Biomedical Engineering Reference
In-Depth Information
Irreversible inhibitors such as heavy metals (lead, cadium, mercury, and others) form
a stable complex with enzyme and reduce enzyme activity. Such enzyme inhibition may
be reversed only by using chelating agents such as ethylenediaminetetraacetic acid
(EDTA) and citrate. Reversible inhibitors may dissociate more easily from the enzyme after
binding. The three major classes of reversible enzyme inhibitions are competitive, noncom-
petitive, and uncompetitive inhibitions. The substrate may act as an inhibitor in some
cases.
Competitive inhibitors are usually substrate analogs and compete with substrate for the
active site of the enzyme. The competitive enzyme inhibition scheme can be described as
k 1
k 2
E + S
ES
E + P
k -1
+
I
(8.41)
K I
EI
Assuming rapid equilibrium and with the definition of
k 1
k 1 ¼ ½
E
½
S
K m ¼
(8.42)
½
ES
K I ¼ ½
½
E
I
(8.43)
½
EI
½
E
0 ¼½
E
þ½
ES
þ½
EI
(8.44)
and
r p ¼ k 2 ½
ES
(8.45)
we can develop the following equation for the rate of enzymatic conversion:
r max ½
S
r P ¼
K m
(8.46)
½
K I
I
þ½
S
or
K m ; app þ½
r max ½
S
r P ¼
(8.47)
S
where
K m ; app ¼ K m
½
K I
I
(8.48)
The net effect of competitive inhibition is an increased value of K m,app and, therefore, reduced
reaction rate. Competitive inhibition can be overcome by high concentrations of substrate.
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