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)
Four cyclohexene analogues of gamma-aminobutyric acid (GABA) and beta-alanine were designed as conformationally rigid analogues of the epilepsy and
drug addiction
drug vigabatrin and as potential mechanism-based inactivators of
gamma-aminobutyric acid aminotransferase
(
GABA-AT
). The corresponding cyclopentene analogues were previously reported to be inhibitors, but not inactivators, of
GABA-AT
(Qiu, J.; Pingsterhaus, J.; Silverman, R. B. J. Med. Chem. 1999, 42, 4725-4728). cis-3-Aminocyclohex-4-ene-1-carboxylic acid (3) and cis-2-aminocyclohex-3-ene-1-carboxylic acid (5) showed time- and concentration-dependent, irreversible inactivation of
GABA-AT
. In both cases, the inactivations are protected by substrate, indicating that they are active site-directed. trans-3-Aminocyclohex-4-ene-1-carboxylic acid (4) and trans-2-aminocyclohex-3-ene-1-carboxylic acid (6) are not inactivators but are competitive reversible inhibitors of
GABA-AT
. Unlike the cyclopentene analogues, there appears to be sufficient ring flexibility to allow inactivation to occur. The orientation of the carboxylic and amino groups of these analogues is important for their binding to
GABA-AT
. Molecular modeling of
GABA-AT
with 3-6 and molecular dynamics simulations with vigabatrin bound provide rationalizations for the inhibitory properties of these compounds.
...
PMID:Inactivation and inhibition of gamma-aminobutyric acid aminotransferase by conformationally restricted vigabatrin analogues. 1223 32
In the mammalian central nervous system (CNS), the inhibitory GABAergic system is composed of different signaling molecules such as glutamate decaroxylase, vesicular GABA transporters, GABA receptors, GABA transporters and
GABA transaminase
. A prevailing view is that the balance between excitatory signaling mediated by glutamate and inhibitory signaling mediated by GABA plays a pivotal role in mechanisms underlying the modulation and maintenance of a variety of neural functions. Therefore, abnormalities in a GABAergic signaling molecule would lead to a crisis of severe symptoms relevant to a number of neuropsychiatric disorders. These include epilepsy, depression, schizophrenia, stiff-person syndrome,
drug addiction
and so on. In this review article, we will summarize recent studies on the relationship between the malfunction of GABAergic signaling molecules and the etiology of these neuropsychiatric disorders. We will also refer to novel strategies on GABAergic signaling molecules other than GABA receptors for therapeutic usefulness in the future.
...
PMID:[Neuropsychiatric disorders and GABA]. 1565 2
