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Example of Competitive Inhibition
Example 1: Malonate competive inhibitor of
succinate dehydrogenase enzyme
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Examples2: Competitive Inhibition-Sulpha drugs
Sulfonamides, as antimetabolites, compete
with para-aminobenzoic acid (PABA) for
incorporation into folic acid.
The action of sulfonamides illustrates the
principle of selective toxicity where some
difference between mammal cells andbacterial cells is exploited.
All cells require folic acid for growth. Folic
acid (as a vitamin is in food) diffuses or is
transported into human cells. However, folic
acid cannot cross bacterial cell walls by
diffusion or active transport. For this reasonbacteria must synthesize folic acid from p-
aminobenzoic acid.
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Competitive Inhibition
DHPS
DHPS
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Uncompetitive Inhibition
Def: Degree of inhibition (i) increases as substrate conc. is increased
In uncompetitive inhibition, inhibitor binds to [ES] rather than free enzyme
scheme
Conformational change: Substrate binding causes conformational change
that expose hidden site for inhibitor binding
The inhibitor affects catalytic function of the enzyme but not the
substrate binding: It appears that substrate binding is favoured in the presence ofcompetitive inhibitor. The removal of ES from equilibria favours more substrate binding
Effect of inhibition can not be overcome by increasing
substrate concentration
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Uncompetitive Inhibition
Graph
Consequences of lowered Km
1. Saturation occurs at lower substrateconcentration
2. Vm/Km is unaffected
3. Velocity at low substrate conc is unaffected
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Uncompetitive Inhibition
L.B. Plot
Secondary Plots
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Classical Non-competitive Inhibition
Degree of Inhibition (i)
-Degree of inhibition is unaffected by substrate concentration. In other
words, fractional inhibition is identical at all concentration, i.e. inhibition is
found at both lower as well as higher substrate concentration
No effect on substrate binding
-A classical non competitive inhibitor has no effect
on substrate binding.
Binding site for inhibitor is other than substratebinding site
-this inhibition is called non-competitive because inhibitor
binding is not at the active site like competitive inhibitor. So to
differentiate this, term non-competitive inhibition is given
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Scheme for classical or pure noncompetitive inhibition
Kinetic equation
Effect on Kinetic parameters
Km is unalteredVm is decreased
Calculation of Km, Vm and Ki
-L.B. Plot
-Secondary plot