Explain the competitive enxyme inhinition mechanism with example
Answers
Competitive inhibitors compete for the substrate-binding site of the enzyme with the substrate, because the substrate and the inhibitor bind to identical or overlapping sites. Due to the overlapping nature of the binding sites, a ternary complex—in which the substrate and the inhibitor would simultaneously bind to the enzyme—cannot form. Accordingly, in the enzyme-inhibitor complex, the enzyme is completely inactive.
By popular—but quite misleading—terminology, these inhibitors are said to “displace” the substrate from the enzyme. While this term is aimed to be expressive, it is totally inadequate to explain the mechanism of this type of inhibition. The popular term suggests that the inhibitor would bind to the ES complex and would thus somehow actively force the substrate to dissociate. As already mentioned, no ternary complex is formed—not even temporarily. This inhibitory mechanism simply obeys a thermodynamic principle: two equilibria exist in parallel, one between the enzyme and the inhibitor and another between the enzyme and the substrate. More precisely, the latter one is a quasi-equilibrium because, during the measurement, the enzyme and the substrate are in a steady-state (as shown in Figure 9.4). The equilibrium concentrations of the free compounds and those of the complexes are dictated by the total concentrations of the individual compounds and the affinity of their interactions.
The equilibrium between the enzyme and the inhibitor is described by Equation 9.53 in which the KI term represents a dissociation constant:
The two equilibria are not independent as the complexes, ES and EI, equilibrate with the same free enzyme pool, E. Increasing EI concentration by increasing the inhibitor concentration can be achieved only through a decrease in ES concentration, and vice versa: an elevated substrate concentration can increase the concentration of the ES complex only at the expense of the EI complex.
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