Drug Metabolism in Drug Design and Development Basic Concepts and Practice

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4.9 Mechanism-Based Enzyme Inactivation Kinetics


Mechanism-based enzyme inactivation kinetics refers to the irreversible
inhibition of an enzyme via a catalytically formed reactive intermediate that
binds covalently (typically) to the enzyme active site prior to release and causes
permanent inactivation of the enzyme. This type of inhibition is also known as


FIGURE 4.10 Diagnostic plots to determine the type of inhibition occurring in a
kinetic reaction. Left side, panels (a), (b), and (c) are Dixon plots representative
of competitive, mixed, and uncompetitive inhibition, respectively. Right side, panels
(d), (e), and (f) are Cornish-Bowden plots representative of competitive, mixed, and
uncompetitive inhibition, respectively.


108 ENZYME KINETICS

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