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Chapter 8
150-157
If all Exergonic
Reactions happen
spontaneously…
…then how come all
of them haven’t
already happened?
Activation Energy!
We need catalysts!
Biological Catalysts
Are Enzymes
Activation Energy
C6H12O6 +O2
Activation
Energy
Energy
CO2 + H20
Reaction Time
Enzymes are Proteins
• Organic catalysts - increase the
rate of chemical reactions in cells.
• Hold reactant molecules close
together for reaction to occur- uses
an active site.
• The active site is used to bind the
reactant molecules-substrate.
The active site:
–Is the region on the enzyme
where the substrate binds.
Substate
Active site
Enzyme
Figure 8.16
(a)
• Induced fit of a substrate:
– Brings chemical groups of the active site
into positions that enhance their ability to
catalyze the chemical reaction
Enzyme- substrate
complex
Figure 8.16
(b)
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
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,
• stressing the substrates
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
4 Substrates are
Converted into
Products.
Conditions that Affect Protein Shape
Can disrupt H bonds by:
• High Temperature
• pH Changes (Acidic or Basic)
• Salt (or Ion) Concentration
• Binding of Regulatory Molecules
Disrupting the 2°, 3°, 4° structure is
called denaturation.
Enzymes
• Enzymes have a temperature
optimum.
• Too Cold - H bonds and van der Waals
forces aren’t flexible enough to allow the
induced fit for catalysis.
• Too Hot - they are too weak to maintain
the enzymes shape and break apart.
Rate of Reaction
Most Human Enzyme Temp. Optimums
Male Reprod.
Enzymes
31
33
35
37
39
41
Rxn Temperature, °C
43
Siamese Cats and Pigment
Enzymes
3 wks
old
4 yrs.
old
Pigment Enzymes in Harp
Seal Pups
Rate of Reaction
Most Human Enzyme pH Optimums
Pepsin
2
3
Trypsin
4
5
6
Rxn pH
7
8
Inhibitors and Activators
• Inhibitors – are molecules (usually
proteins) that bind to an enzyme and
decrease its activity.
• Two Kinds:
–A. Competitive Inhibitors – compete
for the same active site as the substrate;
displaces some of the substrate.
–B. Noncompetitive Inhibitors – bind to
the enzyme in some other location other
than its active site., changing its shape.
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.
Figure 8.19
Competitive
inhibitor
(b) Competitive inhibition
Competitive Inhibition
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
Noncompetitive Inhibitors
• These inhibitors bind to a site other
than the active site called the allosteric
site (“other form”).
• Chemical “on/off” switches.
• Called Allosteric Inhibitor.
• If a molecule binds to an allosteric site
and keeps the enzyme in its active
shape – Allosteric Activator.
Enzymes change shape when regulatory
molecules bind to specific sites,
affecting function
Allosteric enyzme
with four subunits
Active site
(one of four)
Regulatory
site (one
of four)
Activator
Active form
Stabilized active form
Allosteric activater
stabilizes active form
Oscillation
Nonfunctional
active
site
Figure 8.20
Allosteric activater
stabilizes active from
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.
Another Look at
Allosteric Inhibitors
Allosteric Activation
Things that help Enyzmes
• Molecules that bind to the active site and HELP
the enzyme’s function – Cofactor.
• Often metal ions, vitamins, etc.
• If cofactor is a nonprotein organic moleculeCoenzyme.
• Coenzymes often serve as electron acceptors
to help break bonds.
• Coenzymes then transfer the electrons to
other compounds. (Remember NAD+ and
FAD+?
Enzymes Work with Co-Enzymes
Captures H+
An Example of a
Biochemical Pathway
Feedback Inhibition
E1
Substrate A
E2
Substrate B
Substrate C
E2
E1
Allosteric Inhibitor
Feedback inhibition
Initial substrate
(threonine)
Active site
available
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition
Isoleucine
binds to
allosteric
site
Active site of
enzyme 1 no
longer binds
threonine;
pathway is
switched off
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
Figure 8.21
End product
(isoleucine)