Energy and Metabolism
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The Energy of Life
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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
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Enzymes Lower the EA Barrier
Course of
reaction
without
enzyme
EA
without
enzyme
Free energy
EA with
enzyme
is lower
Reactants
∆G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
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Enzymes Are Biological Catalysts
that…
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•
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Are proteins that carry out most catalysis in living
organisms.
Are highly specific that can speed up only one or a
few chemical reactions.
Have unique three-dimensional shape that enables
an enzyme to stabilize a temporary association
between substrates.
It is not changed or consumed in the reaction, only
a small amount is needed, and can then be reused.
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 Substate
Active site
Enzyme
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Substrate Specificity of Enzymes
•
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.
Enzyme- substrate
complex
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The Catalytic Cycle Of An Enzyme
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
2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
3 Active site can lower EA
and speed up a reaction by
• acting as a template for
substrate orientation,
• stressing the substrate bonds
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
4 Substrates are converted into Products.
Products
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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
H2O
Active site
Enzyme
4 Products are
released, and the
enzyme is free to
bind other
substrates.
3 The binding of the substrate
and enzyme places stress on
the glucose-fructose bond,
and the bond breaks.
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Factors Affecting Enzyme Activity
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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
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Effects of Temperature and pH
Each enzyme has an optimal temperature in
which it can function
Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
(heat-tolerant)
bacteria
Rate of reaction
•
0
20
40
Temperature (Cº)
(a) Optimal temperature for two enzymes
80
100
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Effects of Temperature and pH
•
Each enzyme has an optimal pH in which
it can function
Optimal pH for pepsin
(stomach enzyme)
Rate of reaction
Optimal pH
for trypsin
(intestinal
enzyme)
3
4
0
2
1
(b) Optimal pH for two enzymes
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7
8
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Figure 8.18
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Factors Affecting Enzyme Activity
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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
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
(a) Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
Competitive
inhibitor
(b) Competitive inhibition
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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
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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
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Regulation Of Enzyme Activity Helps
Control Metabolism
•
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
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The term allostery comes from
the Greek allos, "other", and stereos,
"solid (object)", in reference to the
fact that the regulatory site of an
allosteric protein is physically distinct
from its active site.
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Allosteric Activation and Inhibition
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Most allosterically regulated
enzymes are made from
polypeptide subunits
• Each enzyme has an active and an
inactive form
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Allosteric Activation
The binding of an activator stabilizes the active
form of the enzyme.
Allosteric Inhibition
The binding of an inhibitor stabilizes the inactive
form of the enzyme
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Allosteric activater
stabilizes active from
Allosteric enyzme
with four subunits
Active site
(one of four)
Regulatory
site (one
of four)
Activator
Active form
Stabilized active form
Allosteric activater
stabilizes inactive form
Oscillation
Nonfunctional
active
site
Inactive form
Inhibitor
Stabilized inactive
form
(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors
dissociate when at low concentrations. The enzyme can then oscillate again.
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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
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Regulation of Biochemical Pathways
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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
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Positive Feedback in Coagulation
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In Feedback Inhibition:
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The end product of a
metabolic pathway
shuts down the
pathway
• When the cell
produces increasing
quantities of a
particular product, it
automatically inhibits
its ability to produce
more of the substance
Active site
available
Initial substrate
(threonine)
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 is
switched off
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)
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Harmful Effects of Positive Feedback
Positive feedback can be harmful. Two specific
examples of these harmful outcomes would be:
1. Fever can cause a positive feedback within
homeostasis that pushes the body temperature
continually higher. If the temperature reaches 45
degrees centigrade (113 degrees Fahrenheit) cellular
proteins denature bringing metabolism to a stop and
death.
2. Chronic hypertension can favor the process of
atherosclerosis which causes the openings of blood
vessels to narrow. This, in turn, will intensify the
hypertension and bring on more damage to the walls
of blood vessels.
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http://www.mhhe.com/biosci/esp/2002_gene
ral/Esp/folder_structure/tr/m1/s7/trm1s7_3.ht
m
http://www.hopkinsmedicine.org/hematology/
Coagulation.swf
http://www.youtube.com/watch?v=hb92wr93
JrE
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