TABLE 5.1 Types of inhibition (when catalysis conforms to Michaelis–Menten kinetics)
a.
Reversible
Mode of inhibitor
binding
Kinetic equation
IC
50
versus
K
i
Competitive
Unbound enzyme
V
¼
V
max
=ð
1
þ
K
m
=S
=ð
1
þ
I=
K
ÞÞi
IC
50
¼
K
ði
1
þ
S=
K
m
Þ
Uncompetitive
Substrate-bound enzyme
V
=
V
max
/(1 + I/
K
+i
K
m
/S
)IC
50
=
K
(^) i
(1 +
S/
K
m
)
Noncompetitive
Unbound and bound enzyme
at different site(s) of substrate–enzyme binding site
V
¼
V
max
=ð
1
þ
K
=s
SÞ
=ð
1
þ
I=
K
Þi
IC
50
¼
K
i
Mixed
Unbound and bound enzyme
at the same and different site(s)of substrate–enzyme binding site
V
¼
V
max
=ðð
1
þ
I=
K
0 Þi
þð
1
þ
K
=s
SÞð
1
þ
I=
K
ÞÞi
IC
50
¼
K
ði
1
þ
S=
K
m
Þ=
ð^1
þ
K
=i
K
0 Þði
S=
K
m
ÞÞ
Metabolism-based
IrreversibleMI-complex
kabs
¼
kinact
I=
ðK
þi
IÞ
Time-dependent formation of
potent reversible inhibitor
Abbreviations
:V
, velocity at a given substrate concentration;
Vmax
, maximum velocity;
K
, the binding affinity between substrate and enzyme;m
Ks
, dissociation
constant of substrate–enzyme complex;
K
, dissociation constant of inhibitor–enzyme complex;i
Kobs
, rate of inactivation at a given inhibitor concentration;
kinact
, maximal rate of inactivation;
K
, half maximal rate of inactivation (exact physical meaning is not defined); MI, metabolite–intermediate;I
Ki
0 , dissociation
constant of inhibitor–enzyme complex in the presence of substrate;
S, substrate concentration; IC
50
, concentration of inhibitor that gives rise to a 50% decrease
in activity.aSegel (1993); Silverman (1988); Zhang and Wong, 2005.
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