Enzymes Are Subject to Reversible or Irreversible Inhibition:
Enzymes inhibitors are molecules that interfere with catalysis, slowing or halting
One common type of reversible inhibition is called competitive. A competitive
inhibitor competes with the substrate for the active site of an enzyme. While the
inhibitor (I) occupies the active site, it prevents binding of the substrate to the
enzyme. Many competitive inhibitors are structurally similar to the substrate
and combine with the enzyme to form an EI complex, but without leading to
catalysis. Because the inhibitor binds reversibly to the enzyme, the competition
can be biased to favor the substrate simply by adding more substrate. When [S]
far exceeds [I], the probability that an inhibitor molecule will bind to the enzyme
is minimized and the reaction exhibits a normal Vmax. However, the [S] at which
Vo = 1/2Vmax, the apparent Km, increases in the presence of inhibitor by the
factor of alpha.
Two other types of reversible inhibition, uncompetitive and mixed, can be
defined in terms of one-substrate enzymes, but are in practice observed only
with enzymes having two or more substrates. An uncompetitive inhibitor binds
at a site distinct from the substrate active site and, unlike a competitive inhibitor,
binds only to the ES complex. An uncompetitive inhibitor lowers the measured
Vmax. Apparent Km also decreases, because the [S] required to reach one-half
Vmax decreased by the factor alpha’.
A mixed inhibitor also binds at a site distinct from the substrate active site, but it
binds to either E or ES. A mixed inhibitor usually affects both Km and Vmax.
The irreversible inhibitors bind covalently with or destroy a functional group on
an enzyme that is essential for the enzyme’s activity, or form a particularly stable
Regulatory enzymes exhibit increased or decreased catalytic activity in response
to certain signals. The activities of regulatory enzymes are modulated in a
variety of ways. Allosteric enzymes function through reversible, non-covalent
binding of regulatory compounds called allosteric modulators or allosteric
effectors, which are generally small metabolites or cofactors.