Open Access4‐Amino‐hex‐5‐enoic Acid, a Selective Catalytic Inhibitor of 4‐Aminobutyric‐Acid Aminotransferase in Mammalian Brain
Author(s) -
LIPPERT Bruce,
METCALF Brian W.,
JUNG Michel J.,
CASARA Patrick
Publication year - 1977
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1977.tb11410.x
Subject(s) - transaminase , enzyme , aminobutyric acid , pyridoxal phosphate , biochemistry , glutamate decarboxylase , alanine , pyridoxal , amino acid , pseudomonas fluorescens , substrate (aquarium) , chemistry , incubation , transamination , stereochemistry , biology , cofactor , bacteria , ecology , receptor , genetics
Incubation of rat brain 4‐aminobutyrate aminotransferase with 4‐amino‐hex‐5‐enoic acid, a substrate analog of 4‐aminobutyric acid, results in a time‐dependent irreversible loss of enzymatic activity. In the presence of 0.1 mM inhibitor the half‐life of the inactivation process is approximately 6 min. Low concentrations of L‐glutamic acid or 4‐aminobutyric acid protect against this inactivation. while 2‐oxoglutarate prevents this protection, suggesting that only the pyridoxal form of the enzyme is susceptible to inhibition by 4‐amino‐hex‐5‐enoic acid. The irreversible inhibition of mammalian 4‐aminobutyrate aminotransferase by 4‐amino‐hex‐5‐enoic acid is selective. There is no inhibition of this enzyme from Pseudomonas fluorescens with the inhibitor at mM concentrations. Even at 10 mM there is no irreversible inhibition of mammalian glutamate decarboxylase or of aspartate aminotransferase, while alanine aminotransferase is inhibited over 500 times more slowly than rat brain 4‐aminobutyrate transaminase.