GLUTAMATE METABOLISM 329 



inhibition by acetate is surprising; if the monocarboxylates interact with 

 the cationic groups, one might expect propionate or butyrate to be more 

 inhibitory. 



The problem of the abnormal brain development in phenylpyruvic oligo- 

 phrenia prompted an investigation of the effects of the phenyl acids on 

 brain glutamate decarboxylase by Hanson (1958); the results are presented 

 in the tabulation below in which they are compared with those of Tashian 



Inhibitor 



p-Hydroxyphenylacetate 



o-Hydroxyphenylacetate 



Phenylpyruvate 



Phenylacetate 



p-Hydroxyphenylpyruvate 



Phenylalanine 



Phenyllactate 



° Relative — AF's of binding adjusted so that value for phenylpyruvate is the same 

 in each series. 



(1961), who also used rat brain. There are some rather striking differences, 

 part of which may be due to the procedures used since these analogs, 

 although stated to be competitive, present deviations from classic kinetic 

 formulations (and for this reason the binding energies calculated from ap- 

 parent K/s are probably not very reliable). If these analogs, which are 

 present in high concentrations in the blood enter the brain readily, it is 

 possible that they depress the formation of y-aminobutyrate (GABA) 

 which may be essential for normal neurological development. In branched- 

 chain ketonuria (maple sugar urine disease) various keto and hydroxy 

 fatty acids accumulate in the body, which Tashian (1961) showed also 

 inhibit glutamate decarboxylase (relative — JF's of binding for a-hydroxy- 

 isovalerate, a-ketoisovalerate, and the corresponding isocaproates from 

 3.58 to 4.50 kcal/mole on the scale above). The enzyme from E. coli, on 

 the other hand, is relatively insensitive to any of these analogs. 



L-Glutamate Dehydrogenase 



The oxidative deamination of L-glutamate in beef liver homogenates is 

 catalyzed by a NAD-linked dehydrogenase, the inhibition of which at 

 pH 8.4 was thoroughly studied by Caughey et al. (1957). The accompanying 

 tabulation shows the K^ values for competitive analogs, from which the 



