XVlll 



CONTENTS 



CHAPTER S 



Determination 

 hibition 



of the Mechanisms and Constants of In- 



The Methods of Graphical Analysis .... 

 Generalized Equations for Determination of Constants 



Specific Types of Inhibition 



Determination of Constants Other than X, 



Isobolograms 



Mutual Depletion Systems ... . . 



Suggestions for Plotting and Determination of Constants 



149 



150 

 154 

 157 

 181 

 183 

 184 

 188 



CHAPTER 6 



Interactions of Inhibitors with Enzymes 193 



The Nature of Enzyme Active Centers 194 



Intermolecular Forces and Interaction Energy 204 



Relative Contributions of Different Interaction Forces 242 



Dielectric Constant 245 



Hydration of Ions 250 



Ionic Atmosphere . . 260 



Distortion Energy 262 



Inhibition Constants and Interaction Energy 264 



Determination of the Equilibrium Distance d^ from A',- 270 



Interactions of Haptens with Antibodies 274 



Interactions of Substrates and Inhibitors with Cholinesterase . . . 284 



Interaction Forces in Various Enzyme Systems 292 



Interactions of Aromatic Compounds 297 



Interactions of Hydrocarbon Chains 300 



Dependence of Interaction Energy upon Fit 301 



Effectsof Alteration of Structure on Molecular Properties 304 



Interactions of Small Molecules with Proteins 312 



Future Problems in Molecular Interactions 317 



CHAPTER 7 



Inhibition in Multienzyme Systems 319 



Concepts and Terminology 320 



Irreversible Monolinear Chains 322 



Partially and Completely Reversible Monolinear Chains 338 



Branched Linear Chains 340 



Polylinear Chains (Shunt System) . . . 345 



Distributive Systems 346 



Cyclic Systems 348 



Regenerative Systems 354 



Self-Regulatory or Feedback Systems 368 



Network Systems 372 



General Considerations of Multienzyme Systems 372 



