The interaction between the substrate and the enzyme takes place in a particular region of the enzyme molecule called the active site.
In many instances compounds other than the normal substrate for a particular enzyme-catalyzed reaction may bind to the enzyme’s active site, and this has a significant effect on the kinetics of the normal reaction.
One possible consequence of this phenomenon is the inhibition of normal enzyme activity, and such compounds are therefore called enzyme inhibitors.
(Usually, the inhibitor is unaltered by its interaction with the enzyme.) In some instances, the normal substrate (S) and the inhibitor (T) compete with each other for the active site of the enzyme; the manner in which this affects the normal kinetics of the reaction is shown in Figure 8-8. Vmax is not altered by the presence of a competitive inhibitor, but the KM is elevated.
As can be seen in Figure 8-8, the effect of the inhibitor is maximal at low substrate concentration (i.e., when 1/[S] is large) and minimal at high substrate concentration (i.e., when 1/[S] approaches zero).
A classic example of this form of inhibition is the competition between succinic acid and malonic acid for the enzyme succinic acid dehydrogenase. In this instance, competition between these two compounds for the active site of the enzyme is understandable in view of their marked chemical similarity (Fig. 8-9). Succinic acid is the normal substrate for the enzyme and, in the absence of the inhibitor, is converted to fumaric acid.
Enzyme inhibition can also be noncompetitive in that the binding of the inhibitor to the enzyme cannot be reversed by increasing the concentration of the normal substrate. A common example of negative inhibition is the action of heavy metals such as mercury on the active sites of enzymes containing a reactive sulfhydryl (i.e., -SH) group. In effect, the presence of the inhibitor prevents some percentage of the enzyme present from participating in normal catalysis. As a result, the maximum reaction velocity is depressed, even though the Ku value remains the same (Fig. 8- 10).
The inhibition of enzyme activity by competitors also occurs naturally in cells and serves in the regulation of certain metabolic pathways.