NATURE OF THE INTERMEDIATE COMPLEXES 



29 



restriction that is imposed on the movements of the molecule, as a whole 

 or intramolecularly, resulting in a decrease of entropy that may play an 

 important role in the energetics of activation. It would often be valuable 

 to know in what configuration the substrate is bound in the ES complex 

 when one is attempting to visualize the binding of inhibitors that interact 

 with the active center in a way comparable to the substrate. Is the substrate 



Fig. 2-5. Hypothetical energy contours 

 for various types of enzyme reactions. 

 The third situation might represent 

 transfer reactions, such as transphosphor- 

 ylation or transacetylation. The starred 

 complexes indicate activated states. 



bound in its normal most probable configuration or in a distorted configu- 

 ration conducive to reaction? In the binding of succinate, for example, are 

 the cationic groups on the dehydrogenase the same distance apart as the 

 normal distance between the carboxylate groups on the succinate, or is 

 the succinate bent or stretched into a form different from the one it would 

 statistically assume in solution? The interaction of competitively inhibiting 

 dicarboxylic acids, such as malonate, could be interpreted more quantita- 

 tively if this question could be answered definitely. 



