4 - Inhibitors and Activators

Abstract

This chapter discusses the mechanisms of inhibitors in enzyme-catalyzed reactions. Compounds that reduce the rate of an enzyme-catalyzed reaction when they are added to the reaction mixture are called inhibitors. Inhibition can arise in a wide variety of ways, however, and there are many different types of inhibitor. A class that is of little importance in enzyme kinetics (except as a nuisance) is that of irreversible inhibitors or catalytic poisons. A much more important class of inhibitors is that of reversible inhibitors. These inhibitors form dynamic complexes with the enzyme that have different catalytic properties from those of the free enzyme. For any mechanism, the most reliable method of determining which of the kinetic parameters is likely to be affected by an inhibitor is to derive the appropriate rate equation and examine it critically. Nonetheless, a more intuitive approach may also be helpful as a mnemonic. Most of the enzyme inhibitors that have been studied have been interpreted as linear inhibitors. Nonetheless, it is likely that there are many more exceptions than have been recognized, because the Botts–Morales scheme is very plausible, and it does not, in general, predict linear inhibition except under rather restrictive conditions. When considering the complete Botts–Morales scheme, it is convenient to treat inhibition and activation together, because the difference between them is quantitative rather than qualitative and the same algebra applies to both.