CHAPTER 17 



SUGGESTIONS FOR PLANNING 

 AND REPORTING INHIBITION STUDIES 



The information that may be obtained from work with enzyme inhibitors 

 is greater in magnitude and reliability when the inhibitors are used correct- 

 ly. The investigation of metabolic inhibition, like any work with biologi- 

 cal systems, is inherently difficult, and anyone who is acquainted with this 

 field will know that in order to achieve significant results, especially in 

 living cells or tissues, much careful experimentation must be done and 

 thorough consideration must be given to the many factors that may com- 

 plicate the interpretations. Furthermore, a complete and intelligible report 

 of the work is necessary if the results are to be made useful to others. The 

 following practical suggestions may help those who have not worked ex- 

 tensively with inhibitors to obtain the maximal reliable information and 

 are based on personal experience and mistakes, as well as on the consider- 

 ation of several thousand reports in the literature. Such advice might be 

 taken as presumptuous but even a casual survey of the majority of inhibition 

 studies will demonstrate certain deficiencies and occasionally a rather 

 naive approach. Inhibitors are at present so widely used to characterize 

 enzymes, to plot metabolic sequences, and to correlate cellular functions 

 with the metabolism, that it is perhaps time to suggest that inhibitors 

 should either be used carefully and thoroughly, or not used at all, and that 

 interpretations of the data be made with a full realization of the com- 

 plexities of the systems studied. The following remarks are partly supple- 

 mentary to what has already been written in the iDrevious chapters and 

 must, of course, be taken in light of the purpose and nature of the investi- 

 gations to be undertaken. Specific failures to observe certain simple pre 

 cautions and various types of interiDretative errors will be illustrated in 

 the later volumes. 



SUGGESTIONS PARTICULARLY APPLICABLE 

 TO INHIBITIONS OF PURIFIED ENZYMES 



(1) Determine initial enzyme rates. It is very important to determine as 

 far as possible the effects of inhibitors on the initial rates following the 



879 



