08 September 2010
(P. J. Hollenbeck)
Reading: pp. 101-03; 150-152
Problem assignment: 21-23; exam I‘09, #4b-c; exam I ‘06, #5b
ENZYME INHIBITION AND ALLOSTERY
<Substances that inhibit enzymes (inhibitors, “I”) can be classified as reversible or irreversible.
Irreversible inhibitors bind the enzyme permanently - usually covalently - and disrupt the ability of the
active site to bind S, catalyze the reaction, or release products.
Reversible inhibitors bind the enzyme
non-covalently and can dissociate.
Today we will consider the kinetics of reversible inhibition.>
Inhibition of Michaelis enzymes
(see plots below)
(1) Recall from lecture 6,
are so named because they compete
with S for access to the active site.
Their molecular structure resembles that of S.
(2) The degree of inhibition depends on two things: the affinity of inhibitor (I) for the
E’s active site; and the [S] (at fixed [I]), or ratio of [S] to [I].
(3) In the presence of a competitive I, an E can approach its normal V
, but only at
much higher [S] (and [S]/[I]).
As [S] approaches
, it swamps out the access of the I to
the active site, so the active site will always be occupied by S.
Thus, the E can
approach its V
. In the presence of a competitive I, the E also requires a higher [S] to
than it would without I.
Thus, in the presence of competitive I, V
remains the SAME but the K INCREASES.
(1) Non-competitive inhibitors, as their name implies, do not compete with S for the
Instead, they bind to the E at a different site, and their binding has no effect
on the binding of [S] to the active site, only on catalysis.
Thus, their inhibition cannot
be reversed by increasing the [S].
(2) For a particular non-competitive I, the degree of inhibition depends only on [I],
NOT on [S].
Thus, some fraction of the E molecules will be inhibited at any [S].