GLUT AM ATE METABOLISM 331 



relatively weak (fumarate is included for comparison with values in the 

 preceding table). L-Glutamate was 2 mM in each case. The following are 

 not inhibitory at 10 mJ-l: L-glutamine, L-diethylglutamate, /?-methylglu- 

 tarate, citrate, o- and p-hydroxybenzoate. 



In the various substituted benzenes the 7neta compounds are invariably 

 the most potent inhibitors, presumably because the intergroup distances 

 are close to the enzyme intercationic separation. The dipoles of the halogen 

 and nitro compounds may interact with the cationic group since they may 

 be represented as: 



However, there is no correlation of inhibitory activity with dipole moment. 

 One might think that the dipole-cation interaction would be weaker than 

 the carboxylate-cation interaction, but the hydration of the inhibitors must 

 also be considered. Less water needs to be displaced when the dipoles ap- 

 proach the enzyme cationic group. It was pointed out that all good in- 

 hibitors are reasonably planar and the presence of bulky groups protruding 

 lowers the affinity. The particularly good binding of the furoates may be 

 related to some interaction of the ring with the enzyme. The reverse 

 reaction from or-ketoglutarate to glutamate is inhibited less than the for- 

 ward reaction by glutarate, isophthalate, and 5-bromofuroate, and the 

 inhibitions are noncompetitive. 



The L-glutamate dehydrogenase from cockroach muscle mitochondria 



