TAILIEUCHUNG - Enzyme Inhibitors

Compounds that influence the rates of enzyme-catalyzed reactions are called modulators, moderators, or modifiers. Usually, the effect is to reduce the rate, and this is called inhibition. Sometimes the enzyme reaction is increased, and this is called activation. Accordingly, the compounds are termed inhibitors or activators. When studying these phenomena, one has to understand the molecular events. | 4 Enzyme Inhibitors Jure Stojan CONTENTS Introduction Types of Inhibitors Reversible Inhibitors Transition-State Analogs Irreversible Inhibitors Kinetics of Inhibited Enzyme Reactions Classical Instantaneous Inhibition Mechanisms Types of Mechanisms Determination of Inhibition Constants Nonproductive Binding and Substrate Inhibition More General Reaction Mechanisms Slow Inhibition Slow Tight-Binding Inhibition Irreversible Inhibition Inhibited Two-Substrate Reactions References INTRODUCTION Compounds that influence the rates of enzyme-catalyzed reactions are called modulators moderators or modifiers. Usually the effect is to reduce the rate and this is called inhibition. Sometimes the enzyme reaction is increased and this is called activation. Accordingly the compounds are termed inhibitors or activators. When studying these phenomena one has to understand the molecular events leading to the experimentally observed effects. A number of techniques are available for reaching a basic explanation for the so-called mechanism or mode of action of a substance on the enzymic reaction under investigation. Although the methods for solving the 3-D structure of enzyme-inhibitor complexes result in clear steric presentations and quantum mechanical calculations provide data consistent with basic physicochemical laws the great practical value of classical kinetic information cannot and must not be neglected. Additionally it should be stressed that not only the mode of action of an inhibitor is important but its effects on the substrate turnover in many cases provide information that cannot be obtained from studies of pure enzymesubstrate systems. On the basis of such kinetic observations inhibitors are usually 2005 by CRC Press divided into two groups. The first consists of reversible inhibitors that form nonco-valent interactions with various parts of the enzyme surface which can be .

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