Enzyme

Inhibitors
 Enzyme Inhibitors
Introduction

• Many substances alter the activity of an

enzyme by combining with it in a way
that influences the binding of substrate
and/or its turnover number.
• Substances that reduce an enzyme’s
activity in this way are known as
inhibitors.

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 Enzyme Inhibitors
Re ve rs i b l e Vs I r re ve rs i b l e I n h i b i to rs

• Irreversible enzyme inhibitors, or inactivators, bind to

the enzyme so tightly that they permanently block
the enzyme’s activity. For example reagents that
chemically modify specific amino acid residues can
act as inactivators.
• Reversible enzyme inhibitors diminish an enzyme’s
activity by interacting reversibly with it. Some
enzyme inhibitors are substances that structurally
resemble their enzyme’s substrates but either do not
react or react very slowly.

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Enzyme Inhibitors
Ty p e s o f I n h i b i t o r s

• A substance that competes directly with a normal

substrate for an enzyme’s substrate-binding site is
known as a competitive inhibitor.

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Enzyme Inhibitors
Ty p e s o f I n h i b i t o r s

• A substance that binds directly to the enzyme-

substrate complex but not to the free enzyme is
known as an uncompetitive inhibitor.

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Enzyme Inhibitors
Ty p e s o f I n h i b i t o r s

• A substance that interacts with the enzyme in a way

that affects substrate binding as well as catalytic
activity is known as a mixed inhibitor
(noncompetitive inhibitor).

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 Enzyme Inhibition
The Effect on Michaelis -Menten Equation

• The Michaelis–Menten equation describes the

rate of the enzymatic reaction as a function of
substrate concentration represented by the
equation:

where v0 is the initial velocity of the reaction, Vmax is the

maximal velocity of a reaction that occurs at high substrate
concentrations, KM is the Michaelis constant, and [S] is the
concentration of the substrate.

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 Enzyme Inhibition
The Effect on Michaelis -Menten Equation

• Adding inhibitors to the enzymatic reaction can

affect the values of the maximal velocity VMAX,
and the Michaelis constant KM.
• These changes vary depending on the type of the
inhibitors used.

Let’s elaborate on the types of inhibition, how they

react, and how they affect the maximal velocity
and Michaelis constant on the next slides.

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Competitive Inhibition But how does competitive inhibition affect the
The general model for competitive inhibition Michaelis-Menten equation?
is given by the following reaction scheme:

Here, I is the inhibitor, EI is the catalytically inactive

enzyme–inhibitor complex, and it is assumed that the
inhibitor binds reversibly to the enzyme and is in rapid
equilibrium with it so that

Therefore, KM increases when competitive

inhibitor is present.
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Uncompetitive Inhibition But how does uncompetitive inhibition affect the
The general model for uncompetitive inhibition
is given by the following reaction scheme: Michaelis-Menten equation?

The binding of uncompetitive inhibitor, which need not VMAX

resemble substrate, presumably distorts the active site,
thereby rendering the enzyme catalytically inactive.

Therefore, both VMAX and KM decreases when

uncompetitive inhibitor is present.
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Noncompetitive Inhibition FR
The general model for noncompetitive inhibition But how does noncompetitive inhibition affect the
is given by the following reaction scheme: Michaelis-Menten equation?

Presumably, a mixed inhibitor binds to enzyme sites

that participate in both substrate binding and
catalysis.

Therefore, VMAX decreases when noncompetitive inhibitor is

present. KM may increase or decrease depending on the
relative values of α and α’
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Inhibition Types FR
SUMMARY

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Sample Problem
For an enzyme-catalyzed reaction, the presence of 5 nM of a
reversible inhibitor yields a Vmax value that is 80% of the value in the
absence of the inhibitor. The KM value is unchanged. (a) What type of
inhibition is likely occurring? (b) What proportion of the enzyme
molecules have bound inhibitor? (c) Calculate the inhibition
constant.
Thank you for listening! 