Transcript 8.1 Metabolism

Essential Idea
• Metabolic reactions are regulated in response
to the cell’s needs.
Understandingis
• Metabolic pathways consist of chains and
cycles of enzyme-catalysed reactions.
• Enzymes lower the activation energy of the
chemical reactions that they catalyse.
• Enzyme inhibitors can be competitive or noncompetitive.
• Metabolic pathways can be controlled by endproduct inhibition.
Skills & Application
• Application: End-product inhibition of the
pathway that converts threonine to isoleucine.
• Application: Use of databases to identify
potential new anti-malarial drugs.
• Skill: Calculating and plotting rates of reaction
from raw experimental results.
• Skill: Distinguishing different types of inhibition
from graphs at specified substrate
concentration.
Guidance
• Enzyme inhibition should be studied using one
specific example for competitive and noncompetitive inhibition.
IB Assessment Statement
• State that metabolic pathways consist of chains
and cycles of enzyme catalyzed reactions.
State that metabolic pathways consist of chains and
cycles of enzyme catalyzed reactions.
7.6.1 Metabolic pathways.
• Chemical changes in living things often
occurring with a number of intermediate
stages.
• Each stage has its own enzyme.
• Catabolic pathways breakdown molecules
• Anabolic pathways build up molecules
State that metabolic pathways consist of chains and
cycles of enzyme catalyzed reactions.
7.6.1 Metabolic pathways Animation --Click here for Animation: http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter2/animation
__a_biochemical_pathway.html
State that metabolic pathways consist of chains and
cycles of enzyme catalyzed reactions.
Two Types Metabolic pathways.
• Linear Pathway
• Cyclical pathway
Linear metabolic pathways.
• Enzyme (1) is specific to substrate
1. This is changed to product 1.
• Enzyme (2) is specific to product1
which becomes the substrate and
converted to product 2.
• Enzyme (3) is specific to products
which becomes the substrate and
converted t o product 3.
• Product 3 is called the 'End
product'.
Cyclic metabolic pathways.
•
The initial substrate is fed into the cycle.
•
Enzyme (1) combines the regenerated
'intermediate 4' with the initial substrate to
catalyses the production of intermediate 1.
•
Enzyme (2) is specific to intermediate 1 and
converts intermediate 1 to intermediate 2
•
Enzyme (3) is specific to intermediate 2 and
catalyses it conversion to product and
intermediate 3.
•
Enzyme (4) is specific to intermediate 3 and
catalyses its conversion to intermediate 4.
•
The difference is the regeneration of the
intermediate, in this case intermediate 4.
IB Assessment statement
Describe the induced-fit model.
• This is an extension of the lock-and-key model.
• Its importance in accounting for the ability of some
enzymes to bind to several substrates should be
mentioned.
Induced fit model
• Induced fit model - A model for enzymesubstrate interaction
• states only the correct substrate is capable of
inducing the correct shape of the active site
• This change in shape allows the enzyme to
perform its catalytic function.
•
Induced Fit Animation Click here:
http://www.stolaf.edu/people/giannini/flashanimat/enzymes/enzyme.swf
Induced fit model
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.
IB Assessment Statement
Explain that enzymes lower the
activation energy of the chemical
reactions that they catalyse.
– Only exothermic reactions should be
considered. Specific energy values do
not need to be recalled.
Exergonic and Endergonic Reactions in Metabolism
• An exergonic reaction proceeds with a net
release of energy
• An endergonic reaction absorbs energy from
its surroundings
Exothermic Reaction
Free energy
Reactants
Amount of
energy
released
(G < 0)
Energy
Products
Progress of the reaction
Exergonic reaction: energy released
LE 8-6b
Endogonic Reaction
Free energy
Products
Energy
Reactants
Progress of the reaction
Endergonic reaction: energy required
Amount of
energy
required
(G > 0)
Effect of Catalyst on Activation Energy
Enzymes lower the activation energy of the
chemical reaction that they catalyze.
•
In the activated complex or transition
state energy is put into the substrate to
weaken the structure. This allow the
reaction to occur with a minimal amount
of additional energy required.
•
Normal activation energy would cause
damage to the proteins of the cell. Thus
reduced activation energy make these
reactions possible in a cell.
•
After the product is formed energy is
released.
•
Exergonic reactions release more energy
than the activation energy. .
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
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
IB Assessment Statement
• Explain the difference between competitive and
non-competitive inhibition, with reference to
one example of each.
Enzyme Inhibitors
• Competitive inhibitors bind to the active site of
an enzyme, competing with the substrate
• Noncompetitive inhibitors bind to another part of
an enzyme, causing the enzyme to change
shape and making the active site less effective
The inhibitor has
a similar shape
to the usual
substrate for the
enzyme, and
competes with it
for the active site
The activity of
the enzyme is
inhibited till the
inhibitor has a
dissociated.
Non-competitive inhibition
• Substrates and inhibitors do not have a
similar structure.
• Inhibitors bind at a different site from the
active site
• Inhibitors hence change the conformation of
the enzyme.
• Substrate may/may not bind
• Active site doesn’t catalyze the reaction
Non-competitive inhibition
Non-competitive inhibition
A substrate can
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
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
Allosteric Regulation of Enzymes
• Allosteric regulation is the term used to describe
cases where a enzyme’s function at one site is
affected by binding of a regulatory molecule at
another site
• Allosteric regulation may either inhibit or
stimulate an enzyme’s activity
Allosteric Activation and Inhibition
• Each enzyme has active and inactive forms
• The binding of an activator stabilizes the active
form of the enzyme
• The binding of an inhibitor stabilizes the inactive
form of the enzyme
LE 8-20a
Allosteric enzyme
with four subunits
Regulatory
site (one
of four)
Active site
(one of four)
Activator
Active form
Oscillation
Nonfunctional
active site
Allosteric activator
stabilizes active form.
Inactive form
Stabilized active form
Allosteric inhibitor
stabilizes inactive form.
Inhibitor
Allosteric activators and inhibitors
Stabilized inactive
form
LE 8-20b
Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.
Substrate
Inactive form
Stabilized active form
Cooperativity another type of allosteric activation
IB Assessment Statement
• Explain the control of metabolic pathways by
end-product inhibition, including the role of
allosteric sites
Feedback Inhibition
• In feedback inhibition, the end product of a
metabolic pathway shuts down the pathway
• Feedback inhibition prevents a cell from wasting
chemical resources by synthesizing more
product than is needed
•
Click here for Animation: http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter2/animation__fee
dback_inhibition_of_biochemical_pathways.html
Feedback Inhibition
Initial substrate
(threonine)
Active site
available
Isoleucine
used up by
cell
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Intermediate A
Feedback
Enzyme 2
inhibition Active site of
enzyme 1 can’t
bind
Intermediate B
theonine
pathway off
Enzyme 3
Isoleucine
binds to
allosteric
site
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)
Feedback Inhibition a detailed example
1. Isoleucine the end product, this molecule can
inhibit the enzyme Threonine Deaminase
2. The inhibition occurs at an inhibition site on
the enzyme but not the active site
3. An excess of end product (Isoleucine)
switches off any more production of that
product, isoleucine.
4. At high concentrations, Isoleucine attaches
to the inhibition site of Threonine deaminase.
5. This attachment causes the active site of the
enzyme to change blocking any further
reaction.
6. Isoleucine is used up in cellular processes
that require this particular amino acid.
Feedback Inhibition a detailed example
7. The isoleucine concentration in the cell falls and so
the Isoleucine that is attached to the enzyme
detaches. This amino acid is also used up in the
various cellular processes.
8. With the inhibitor removed the the active site then
becomes active again and the pathway switches
back on.
9. The isoleucine is again in production but once high
concentrations are reached the pathways is once
more inhibited. The process then cycles on in
alternating stages of production and inhibition
10. Notice the similarity with non-competitive inhibition.
11. This mechanism makes the pathway self-regulating
in terms of product manufacture.