Kinetics of Enzyme Action Essential Principles for Drug Hunters [Hardcover]

Few scientists have the knowledge to perform the studies that are necessary to discover and characterize enzyme inhibitors, despite the vested interest the pharmaceutical industry has in this field. Beginning with the most basic principles pertaining to simple, one-substrate enzyme reactions and their inhibitors, and progressing to a thorough treatment of two-substrate enzymes, Kinetics of Enzyme Action: Essential Principles for Drug Hunters provides biochemists, medicinal chemists, and pharmaceutical scientists with numerous case study examples to outline the tools and techniques necessary to perform, understand, and interpret detailed kinetic studies for drug discovery.Preface xi

1 INTRODUCTION 1

1.1 A Brief History of Enzymology 2

1.2 Goal of Enzymology: The Elucidation of Mechanism 11

1.3 The Emergence of Mechanism from Data 13

2 KINETICS OF SINGLE-SUBSTRATE ENZYMATIC REACTIONS 19

2.1 The Dependence of Initial Velocity on Substrate Concentration and the Requirement for an E: S Complex 19

2.2 Derivation of the Rate Equation for a Single-Substrate Reaction with the Assumption of Rapid Equilibrium 21

2.3 Derivation of Rate Equations Using the Steady-State Assumption 24

2.4 Methods of Enzyme Assay 26

2.5 Enzyme Kinetics Practicum: Assay Development, Experimental Design, Data Collection, and Data Analysis 32

3 KINETICS OF SINGLE-SUBSTRATE ENZYMATIC REACTIONS: SPECIAL TOPICS 41

3.1 Transition State Theory and Free Energy Diagrams 41

3.2 Kinetic Consequences of an Enzyme: Substrate Complex 46

3.3 Reactions with More Than One Intermediary Complex 51

3.4 Deviations from Michaelis–Menten Kinetics 5l(