ABSTRACT
The topic of the inhibition of the enzymes of drug metabolism is of great interest to enzymologists, chemists, pharmacologists, and clinicians. The classic view of competitive inhibition is that the inhibitor shares structural similarity with the normal substrate. In classic non-competitive inhibition, the inhibitor binds to the enzyme at a site distinct from that of the substrate. Transition-state analogs are tight-binding, non-covalently bound inactivators that resemble the transition state for the enzymatic reaction; that is, the transient complex formed in a single step within the catalytic cycle with the maximum free energy. Many pharmaceutical companies routinely screen libraries of new chemical entities for inhibition early in the drug development process. Inhibition of the enzymes usually associated with drug metabolism is a subject of both basic and practical interest. Basic studies involve studies of mechanisms of catalysis and the utilization of selective inhibitors of individual forms of enzymes in multigene families.
