Enzyme Inhibition

The inhibition of the metabolism of one drug by another drug taken concurrently by the patient has now been shown to be a very important cause of adverse drug reactions (ADRs). In addition to the potential for drug–drug interactions leading to ADRs, the pharmaceutical industry is also very interested in enzyme inhibition as a basis for developing drugs that target specific enzymes of interest. This chapter focuses on approaches used to investigate the inhibition of the drug-metabolizing enzymes. Competitive inhibition occurs when the inhibitor binds reversibly to the enzyme and prevents the binding of the substrate to the catalytically active site of the enzyme. Transition-state analogs resemble the transition-state for the enzymatic reaction catalyzed by the enzyme. That is to say, they resemble the transient complex formed within the catalytic cycle that has the maximum free energy.