GLUTAMATE METABOLISM 



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GLUTAMATE METABOLISM 



Glutamate occupies a central position in many important metabolic 

 pathways and serves to link amino acid metabolism with the tricarboxylic 

 acid cycle. Its relationship to the biochemically active glutamine and the 

 physiologically active /-aminobutyrate (GABA) makes possible specific 

 inhibitions of glutamate reactions of great interest. The reactions catalyzed 

 by enzymes studied with respect to analog inhibition are shown in the 

 following scheme. 



glutamylhydroxamate 



D -glutamate 



(4) 

 o-ketoglutarate 



(7) 

 (3) (8) 



glutamine 



(6) 



(1,2) 



L-glutamate — 



(5) 



r 

 >' -aminobuty rate 



(10) 



proline 



A'-pyrroline-5-carboxylate 



a 



(10) 

 glutamic -7 -semialdehyde 



(1) L-glutamate dehydrogenase 



(2) glutamate transaminases 



(3) glutamate racemase 



(4) D-glutamate oxidase 



(5) glutamate decarboxylase 



(6) glutamine synthetase 



(7) glutaminase 



(8) formylglycinamidine phosphoriboside synthetase 



(9) 7 -glutamyl transferase 



(10) A'-pyrroline-5-carboxylate dehydrogenase 



Glutamate Decarboxylase 



Several analogs of glutamate inhibit its utilization by Lactobacillus ara- 

 binosus, and thus a study of decarboxylase from E. coli was undertaken 

 by Roberts (1953). The two most potent inhibitors are a-oximinoglutarate 

 and a-methylglutamate, but the former is probably active by virtue of 

 its hydrolysis to hydroxylamine which inactivates pyridoxal phosphate. 

 The latter analog inhibits competitively when added with the substrate, 

 but if it is preincubated with the enzyme the inhibition becomes progres- 

 sively more noncompetitive and difficulty reversible. The rates of combina- 

 tion with the enzyme and dissociation from the enzyme are very slow. 

 The methyl group interferes with the normal binding of the molecule so 

 that decarboxylation does not occur, but by some unknown mechanism 

 brings about a type of binding that is very strong, a behavior seen with 

 some other a-methylamino acids. The decarboxylation of glutamate in 

 rat brain homogenates is also inhibited competitively by aspartate {K„^ 



