title: Inhibition of crayfish glutamic acid decarboxylase by structural analogs of the substrate and product.
abstract: Crayfish glutamic acid decarboxylase (GAD) is inhibited by some aliphatic carboxylic acid analogs of glutamate and gamma-amino-n-butyric acid (GABA). Variations in the length of the carbon skeleton, substitution of a keto for a methylene group, replacement of the carboxyl group or attachment of a bulky basic moiety to the amino terminus of GABA all lead to a drastic reduction in its inhibitory activity. Substitution of a methyl group for the amino group of GABA is a permissible alteration which does not reduce the inhibitory potency. Some structural analogs of glutamate are inhibitory also, particularly if they possess a comparable carbon skeleton and a keto group in the alpha position or a sulfhydryl group. Most of the sulfhydryl analogs are significantly more potent as inhibitors than the corresponding compounds in which the SH group is replaced by an H atom.
authors.forename: R M
authors.initials: RM
authors.lastname: Grossfeld
mesh_terms: D000818:Animals; D003400:Astacoidea; D002264:Carboxylic Acids / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D005971:Glutamates / Q000494:pharmacology; D007700:Kinetics; D009420:Nervous System / Q000201:enzymology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives
chemical_list: D002264:Carboxylic Acids; D005971:Glutamates; D013438:Sulfhydryl Compounds; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase