MISCELLANEOUS ANALOG INHIBITIONS 



609 



tarates compared to glutarate. One of the cationic groups on the enzyme 

 seems to have a pK,, around 6.7, since the mhibition by the dicarboxylates 

 decreases from pH 5.5 to 8.5 and approaches that of the monocarboxylates 

 (Fig. 2-22). The increase in inhibition of the dicarboxylates with longer 

 chain lengths than suberate is explained by the ability of the flexible hy- 

 drocarbon portions to orient for effective interaction with the enzyme sur- 

 face between or around the cationic groups. The contribution of a methyl- 

 ene group to the binding is around 0.2-0.4 kcal/mole. It is likely that a 



100 



VALERATE 



5.5 



6.0 



6.5 



7.0 



7.5 



8.0 



8.5 



pH 



Fig. 2-22. Effects of pH on the inhibitions of kynurenine transaminase by 

 various fatty acid anions at 6 mM. (From Mason, 1959.) 



hydrophobic region of the enzyme lies at some distance from the cationic 

 groups since the fatty acids do not begin to inhibit until the chain length 

 reaches 5 or 6 carbon atoms, and the marked differences between the bind- 

 ing energies of benzoate and y-phenylbutyrate, and cyclohexanecarboxylate 

 and y-cyclohexanebutyrate, indicate that the ring interaction is effective 

 when the ring is separated from the carboxylate group by several angstroms. 

 However, these differences may be due more to steric factors, a ring close 

 to the carboxylate group interfering with its electrostatic interaction. In- 

 deed, there seems to be a region for van der Waals' interactions between the 



