Transcript Enzyme Inhibition

Part 2
INHIBITION
ALLOSTERIC REGULATION
FEEDBACK INHIBITION
Remember…
 Enzymes catalyze (speed up) biological reactions
 The substrate (the reactants) must bind to the enzyme at
the active site.
 Enzyme Animations:
 http://highered.mcgraw

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
hill.com/sites/0072495855/student_view0/chapter2/animation__how_enzymes_wo
rk.html
http://www.youtube.com/watch?v=TLr7_2wnIXU
http://www.youtube.com/watch?v=z8lG8X9ZvxQ&feature=related
http://www.youtube.com/watch?v=CZD5xsOKres&feature=related
http://www.youtube.com/watch?v=XTUm-75-PL4
Remember….
 Enzymes are NOT reactants or products
 Enzymes are NOT used up in a reaction
 Enzymes may be used again over and over again (so
long has they have not been denatured)
 Enzymes are specific to a particular substrate (or group
of substrates)
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1)
Cells must control enzyme activity to coordinate
cellular activities
This can be done by:
Restricting the production of a particular enzyme
(enzymes are proteins, so your body can control how
much you make of them)
1)
Inhibiting the action of an enzyme
This may involve
a) competitive inhibition
b) noncompetitive inhibition
- including allosteric regulation
c) feedback inhibition
ENZYME INHBITION
 Sometimes enzyme function can be inhibited by other
molecules (reducing the rate of enzyme-controlled
reactions)
 These molecules are called INHIBITORS
 There are COMPETITIVE INHIBITORS and NON-
COMPETITIVE INHIBITORS
a) Competitive Inhibitors
 These are molecules that are similar in shape to the
substrate
 They bind to the enzyme’s active site preventing the
real substrate from binding
 The molecule “competes” with the substrate for the
active site
 This can be overcome by increasing the substrate
concentration
Competitive
Inhibitor
Now the substrate cannot
get to the active site
because it is blocked by
the inhibitor.
enzyme
substrate
Ex: PRONTOSIL (competitive inhibitor)
 PRONTOSIL – is an antibacterial drug
 Bacteria require folic acid for replication of genetic material
 Prontosil binds to the enzyme that makes folic acid preventing
other substrates from binding
 As a result, folic acid is not longer made and the bacterial cell dies
 Since animal cells don’t make folic acid themselves, they do not
have this enzyme and so Prontosil has no effect on them
b) Noncompetitive Inhibition
 A molecule binds to the enzyme at a location other
than the active site
 This binding alters the shape of the enzyme, changing
the shape of the active site
 The enzyme is now dysfunctional because the
substrate now cannot bind to the active site.
 Adding more substrate will not affect the reaction
because the active site is unavailable.
Non competitive
inhibitor
substrate
The shape of the
active site has
changed
Therefore, the
substrate no
longer fits in
enzyme
Ex: Cytochrome C Oxidase
(noncompetitive inhibition)
Regular Function
 Speeds up the reduction of oxygen to water in cellular
respiration
 Without it, the reaction will not occur fast enough and
the organism will die because not enough energy is
released.
Ex: Cytochrome C Oxidase
(noncompetitive inhibition)
Inhibition
 CN- attach to the –SH groups in the enzyme
 This destroys the disulfide bridges and thus
changing the tertiary structure of the enzyme
 Change in the shape results in the change in the
active site thus the substrate cannot bind and
cytochrome c oxidase is nonfuctional.
Animations
 http://www.youtube.com/watch?v=PILzvT3spCQ
Allosteric Regulation
 Some enzymes have receptor sites away from the active
site called ALLOSTERIC SITES
 (These enzymes are usually proteins made of several
subunits each with an active site)
 Substance that bind to the allosteric sites may inhibit
or stimulate (increase) the enzyme activity.
Allosteric Regulation - Activators
 Binding an ACTIVATOR to an allosteric site
stabilizes the protein conformation
 This keeps all the active sites available for the
substrates to bind to them.
Allosteric Inhibition
 Binding of an allosteric inhibitor (a type of
noncompetitive inhibitor) stabilizes the
inactive form of the enzyme
Allosteric Regulation
 The binding of an activator or an inhibitor affects the
activity of all the active sites on the enzyme
 Animation: “ An example of allosteric activation of an
enzyme” (Text video)
c) Feedback Inhibition
 Method of controlling metabolic pathways
 Negative feedback inhibition is like a thermostat.
 When it is cold, the thermostat turns on the heater to
produce heat.
 When it is too warm, the heat will cause the
thermostat to turn off the heater
Feedback Inhibition
Cold
Thermostat
Heater
Heat
INHIBITS
 Heat has a negative effect on the thermostat;
 A build up of product inhibits the enzymes and the
reaction
Feedback Inhibition
 Many enzymatic pathways are regulated by feedback
inhibition
 As the enzyme’s end product accumulates, it inhibits
the enzyme by binding to the first enzyme in the
pathway.
 This shuts down the entire sequence.
Feedback Inhibition
 As the product is used up over time, the concentration
of product decreases
 The inhibition product will detach from the enzyme
allowing it to become active once again and produce
product.
 When the product concentration gets too high again,
the product will once again allosterically inhibit the
enzyme
Animations
 Feedback inhibition animation (text)
 http://highered.mcgraw-
hill.com/sites/0072507470/student_view0/chapter2/a
nimation__feedback_inhibition_of_biochemical_path
ways.html