Substrate
(sucrose)
Glucose
Fructose
Enzyme
(sucrose)
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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.
Optimal temperature for
typical human enzyme
An enzyme’s
activity can be
affected by:

General
environmental
factors
o
o

temperature
pH
Optimal temperature for
enzyme of thermophilic
(heat-tolerant
bacteria)
LE 8-18
0
40
60
Temperature (°C)
20
80
100
Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach enzyme)
Chemicals that
specifically
influence the
enzyme
0
1
2
3
Optimal pH
for trypsin
(intestinal
enzyme)
4
5
pH
Optimal pH for two enzymes
6
7
8
9
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 Competitive -- bind to
the active site of an
enzyme
 Noncompetitive -- bind
to another part of an
enzyme


A substrate can
bind normally to the
active site of an
LE 8-19
enzyme.
Substrate
Active site
Enzyme
Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
changes shape
makes active site less
effective
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
helps control metabolism
 Chemical chaos -- if cell’s metabolic pathways were
not tightly regulated
 Cells switch genes on or off that encode specific
enzymes
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Allosteric Regulation of Enzymes
Enzymes -- active and inactive forms
 The
binding of activator -- stabilizes the active
form
 The binding of an inhibitor -- stabilizes the inactive
form
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Allosteric activator
stabilizes active form.
LE 8-20a
Allosteric enzyme
with four subunits
Allosteric
regulation
function affected by
binding of a
regulatory molecule
at another site
Regulatory
site (one
of four)
Active site
(one of four)
Activator
Active form
Stabilized active form
Oscillation
Nonfunctional
active site
Inactive form
Allosteric inhibitor
stabilizes inactive form.
Inhibitor
Allosteric activators and inhibitors
Stabilized inactive
form
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Allosteric Regulation
Cooperativity -- can amplify enzyme activity
Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.
Substrate
Inactive form
Cooperativity another type of allosteric activation
Stabilized active form
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Feedback
Inhibition
Isoleucine
used up by
cell
 End product of a
metabolic pathway
shuts down the
pathway
Intermediate A
Feedback
inhibition
Isoleucine
binds to
allosteric
site
Active site of
enzyme 1 can’t
bind
Intermediate B
theonine
pathway off
Intermediate C
Intermediate D
End product
(isoleucine)
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