EFFECTS OF ALTERATION OF STRUCTURE 



311 



Table 6-29 

 Dissociation Constants of Substrates and Inhibitors of a-CHYMOTRYPSiN " 



" From Manning and Niemann (1958). 



be attributed solely to a change in the inhibition of the enzymes sensitive 

 to iodoacetate or bromoacetate, whereas it actually reflects a new type of 

 action on the tricarboxylic acid cycle. Another example would be in the 

 testing of group substitutions in phenols on the inhibition of some enzyme. 

 The addition of most groups onto the ring would merely reflect different 

 interactions with the enzyme although with the same inhibition mechanism 

 whereas the introduction of a ^j-hydroxyl group would perhaps allow 

 inhibition by a new mechanism, namely the reaction with enzyme sulf- 

 hydryl groups through the formation of a quinone. 



General Suggestions with Regard to Comparison of Members 

 of an Inhibitor Series 



Summarizing the principles of this section, it must be emphasized that 

 great care be exercised in the interpretation of results on inhibition pro- 

 duced by homologous series and chemically related substances. The fol- 

 lowing points are believed to be particularly important for consideration 

 in work of this type. 



(a) Comparison of inhibition potencies must be made on a molar basis 

 and not on a weight /volume or dilution basis since it is only on the molar 

 basis that true relative activities and binding energy differences may be 

 obtained. 



(6) In most systems it is advisable to determine the effects of the various 

 members on the measured rate in the absence of the substrate, in order 

 to eliminate the possibility that some of the inhibitors are contributing 

 to the measurements by being acted upon by the enzyme in question or 

 by another enzyme in the preparation. This also serves to establish con- 

 trol determinations of the effects on any endogenous activity. 



