Disease relevance of ABAT

• cDNA encoding human 4-aminobutyrate aminotransferase (aminobutyrate:2-oxoglutarate aminotransferase) was prepared by polymerase chain reaction using mRNA from human neuroblastoma cells as the template and oligonucleotides synthesized on the basis of the information obtained from direct protein sequencing [1].
• The effects of increasing brain GABA with gamma-acetylenic GABA (GAG), a drug that inhibits GABA transaminase, were evaluated in ten patients with stable tardive dyskinesia during a blind placebo-controlled trial [2].
• Regional distribution of endogenous gamma-aminobutyric acid (GABA), its synthesizing enzyme, glutamic acid decarboxylase (GAD), and metabolic enzyme, GABA transaminase (GABA-T), were determined in the intestinal tract of guinea pigs and cats and the findings compared with the number of ganglion cells in Auerbach's plexus [3].
• The intensity of the GABA-T immunoreactivity had nearly disappeared in the interneurons at 12 h after ischemia [4].
• In untreated children, the seven with absences and the nine with simple partial seizures had a GABA-T activity of 6.9 +/- 3.3 and 7.8 +/- 3.2 pmol/min/mg, respectively, lower than the control group (P < 0.05) [5].

Psychiatry related information on ABAT

• Brain samples from patients with Huntington's chorea show no abnormal GABAT activity or unusual phenotypes [6].
• 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) [7].
• The activities of gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) were estimated in blood platelets from 25 male chronic alcoholics and from 27 healthy male volunteers without histories of alcohol abuse [8].
• It seems that the activity of GABA-T in the brain and/or in the blood platelets is correlated to certain neuropsychiatric disorders such as alcoholism, epilepsy, and Alzheimer's disease [9].
• Psychophysiological and psychometric studies after manipulating the GABA system by vigabatrin, a GABA-transaminase inhibitor [10].

High impact information on ABAT

• Twenty-four patients with frequent drug-resistant seizures took part in a randomised double-blind placebo-controlled crossover trial of the GABA-transaminase inhibitor, gamma-vinyl GABA [11].
• Evidence of single-marker association was found for variants in ABAT, CREBBP, and GRIN2A [12].
• The distribution of GABAT phenotypes was at Hardy-Weinberg equilibrium in all the ethnic groups studied [13].
• Pharmacological therapy in patients with this disorder has been limited to vigabatrin, an anticonvulsant that blocks GABA transaminase [14].
• GABA then is broken down, both within the cell and in the synaptic cleft by GABA transaminase to form succinic semialdehyde [15].

Chemical compound and disease context of ABAT

• 5. Experimental data suggest that the best prospect for potent anticonvulsant action with fewest side effects (myoclonus, sedation, ataxia) is at present offered by GABA-transaminase inhibitors or novel agents acting on the benzodiazepine receptor site [16].
• Vigabatrin, a GABA Transaminase Inhibitor, Reversibly Eliminates Tinnitus in an Animal Model [17].

Biological context of ABAT

• A human brain cDNA library constructed in the lambda ZAP II vector was screened using a fragment of pig brain cDNA encoding 4-aminobutyrate aminotransferase (pGaba-t) [18].
• Primary structure and tissue distribution of human 4-aminobutyrate aminotransferase [1].
• 5. The three banded patterns seen in heterozygotes suggest that GABAT is a dimeric enzyme [6].
• Site-directed mutagenesis of human brain GABA transaminase: lysine-357 is involved in cofactor binding at the active site [19].
• A survey compared syrup of ipecac use by CSPI, ABAT, and ABMT/ACMT members as the first response decontamination [20].

Anatomical context of ABAT

• 7. GABAT activity can be demonstrated in all areas of human brain with the exception of the corpus callosum [6].
• 2. GABAT isozymes can be detected in liver, brain, kidney, pancreas, heart, testis. spinal cord and upper jejunum [6].
• Interestingly, in the gastrodin-treated group, GABA transaminase (GABA-T) immunoreactivity in the hippocampus, particularly in neurons, was significantly decreased [21].
• GABA-T is present in a variety of circulating cells, including platelets and lymphocytes [22].
• SSADH, the final enzyme GABA catabolism, has been detected in some of the tissues in which GAD and GABA-T have been identified, although the presence of this enzyme has not been in mammalian pancreas, ova, oviduct, testis or sympathetic ganglia [23].

Associations of ABAT with chemical compounds

• 4-Aminobutyrate aminotransferase (GABA-transaminase, GABA-T, EC 2.6.1.19) deficiency (McKusick 137150), an inborn error of GABA degradation, has until now been documented in only a single Flemish child [24].
• Compared to the other defects of GABA degradation, succinic semialdehyde dehydrogenase (SSADH, EC 1.2.1.24) deficiency with > 150 patients (McKusick 271980) and pyridoxine-dependent seizures with > 100 patients ('putative' glutamic acid decarboxylase (GAD, EC 4.1.1.15) deficiency; McKusick 266100), GABA-T deficiency is very rare [24].
• Acute effects of valproate (VPA) and lamotrigine (LTG) on the uptake of GABA and the activity of GABA-T in platelets in vitro were also analyzed [25].
• 6. GABA, beta-alanine and 5-aminovaleric acid can act as substrates for GABAT [6].
• gamma-Aminobutyrate transaminase (GABA-T), a key enzyme of the GABA shunt, converts the major inhibitory neurotransmitter, GABA, to succinic semialdehyde [19].

Other interactions of ABAT

• Logistic regression analysis of SNP data across GRIN2A and ABAT showed a trend toward haplotypic differences between cases and controls [12].
• RECENT FINDINGS: The known clinical disorders of GABA metabolism are pyridoxine dependent epilepsy, GABA-transaminase deficiency, SSADH deficiency, and homocarnosinosis [26].
• CONCLUSION: In the hippocampi from patients with complex partial seizures the activities of the mitochondrial enzymes GABA-T and MAO-A were similar to those found in control subjects [27].
• In contrast, 24 h post-ischemia the dramatic augmentation of GABA-T immunoreactivity in the pyramidal cells was observed in the CA1 area but not in the CA2 or CA3 areas [4].
• An enhanced serum prolactin response to TRH in the presence of GABA transaminase inhibition [28].

Analytical, diagnostic and therapeutic context of ABAT

• Screening and sequence determination of a cDNA encoding the human brain 4-aminobutyrate aminotransferase [18].
• To identify the structural and functional roles of the cysteinyl residue at position 321, we constructed various GABA-T mutants by site-directed mutagenesis [29].
• The reactivity of GABA-AT crystals with the two GABA analogues was also investigated by polarized absorption microspectrophotometry [30].
• Six patients with different forms of dystonia were treated with gamma-vinyl GABA, a specific enzyme-activated inhibitor of GABA-transaminase, in a double-blind, placebo-controlled crossover study. gamma-Vinyl GABA therapy, 2 g daily for 2 weeks, was compared with placebo by weekly assessments [31].
• In a pilot single-blind study, gamma-vinyl GABA, an enzyme-activated irreversible inhibitor of GABA-transaminase (GABA-T), was administered orally to 10 epileptic patients who were refractory to conventional anticonvulsant therapy [32].

References