Non competitive Inhibitors:
A noncompetitive inhibitor is a substance that
interacts with the enyzme, but usually not at the active site.
The noncompetitive inhibitor reacts either remote from or
very close to the active site. The net effect of a non
competitive inhibitor is to change the shape of the enzyme and thus the
active site, so that the substrate can no longer interact with the
enzyme to give a reaction. Non competitive inhibitors are usually
reversible, but are not influenced by concentrations of the substrate
as is the case for a reversible competive inhibitor. See the
graphic on the left.
Inhibitors form strong covalent bonds with an enzyme.
These inhibitors may act at, near, or remote from the active
site. Consequently, they may not be displaced by the addition
of excess substrate. In any case, the basic structure of the
enzyme is modified to the degree that it ceases to work.
Since many enzymes contain sulfhydral (-SH),
alcohol, or acid groups as part of their active sites, any chemical
which can react with them acts as an irreversible inhibitor. Heavy
metals such as Ag+, Hg2+,
Pb2+ have strong affinities for -SH groups.
Nerve gases such as diisopropylfluorophosphate
(DFP) inhibit the active site of acetylcholine esterase by reacting
with the hydroxyl group of serine to make an ester.
Oxalic and citric acid inhibit blood clotting by
forming complexes with calcium ions necessary for the enzyme metal ion
QUES. Explain a method that could be used to
experimentally test whether an inhibitor was competitive or
noncompetitive. Hint: Consider concentration effects.
Example: Chymotrpsin is an
enzyme which hydrolyzes peptides at the carbonyl side of tyr or phe or
trp (i.e. those that have an aromatic side chain. In the graphic on the
left, the substrate and the irreversible inhibitor are shown in the
active site pocket. In the case of the inhibitor the reaction starts in
the same way as with the substrate, but the end result is that the
inhibitor is covalently bonded to the histidine-57 in the active site
and is not reversible.
Chymotrypsin with substrate - Chime
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Chymotrypsin with inhibitor - Chime
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