4 aminobutyrate transaminase

Summary

Summary: An enzyme that converts brain gamma-aminobutyric acid (GAMMA-AMINOBUTYRIC ACID) into succinate semialdehyde, which can be converted to succinic acid and enter the citric acid cycle. It also acts on beta-alanine. EC 2.6.1.19.

Top Publications

  1. Akihiro T, Koike S, Tani R, Tominaga T, Watanabe S, Iijima Y, et al. Biochemical mechanism on GABA accumulation during fruit development in tomato. Plant Cell Physiol. 2008;49:1378-89 pubmed publisher
    ..Taken together, our results suggest that GAD and GABA-TK play crucial roles in GABA accumulation and catabolism, respectively, in tomato fruits. ..
  2. Schor D, Struys E, Hogema B, Gibson K, Jakobs C. Development of a stable-isotope dilution assay for gamma-aminobutyric acid (GABA) transaminase in isolated leukocytes and evidence that GABA and beta-alanine transaminases are identical. Clin Chem. 2001;47:525-31 pubmed
    ..Our results with [15N]beta-alanine indicate that GABA and beta-alanine transaminases are identical. ..
  3. Jaeken J, Casaer P, De Cock P, Corbeel L, Eeckels R, Eggermont E, et al. Gamma-aminobutyric acid-transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. Neuropediatrics. 1984;15:165-9 pubmed
    ..Postmortem examination of his brain showed leukodystrophy of the type seen in amino acidopathies such as phenylketonuria. This appears to be the first report of gamma-aminobutyric acid-transaminase deficiency. ..
  4. Fait A, Yellin A, Fromm H. GABA shunt deficiencies and accumulation of reactive oxygen intermediates: insight from Arabidopsis mutants. FEBS Lett. 2005;579:415-20 pubmed
    ..These results provide novel evidence for the relationship between the GABA shunt and ROI, which may, in part, explain the phenotype of SSADH-deficient plants and animals...
  5. Jakobs C, Jaeken J, Gibson K. Inherited disorders of GABA metabolism. J Inherit Metab Dis. 1993;16:704-15 pubmed
  6. Bouche N, Fromm H. GABA in plants: just a metabolite?. Trends Plant Sci. 2004;9:110-5 pubmed
  7. Wu C, Zhou S, Zhang Q, Zhao W, Peng Y. Molecular cloning and differential expression of an gamma-aminobutyrate transaminase gene, OsGABA-T, in rice (Oryza sativa) leaves infected with blast fungus. J Plant Res. 2006;119:663-9 pubmed
    ..Our data suggest that OsGABA-T (GABA shunt) may play a role in restricting the levels of cell death during the host-pathogen interaction. ..
  8. De Biase D, Barra D, Simmaco M, John R, Bossa F. Primary structure and tissue distribution of human 4-aminobutyrate aminotransferase. Eur J Biochem. 1995;227:476-80 pubmed
    ..The human cDNA was used to probe for the presence of 4-aminobutyrate aminotransferase mRNA in human tissues and a significant transcript was found in heart, placenta and in tissues usually associated with the expression of this enzyme. ..
  9. Trudeau V, Kah O, Chang J, Sloley B, Dubourg P, Fraser E, et al. The inhibitory effects of (gamma)-aminobutyric acid (GABA) on growth hormone secretion in the goldfish are modulated by sex steroids. J Exp Biol. 2000;203:1477-85 pubmed
    ..Taken together, these results demonstrate that GABA has an inhibitory effect on growth hormone release in goldfish. ..

More Information

Publications62

  1. Abdulrazzaq Y, Padmanabhan R, Bastaki S, Ibrahim A, Bener A. Placental transfer of vigabatrin (gamma-vinyl GABA) and its effect on concentration of amino acids in the embryo of TO mice. Teratology. 2001;63:127-33 pubmed
    ..Methionine concentration is most severely affected in VGB-treated mothers, placentas, and fetuses. We speculate that this deficiency could be a possible mechanism for the teratogenic effects of vigabatrin. ..
  2. Krakow K, Polizzi G, Riordan Eva P, Holder G, Macleod W, Fish D. Recovery of visual field constriction following discontinuation of vigabatrin. Seizure. 2000;9:287-90 pubmed
    ..Larger scale clinical studies are needed to identify predictive factors both for the occurrence and reversibility of vigabatrin-associated visual field defects. ..
  3. Frosini M, Sesti C, Dragoni S, Valoti M, Palmi M, Dixon H, et al. Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain. Br J Pharmacol. 2003;138:1163-71 pubmed
    ..8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC(50)=3.72 micro M) and PSA GABA transaminase activity (IC(50)=103.0 micro M). 5. In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents. ..
  4. Sills G, Butler E, Forrest G, Ratnaraj N, Patsalos P, Brodie M. Vigabatrin, but not gabapentin or topiramate, produces concentration-related effects on enzymes and intermediates of the GABA shunt in rat brain and retina. Epilepsia. 2003;44:886-92 pubmed
    ..This phenomenon does not appear to extend to other GABAergic drugs, suggesting that these agents might not cause visual field defects. ..
  5. Yuan H, Silverman R. New substrates and inhibitors of gamma-aminobutyric acid aminotransferase containing bioisosteres of the carboxylic acid group: design, synthesis, and biological activity. Bioorg Med Chem. 2006;14:1331-8 pubmed
    ..Methylation of the tetrazole group in 8 resulted in loss of time-dependent activity, suggesting that the tetrazole ring, the carboxylate bioisostere, exists in its deprotonated form in the enzyme active site. ..
  6. Gibson J, Yarrington J, Loudy D, Gerbig C, Hurst G, Newberne J. Chronic toxicity studies with vigabatrin, a GABA-transaminase inhibitor. Toxicol Pathol. 1990;18:225-38 pubmed
    ..For this reason cerebrospinal fluid levels of GABA and vigabatrin were evaluated, with considerable species differences being noted. The significance of these differences in relation to the differences in toxic response is discussed. ..
  7. Pan Y, Calvert K, Silverman R. Conformationally-restricted vigabatrin analogs as irreversible and reversible inhibitors of gamma-aminobutyric acid aminotransferase. Bioorg Med Chem. 2004;12:5719-25 pubmed
    ..Two monofluorinated compounds, 4 and 5, are time-dependent inhibitors of the enzyme, and their potencies are comparable to that of vigabatrin. Compounds 6 and 7 are weak reversible inhibitors. ..
  8. Runquist M, Alonso G. Gabaergic signaling mediates the morphological organization of astrocytes in the adult rat forebrain. Glia. 2003;41:137-51 pubmed
    ..Taken together, these data strongly suggest that GABAergic signaling mediates the morphological organization of astrocytes and their expression of GFAP in the adult brain. ..
  9. Choi J, Lee D. A new citryl glycoside from Gastrodia elata and its inhibitory activity on GABA transaminase. Chem Pharm Bull (Tokyo). 2006;54:1720-1 pubmed
    ..Their structures were elucidated on the basis of spectroscopic data and chemical reaction. 1 inhibited GABA transaminase activity by 56.8% at the final concentration of 10 microg/ml. ..
  10. Weber J, Bolin R, Hixon M, Sherald A. Beta-alanine transaminase activity in black and suppressor of black mutations of Drosophila melanogaster. Biochim Biophys Acta. 1992;1115:181-6 pubmed
    ..The black mutation shows elevated levels of activity compared to wild type, while suppressor of black strains show decreased levels compared to wild type. ..
  11. De Biase D, Maras B, Bossa F, Barra D, John R. Protein structure of pig liver 4-aminobutyrate aminotransferase and comparison with a cDNA-deduced sequence. Eur J Biochem. 1992;208:351-7 pubmed
    ..The mammalian enzyme has approximately 44% sequence identity with the same enzyme from two unicellular eukaryotes (Saccharomyces cerevisiae, Aspergillus nidulans) and 22% identity with that from Escherichia coli. ..
  12. Storici P, Capitani G, De Biase D, Moser M, John R, Jansonius J, et al. Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy. Biochemistry. 1999;38:8628-34 pubmed
    ..The aldimines of GABA and the antiepileptic drug vinyl-GABA have been modeled into the active site. ..
  13. Liu W, Peterson P, Langston J, Jin X, Zhou X, Fisher A, et al. Kinetic and crystallographic analysis of active site mutants of Escherichia coli gamma-aminobutyrate aminotransferase. Biochemistry. 2005;44:2982-92 pubmed
  14. Hearl W, Churchich J. Interactions between 4-aminobutyrate aminotransferase and succinic semialdehyde dehydrogenase, two mitochondrial enzymes. J Biol Chem. 1984;259:11459-63 pubmed
  15. Zanjani H, Lemaigre Dubreuil Y, Tillakaratne N, Blokhin A, McMahon R, Tobin A, et al. Cerebellar Purkinje cell loss in aging Hu-Bcl-2 transgenic mice. J Comp Neurol. 2004;475:481-92 pubmed
  16. Toney M, Pascarella S, De Biase D. Active site model for gamma-aminobutyrate aminotransferase explains substrate specificity and inhibitor reactivities. Protein Sci. 1995;4:2366-74 pubmed
    ..The R isomer would direct the vinyl group toward Lys 329 and the C4-H bond toward Arg 445. The active site model presented provides a basis for site-directed mutagenesis and drug design experiments. ..
  17. Hardus P, Engelsman M, van Veelen C, Stilma J. [Vigabatrin: balancing effectiveness vs. (irreversible) visual field loss as a side effect]. Ned Tijdschr Geneeskd. 2000;144:2066-9 pubmed
    ..A careful judgement has to be made in individual patients before starting or continuing vigabatrin medication. ..
  18. Ha J, Lee D, Lee J, Kim J, Yong C, Kim J, et al. 4-Hydroxybenzaldehyde from Gastrodia elata B1. is active in the antioxidation and GABAergic neuromodulation of the rat brain. J Ethnopharmacol. 2000;73:329-33 pubmed
    ..It may be concluded that antioxidation and positive modulation of GABAergic neuromodulation of 4-hydroxybenzaldehyde partially contribute to an antiepileptic and anticonvulsive activity of G. elata B1. ..
  19. Kombian S, Edafiogho I, Ananthalakshmi K. Anticonvulsant enaminones depress excitatory synaptic transmission in the rat brain by enhancing extracellular GABA levels. Br J Pharmacol. 2005;145:945-53 pubmed
    ..Our data suggest that anticonvulsant enaminones cause EPSC depression by enhancing extracellular GABA levels possibly through the inhibition of either GABA reuptake or GABA-T enzyme, or both. ..
  20. Honda M, Inoue M, Okada Y, Yamamoto M. Alteration of the GABAergic neuronal system of the retina and superior colliculus in streptozotocin-induced diabetic rat. Kobe J Med Sci. 1998;44:1-8 pubmed
    ..The GABA content and GAD activity were reduced in the SC of STZ-treated rats, whereas GABA-T activity showed no marked change. This GABA reduction in the diabetes may be correlated with visual dysfunctions. ..
  21. Li D. Effects of iron deficiency on iron distribution and gamma-aminobutyric acid (GABA) metabolism in young rat brain tissues. Hokkaido Igaku Zasshi. 1998;73:215-25 pubmed
    ..This study provides evidence that iron deficiency in the brain could change the utilization and metabolism of GABA. ..
  22. Pearl P, Gibson K. Clinical aspects of the disorders of GABA metabolism in children. Curr Opin Neurol. 2004;17:107-13 pubmed
    ..SSADH deficiency has a heterogeneous spectrum and requires careful urine organic acid testing for screening, followed by enzymatic confirmation allowing appropriate prognostic and genetic counseling. ..
  23. Sergott R. Recommendations for visual evaluations of patients treated with vigabatrin. Curr Opin Ophthalmol. 2010;21:442-6 pubmed publisher
  24. De La Garza R, Zorick T, Heinzerling K, Nusinowitz S, London E, Shoptaw S, et al. The cardiovascular and subjective effects of methamphetamine combined with gamma-vinyl-gamma-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers. Pharmacol Biochem Behav. 2009;94:186-93 pubmed publisher
    ..Taken together, the data indicate that GVG treatment is generally well tolerated but not efficacious in attenuating the positive subjective effects of methamphetamine in the laboratory. ..
  25. Sherif F, Marcusson J, Oreland L. Brain gamma-aminobutyrate transaminase and monoamine oxidase activities in suicide victims. Eur Arch Psychiatry Clin Neurosci. 1991;241:139-44 pubmed
    ..01; P less than 0.05) was found in the hypothalamic region of the suicide victims. The difference seemed to be confined to the subgroup of suicides with a record of depressive disorder. ..
  26. Sherif F, Oreland L. Effects of chronic treatment with the GABA-transaminase inhibitor vigabatrin on exploratory behaviour in rats. Behav Brain Res. 1994;63:11-5 pubmed
    ..p.), 24 h after the last injection. However, in the plus-maze and open field tests, the effects of vigabatrin and diazepam on the general locomotor activity were not found to be decreased. ..
  27. Mauri Llerda J, Iniguez C, Tejero Juste C, Santos Lasaosa S, Escalza Cortina I, Ascaso Puyuelo J, et al. [Visual field changes secondary to vigabatrin treatment]. Rev Neurol. 2000;31:1104-8 pubmed
    ..Pallor of the optic nerve was seen in a group of patients. It is very important that serial campimetric studies are done for early detection of such alterations. ..
  28. Kushner S, Dewey S, Kornetsky C. The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats. J Pharmacol Exp Ther. 1999;290:797-802 pubmed
  29. Tursky T. Pyritinol and the enzymes of gamma-aminobutyric acid (GABA) synthesis and degradation. Physiol Bohemoslov. 1988;37:135-43 pubmed
    ..Pyritinol did not influence GABA transaminase activity, but lessened the oxidation of GABA to carbon dioxide. It is assumed that succinic semialdehyde dehydrogenase activity was inhibited. ..
  30. Martyniuk C, Awad R, Hurley R, Finger T, Trudeau V. Glutamic acid decarboxylase 65, 67, and GABA-transaminase mRNA expression and total enzyme activity in the goldfish (Carassius auratus) brain. Brain Res. 2007;1147:154-66 pubmed
    ..Our results show that GAD65, GAD67, and GABA-T mRNAs are generally correlated with total GAD and GABA-T activity and all three transcripts have a largely overlapping mRNA distribution in the goldfish forebrain. ..
  31. Wang Z, Yuan H, Nikolic D, van Breemen R, Silverman R. (+/-)-(1S,2R,5S)-5-Amino-2-fluorocyclohex-3-enecarboxylic acid. A potent GABA aminotransferase inactivator that irreversibly inhibits via an elimination-aromatization pathway. Biochemistry. 2006;45:14513-22 pubmed
    ..An elimination-aromatization mechanism is proposed to account for these results. ..
  32. Duboc A, Hanoteau N, Simonutti M, Rudolf G, Nehlig A, Sahel J, et al. Vigabatrin, the GABA-transaminase inhibitor, damages cone photoreceptors in rats. Ann Neurol. 2004;55:695-705 pubmed
    ..This study suggests that the visual field loss in vigabatrin-treated epileptic patients may result from a sequence of events starting from cone cell injury to a more severe disorganization of the photoreceptor layer. ..
  33. Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, et al. Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin. J Biol Chem. 2004;279:363-73 pubmed
    ..The spectral data are discussed in relation to the proposed mechanism. Intriguingly, all three structures revealed a [2Fe-2S] cluster of yet unknown function at the center of the dimeric molecule in the vicinity of the PLP cofactors...
  34. Gao Y, Lei L, Wu S. [Changes in GAT-3 and GABA-T mRNA expression of C6 glioma cells in response to a 2-week treatment with sodium valproate and withdrawal]. Di Yi Jun Yi Da Xue Xue Bao. 2003;23:885-7 pubmed
    ..36% +/-7.68%. Chronic treatment with VPA can down-regulate GAT-3 mRNA expression and up-regulate GABA-T mRNA expression in C6 glioma cells, and this undulation may involve VPA withdrawal rebound. ..
  35. Jones S, Palmer M. Activation of the tonic GABAC receptor current in retinal bipolar cell terminals by nonvesicular GABA release. J Neurophysiol. 2009;102:691-9 pubmed publisher
    ..The tonic GABA(C)R current in BC terminals exhibits similar properties to tonic GABA(A)R and glutamate receptor currents in the brain. ..
  36. Dewey S, Morgan A, Ashby C, Horan B, Kushner S, Logan J, et al. A novel strategy for the treatment of cocaine addiction. Synapse. 1998;30:119-29 pubmed
    ..Human trials with GVG are currently being developed to directly examine the utility of this novel strategy for the treatment of cocaine addiction. ..
  37. Pierantozzi M, Marciani M, Palmieri M, Brusa L, Galati S, Caramia M, et al. Effect of Vigabatrin on motor responses to transcranial magnetic stimulation: an effective tool to investigate in vivo GABAergic cortical inhibition in humans. Brain Res. 2004;1028:1-8 pubmed
    ..These data suggest that the great availability of synaptic GABA differently acts on the inhibitory circuitries controlled by different GABA-receptor subtypes. ..
  38. Koo B, Lee S, Ha J, Lee D. Inhibitory effects of the essential oil from SuHeXiang Wan on the central nervous system after inhalation. Biol Pharm Bull. 2004;27:515-9 pubmed
  39. Duffy S, Nguyen P, Baker G. Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices. Neuroscience. 2004;126:423-32 pubmed
    ..Thus, the inhibitory effects of PEH are state-dependent: hyper-excitation during epileptiform bursting was reduced, whereas synaptic transmission and plasticity were unaffected. ..
  40. Basu N, Scheuhammer A, Rouvinen Watt K, Evans R, Trudeau V, Chan L. In vitro and whole animal evidence that methylmercury disrupts GABAergic systems in discrete brain regions in captive mink. Comp Biochem Physiol C Toxicol Pharmacol. 2010;151:379-85 pubmed publisher
    ..Given that GABA is the main inhibitory neurotransmitter in the mammalian nervous system, prolonged disruptions of its function may underlie the sub-clinical impacts of MeHg at relevant levels to animal health...
  41. Awad R, Muhammad A, Durst T, Trudeau V, Arnason J. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytother Res. 2009;23:1075-81 pubmed publisher
    ..5% of the dry mass of the leaves. Synergistic effects may also play a role...
  42. Schneider B, Ruback S, Kiupakis A, Kasbarian H, Pybus C, Reitzer L. The Escherichia coli gabDTPC operon: specific gamma-aminobutyrate catabolism and nonspecific induction. J Bacteriol. 2002;184:6976-86 pubmed
    ..We propose that the gab operon and the Ntr response itself contribute to putrescine and polyamine homeostasis. ..
  43. Ortiz J, Negron A, Garcia M, Rosado J, Maldonaldo C. The C57BL/10Bg sps/sps mouse: a mutant with absence-like seizures; neurochemical and behavioral correlates. Neurosci Lett. 1990;114:231-6 pubmed
    ..Open field behavior of C57BL/10Bg sps/sps mice is characterized by periods of marked inactivity which easily distinguish affected homozygotes, from their heterozygotes littermates. ..
  44. Vetulani J. Drug addiction. Part III. Pharmacotherapy of addiction. Pol J Pharmacol. 2001;53:415-34 pubmed
    ..g. difficulties in introduction of methadone). ..
  45. Patel A, de Graaf R, Martin D, Battaglioli G, Behar K. Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo. J Neurochem. 2006;97:385-96 pubmed
    ..3-fold increase in inorganic phosphate, known to be a potent activator of apoGAD(65)in vitro. Our results are consistent with a major role for GAD(65) in activity-dependent GABA synthesis. ..
  46. Tao Y, Jiang D, Xu H, Yang X. Inhibitory effect of Erigeron breviscapus extract and its flavonoid components on GABA shunt enzymes. Phytomedicine. 2008;15:92-7 pubmed
    ..20+/-0.9 microM. The present results may imply new pharmacological actions of E. breviscapus and contribute partially to the beneficial effect of the herb and flavonoids on the central nervous system. ..
  47. Gerasimov M, Schiffer W, Gardner E, Marsteller D, Lennon I, Taylor S, et al. GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine. Eur J Pharmacol. 2001;414:205-9 pubmed
    ..Combined with our earlier findings, these studies support the potential therapeutic benefit of this enzyme-based GABAergic strategy to modulate brain dopamine and the subsequent treatment of drug addiction. ..
  48. Sulaiman S, Suliman F, Barghouthi S. Kinetic studies on the inhibition of GABA-T by gamma-vinyl GABA and taurine. J Enzyme Inhib Med Chem. 2003;18:297-301 pubmed
    ..The Michaelis-Menten constant (Km) in the absence of inhibition, was found to be 0.79 +/- 0.11 mM, and 0.47 +/- 0.10 mM for GABA and alpha-ketoglutarate respectively. ..
  49. Mausset Bonnefont A, de Seze R, Privat A. Immunohistochemistry as a tool for topographical semi-quantification of neurotransmitters in the brain. Brain Res Brain Res Protoc. 2003;10:148-55 pubmed
    ..This technique could be suitable for monitoring NT variations following any treatment. ..
  50. Choi S, Ahn E, Song M, Kim D, Kang J, Kwon O, et al. In vitro GABA-transaminase inhibitory compounds from the root of Angelica dahurica. Phytother Res. 2005;19:839-45 pubmed
    ..5 +/- 0.1 mm(-1) min(-1), respectively. It is postulated that imperatorin and falcarindiol are able to elevate the neurotransmitter GABA levels in the central nervous system by an inhibitory action on the GABA degradative enzyme GABA-T. ..
  51. Blum B, Mann J. The GABAergic system in schizophrenia. Int J Neuropsychopharmacol. 2002;5:159-79 pubmed
    ..Substantial evidence argues for a defect in the GABAergic system of the frontal cortex in schizophrenia which is limited to the parvalbumin-class of GABAergic interneurons. ..
  52. Bach B, Meudec E, Lepoutre J, Rossignol T, Blondin B, Dequin S, et al. New insights into {gamma}-aminobutyric acid catabolism: Evidence for {gamma}-hydroxybutyric acid and polyhydroxybutyrate synthesis in Saccharomyces cerevisiae. Appl Environ Microbiol. 2009;75:4231-9 pubmed publisher
    ..This study provides the first demonstration of a native route for the formation of this polymer in yeast. Our findings shed new light on the GABA pathway and open up new opportunities for industrial applications. ..
  53. Delmonte Corrado M, Ognibene M, Trielli F, Politi H, Passalacqua M, Falugi C. Detection of molecules related to the GABAergic system in a single-cell eukaryote, Paramecium primaurelia. Neurosci Lett. 2002;329:65-8 pubmed
    ..In vivo experiments suggested the involvement of GABA-related molecules in cell-cell interaction. ..