Substrate analogues and divalent cations as inhibitors of glutamate decarboxylase from Escherichia coli.
To examine the idea that glutamate decarboxylase from E. coli can be a convenient source for the study of the effects of compounds on GABA synthesis in the nervous system, a series of substrate analogues and divalent cations were tested as potential inhibitors of the bacterial enzyme. Those analogues exhibiting inhibitor activity did so in a competitive manner. The most effective inhibitors were 3-mercaptopropionic acid, 4-bromoisophthalic acid and isophthalic acid which exhibited Ki values of 0.13 mM, 0.22 mM and 0.31 mM, respectively. Eight other analogues produced lesser degrees of inhibition. In addition, seven divalent metal cations were tested as inhibitors of the enzyme. However, only Hg2+, Cd2+, Cu2+ and Zn2+ were effective at a concentration of 0.1mM. When these results were compared to the patterns of inhibition of glutamate decarboxylase from mouse brain, certain differences in the manner in which the enzymes responded to the inhibitors, emerged. Consequently, the bacterial decarboxylase may not be a good model for the study of drug action on brain GABA synthesis.
Youngs
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Laboratory of Neurochemistry, Indiana University School of Medicine, Evansville 47712.
Tunnicliff
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D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology; D002413:Cations, Divalent / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D007124:Immunoenzyme Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D009474:Neurons; D010795:Phthalic Acids / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002413:Cations, Divalent; D010795:Phthalic Acids; C059768:isophthalate; C070348:4-bromoisophthalic acid; D015097:3-Mercaptopropionic Acid; D005968:Glutamate Decarboxylase