Enzyme Inhibitors

Enzymes catalyze the chemical reactions necessary for life. They typically increase chemical reaction rates by factors of 10¹⁰-10¹⁵. The first step to initiate catalysis is binding the reactant molecules into the catalytic sites to form the Michaelis complex. In most enzymes, a conformational change occurs to enclose the reactants tightly in the enzyme and to make contacts between reactants and the enzyme that will achieve the transition state and subsequently form products. The enzyme then relaxes to open the catalytic site and release products. Enzyme inhibitors prevent enzymes from their catalytic function by interfering with any step in the catalytic cycle. Four common types of enzyme inhibitors are given as follows: (1) catalytic site inhibitors that compete with the substrate for formation of the Michaelis complex, traditionally called competitive inhibitors; (2) inhibitors that alter formation of the Michaelis complex and full expression of catalytic potential are called noncompetitive inhibitors; (3) covalent inhibitors that form a Michaelis complex followed by a chemical reaction with the enzyme to form a stable and inactive complex, often called mechanism-based inhibitors or suicide inhibitors; and (4) transition-state analog inhibitors that resemble the unstable reactant complex at the transition state of the reaction.