Download The Energy of Life The living cell Is a miniature factory where

10/27/2009
An Introduction to Enzymes and
Metabolism.
Modified from Campbell
„ Overview: The Energy of Life
„ The living cell
„
„
Is a miniature factory where thousands of
reactions occur
Converts energy in many ways
„ Metabolism
„
„
Is the totality of an organism’s chemical
reactions
Arises from interactions between molecules
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Organization of the Chemistry of
Life into Metabolic Pathways
„ A metabolic pathway has many steps
„
„
That begin with a specific molecule and end
with a product
That are each catalyzed by a specific enzyme
Enzyme 1
A
Enzyme 2
Enzyme 3
D
C
B
Reaction 1
Reaction 2
Starting
molecule
Reaction 3
Product
„ Catabolic pathways
„
„
Break down complex molecules into simpler
compounds
Release energy
„ Anabolic pathways
„
„
Build complicated molecules from simpler
ones
Consume energy
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Forms of Energy
„ Energy
„
„
Is the capacity to cause change
Exists in various forms, of which some can
perform work
The First Law of Thermodynamics
„ According to the first law of thermodynamics
„
„
Energy can be transferred and transformed
Energy cannot be created or destroyed
Exergonic and Endergonic
Reactions in Metabolism
„ An exergonic reaction
„
Proceeds with a net release of free energy
and is spontaneous
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Reactants
Free enerrgy
Amount of
energy
released
(∆G <0)
Energy
Products
Progress of the reaction
(a) Exergonic reaction: energy released
Figure 8.6
„ An endergonic reaction
„
Is one that absorbs free energy from its surroundings
and is nonspontaneous
Free energy
y
Products
Amount of
energy
released
l
d
(∆G>0)
Energy
Reactants
Progress of the reaction
(b) Endergonic reaction: energy required
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Equilibrium and Metabolism
„ Reactions in a closed system
„
Eventually reach equilibrium
„ Cells in our body
„
Experience a constant flow of materials in and
out, preventing metabolic pathways from
reaching equilibrium
∆G < 0
(b) An open hydroelectric
system. Flowing water
keeps driving the generator
because intake and outflow
of water keep the system
from reaching equlibrium.
Figure 8.7
„ An analogy for cellular respiration
∆G < 0
∆G < 0
∆G < 0
Figure 8.7
(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 becomes the reactant for the next, so no reaction
reaches equilibrium.
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„ ATP powers cellular work by coupling exergonic
reactions to endergonic reactions
„ 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
The Structure and Hydrolysis of
ATP
„ ATP (adenosine triphosphate)
„
„
Is the cell’s energy shuttle
Provides energy for cellular functions
Adenine
N
O
O
-O
-
-
O
Phosphate groups
Figure 8.8
O
O
C
N
HC
O
O
O
O
NH2
C
N
CH2
-
O
H
H
OH
OH
H
H
CH
C
N
Ribose
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„ Energy is released from ATP
„
When the terminal phosphate bond is broken
P
P
P
Adenosine triphosphate (ATP)
H2 O
P
Figure 8.9
+
i
P
Energy
P
Adenosine diphosphate (ADP)
Inorganic phosphate
How ATP Performs Work
„ ATP drives endergonic reactions
„
By phosphorylation, transferring a phosphate
to other molecules
„ The three types
yp of cellular work
„
Are powered by the hydrolysis of ATP
P
P
i
Motor protein
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
ATP
P
P
Solute
P
i
i
Solute transported
(b) Transport work: ATP phosphorylates transport proteins
P
Glu + NH3
Reactants: Glutamic acid
and ammonia
Figure 8.11
NH2
Glu
+
P
i
Product (glutamine)
made
(c) Chemical work: ATP phosphorylates key reactants
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The Regeneration of ATP
„ Catabolic pathways
„
Drive the regeneration of ATP from ADP and
phosphate
ATP hydrolysis to
ADP + P i yields energy
ATP synthesis from
ADP + P i requires energy
ATP
Energy from catabolism
(exergonic, energy yielding
processes)
Energy for cellular work
(endergonic, energyconsuming processes)
ADP + P
Figure 8.12
i
„ Concept 8.4: Enzymes speed up metabolic
reactions by lowering energy barriers
„ A catalyst
„
Is a chemical agent
g
that speeds
p
up
p a reaction
without being consumed by the reaction
„ An enzyme
„
Is a catalytic protein
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The Activation Barrier
„ Every chemical reaction between molecules
„ Involves both bond breaking and bond forming
„ Hydrolysis
„ Is an example of a chemical reaction
H
CH2OH
CH2OH
O H
O
H
H
H HO
OH
+
O
CH2OH
H
Sucrase
H2O
H
HO
H
OH H
OH
CH2OH
O H
H
OH H
OH
CH2OH
O
HO
OH
H HO
H
CH2OH
OH H
Sucrose
Glucose
Fructose
C12H22O11
C6H12O6
C6H12O6
Figure 8.13
„ The activation energy, EA
„
„
Is the initial amount of energy needed to start
a chemical reaction
Is often supplied in the form of heat from the
surroundings in a system
„ The energy profile for an exergonic reaction
A
B
C
D
Free energy
Transition state
A
B
C
D
EA
Reactants
A
B
C
D
∆G < O
Products
Progress of the reaction
Figure 8.14
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How Enzymes Lower the EA
Barrier
„ An enzyme catalyzes reactions
„
By lowering the EA barrier
Free energ
gy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
∆G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
Figure 8.15
Substrate Specificity of Enzymes
„ The substrate
„
Is the reactant an enzyme acts on
„ The enzyme
„
Binds to its substrate
substrate, forming an enzymeenzyme
substrate complex
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„ The active site
„
Is the region on the 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 chemical reaction
Catalysis in the Enzyme’s Active
Site
„ In an enzymatic reaction
„
The substrate binds to the active site
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1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates
Enzyme-substrate
complex
6 Active site
Is available for
two new substrate
Mole.
Enzyme
5 Products are
Released.
Figure 8.17
Products
2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
3 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,
t
i the
th substrates
b t t
• stressing
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
4 Substrates are
Converted into
Products.
„ The active site can lower an EA barrier by
„
„
„
„
Orienting substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Covalently bonding to the substrate
Effects of Temperature and pH
„ Each enzyme
„
Has an optimal temperature in which it can
function
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„
Has an optimal pH in which it can function
Optimal pH for pepsin
(stomach enzyme)
Rate of rea
action
Optimal pH
for trypsin
(intestinal
enzyme)
3
4
2
1
(b) Optimal pH for two enzymes
0
5
6
7
8
9
Figure 8.18
Cofactors
„ Cofactors
„
Are nonprotein enzyme helpers
„ Coenzymes
„
Are organic cofactors
Enzyme Inhibitors
„ Competitive inhibitors
„
Bind to the active site of an enzyme, competing with
the substrate
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„ 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
Figure 8.19
(c) Noncompetitive inhibition
„ Regulation of enzyme activity helps control
metabolism
„ A cell’s metabolic pathways
„
Must be tightly
g y regulated
g
Allosteric Regulation of 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
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„
They change shape when regulatory molecules bind
to specific sites, affecting function
Allosteric activater
Allosteric enyzme Active site stabilizes active from
with four subunits (one of four)
Regulatory
site (one
of four)
Activator
Active form
Stabilized active form
Allosteric activater
stabilizes active form
Oscillation
NonInhibitor
functionalInactive form
Figure 8.20
Stabilized inactive
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.
Feedback Inhibition
„ In feedback inhibition
„
The end product of a metabolic pathway shuts
down the pathway
Initial substrate
(threonine)
Active site
available
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition
Active site of
enzyme 1 no
longer binds
threonine;
pathway
p
y is
switched off
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
Figure 8.21
End product
(isoleucine)
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