MISCELLANEOUS ANALOG INHIBITIONS 607 



Kynurenine Transaminase 



The transamination between kynurenine and a-ketoglutarate catalyzed 

 by an enzyme from rat kidney is inhibited by a variety of mono- and di- 

 carboxylates (Mason, 1959). The inhibitions are competitive with respect 

 to kynurenine and are reversible. The results are interpreted in terms of 



NAOP 



Fig. 2-21. Topographical scheme of 

 the active site of dehydroshikimate 

 reductase. (From BaHnsky and Da- 

 vies, 1961 b.) 



two types of interaction: (1) electrostatic binding of carboxylate groups to 

 cationic groups on the enzyme, and (2) van der Waals' forces between the 

 hydrocarbon portions of the inhibitors and the enzyme surface. The varia- 

 tion of inhibition in the dicarboxylate series (Table 2-40) indicates that two 

 cationic groups interact maximally with adipate. The distance between 

 these groups was given by Mason as 11 A on the basis of an extended adipate 

 molecule; the intercarboxylate distance for adipate is given as 6.87 A in 

 Table 1-1. However, the cationic groups need not be the same distance 

 apart as the carboxylate groups, and not only is the distance important 

 but the allowed configuration of the methylene chain to interact maximally 

 with the enzyme. As Mason points out, the data from the phthalates do 

 not support this distance entirely, since terephthalate inhibits least of the 

 three isomers and its intercarboxylate distance is the closest to that of 

 adipate. The intercarboxylate distance in isophthalate is 5.84 A (Table 1-1) 

 and this might indicate that the cationic groups are closer than might be 

 expected from the data on the flexible dicarboxylates, but again there is 

 the problem of the orientation of the benzene ring. The importance of van 

 der Waals' interactions is shown by the increasing inhibition given by the 

 higher fatty acids, and the greater inhibition by the alkyl-substituted glu- 



