Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.6.1.19 (
GABA transaminase
)
808
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The mechanism of inactivation of
gamma-aminobutyric acid aminotransferase
(
GABA-AT
) by L-3-chloroalanine hydroxamate (1) was investigated. Inactivation of [3H]PLP-reconstituted
GABA-AT
with 1 followed by denaturation gave no PMP or enamine adduct to the PLP; however, a new unknown metabolite was observed which was identical to the metabolite formed upon inactivation of
GABA-AT
by L-cycloserine. Time-dependent inactivation occurs, but the kinetics are second order; the rate of inactivation increases with time. After inactivation occurs the addition of fresh enzyme results in a faster rate of inactivation than prior to the initial inactivation. This indicates that the actual inactivator is generated from L-3-chloroalanine hydroxamate, and is not L-3-chloroalanine hydroxamate itself. Added gabaculine-inactivated enzyme to fresh enzyme does not increase the rate of inactivation, suggesting that the conversion of L-3-chloroalanine hydroxamate to the active form is not catalyzed by peripheral amino acid residues. L-
3-Chloroalanine
hydroxamate was shown to undergo buffer-catalyzed cyclization to L-cycloserine, which is the actual inactivator of
GABA-AT
.
...
PMID:Inactivation of gamma-aminobutyric acid aminotransferase by L-3-chloroalanine hydroxamate. 861 42
