PREFACE 



For those rare readers who may feel inclined to pursue their way through 

 Volumes II and III from beginning to end, I have tried to arrange the 

 chapters and sections in a logical and interdependent order. Malonate has 

 been approached first because its actions so well illustrate some of the 

 general principles covered in Volume I, and, indeed, malonate is discussed 

 in greater detail than any other inhibitor in order to suggest how one 

 would like to deal with all inhibitors if one had either the time or space. 

 Inasmuch as malonate is the classic substrate analog, the next chapter 

 takes up various types of analogs and here we are able to obtain some 

 rough idea of the energies involved in the interactions of inhibitors with 

 enzyme surfaces, as well as study some of the factors which determine 

 specificity. Some readers may feel that too much attention has been given 

 to these analogs, but I believe they represent a very important group of 

 inhibitors and illustrate many principles — competitive behavior, group 

 specific interactions, protection and reversal, and even mutual depletion 

 kinetics since some analogs are extremely potent inhibitors — and, in 

 addition, contribute to our understanding of feedback inhibition and me- 

 tabolic regulation. Most of the remainder of the volumes is devoted to sub- 

 stances considered to react with SH groups, certainly one of the most 

 commonly used and important classes of inhibitors, about which it is sur- 

 prisingly difficult to find adequate and comprehensive treatment. Certain 

 aspects of inhibition have been treated in detail, not necessarily because 

 of any intrinsic importance, but because of the information which is 

 provided to help us comprehend the general phenomena of inhibition. 

 There are many ways of writing about inhibitors, and I have tried to alter 

 the approach according to what I believe to be the most interesting aspects 

 of each inhibitor. These aspects may not happen to be those which would 

 have been chosen by the reader, but it is impossible to cover any inhibitor 

 completely and present it from all viewpoints. On the other hand, there 

 are certain sections which I have been unable to make very interesting, 

 to organize into a coherent picture, sometimes because the data are insuf- 

 ficient or too heterogeneous, but nevertheless some worthwhile material 



