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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