Cambridge International A Level Biology Revision Guide

Chapter 3: Enzymes
Enzyme inhibitors
Competitive, reversible inhibition
As we have seen, the active site of an enzyme fits one
particular substrate perfectly. It is possible, however, for
some other molecule to bind to an enzyme’s active site if
it is very similar in shape to the enzyme’s substrate. This
would then inhibit the enzyme’s function.
If an inhibitor molecule binds only briefly to the site,
there is competition between it and the substrate for the
site. If there is much more of the substrate present than
the inhibitor, substrate molecules can easily bind to the
active site in the usual way, and so the enzyme’s function is
unaffected. However, if the concentration of the inhibitor
rises, or that of the substrate falls, it becomes less and less
likely that the substrate will collide with an empty site.
The enzyme’s function is then inhibited. This is therefore
known as competitive inhibition (Figure 3.12a). It is said
a Competitive inhibition
enzyme
active site
b Non-competitive inhibition
Other molecules may bind
elsewhere on the enzyme,
distorting its active site.
substrate fits
precisely into the
enzyme’s active site
competitive inhibitor
has a similar shape to
the substrate and fits
into the enzyme’s
active site
active site
to be reversible (not permanent) because it can be reversed
by increasing the concentration of the substrate.
An example of competitive inhibition occurs in the
treatment of a person who has drunk ethylene glycol.
Ethylene glycol is used as antifreeze, and is sometimes
drunk accidentally. Ethylene glycol is rapidly converted
in the body to oxalic acid, which can cause irreversible
kidney damage. However, the active site of the enzyme
which converts ethylene glycol to oxalic acid will also
accept ethanol. If the poisoned person is given a large dose
of ethanol, the ethanol acts as a competitive inhibitor,
slowing down the action of the enzyme on ethylene glycol
for long enough to allow the ethylene glycol to be excreted.
Non-competitive, reversible inhibition
A different kind of reversible inhibition takes place if a
molecule can bind to another part of the enzyme rather
than the active site. While the inhibitor is bound to the
enzyme it can seriously disrupt the normal arrangement
of hydrogen bonds and hydrophobic interactions holding
the enzyme molecule in its three-dimensional shape
(Chapter 2). The resulting distortion ripples across the
molecule to the active site, making the enzyme unsuitable
for the substrate. While the inhibitor is attached to the
enzyme, the enzyme’s function is blocked no matter how
much substrate is present, so this is an example of noncompetitive
inhibition (Figure 3.12b).
Inhibition of enzyme function can be lethal, but in
many situations inhibition is essential. For example,
metabolic reactions must be very finely controlled and
balanced, so no single enzyme can be allowed to ‘run
wild’, constantly churning out more and more product.
One way of controlling metabolic reactions is to use the
end-product of a chain of reactions as a non-competitive,
reversible inhibitor (Figure 3.13). As the enzyme converts
substrate to product, it is slowed down because the end-
enzyme 1
enzyme 2
inhibition
enzyme 3
61
non-competitive inhibitor
enzyme
Figure 3.12 Enzyme inhibition. a Competitive inhibition.
b Non-competitive inhibition.
substrate product 1
product 2
product 3
(end-product)
Figure 3.13 End-product inhibition. As levels of product 3 rise,
there is increasing inhibition of enzyme 1. So, less product 1 is
made and hence less product 2 and 3. Falling levels of product
3 allow increased function of enzyme 1 so products 1, 2 and 3
rise again and the cycle continues. This end-product inhibition
finely controls levels of product 3 between narrow upper and
lower limits, and is an example of a feedback mechanism.