Re: noncompetitive vs. allosteric inhibition: noncompetitive
inhibitors bind to a site other than the active site and render the enzyme ineffective.
Allosteric inhibitors do the same thing. So, how are they different? And, in what way can
we apply the Michaelis-Menton equation to our understanding of allosteric inhibitors? For
instance, can we quantify what happens with the presence of an allosteric inhibitor, or do
we just have a qualitative understanding?
I agree that at a simple mechanistic level non-competitive and allosteric
inhibition appear the same. There are several differences, however. Allosteric inhibition
generally acts by switching the enzyme between two alternative states, an active form and
an inactive form. It usually works by binding to a sites in a specialized subunit of a
mutimeric protein, and thus binds at several sites. The more inhibitor that binds, the
more then can bind, and vice versa with substrate. The kinetics are thus complicated,
being cooperative, and non-Michaelis Menton, and are beyond the scope of this course. So a
qualitative understanding is all that is called for here. Allosteric inhibition is
designed into the proteins and represents an important physiological process.
Noncompetitive inhibiton is more of a catch-all for non-physiological inhibition that does
not compete with substrate for substrate binding to enzyme. In that, it is defined (and
named) from a negative point of view. As described in your texts, a non-competive
inhibitor may bind to a non-substrate site on a protein and distort it to the point of
non-functionality, and adding more substrate will not alleviate this inhibition. Or, as in
the example I used in lecture, it may simply block a catalytic site without interfering
with substrate binding, an example that is more distinct from allosteric inhibition.