Record Information |
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Version | 2.0 |
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Created at | 2005-11-16 15:48:42 UTC |
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Updated at | 2022-01-01 17:45:32 UTC |
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NP-MRD ID | NP0000970 |
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Secondary Accession Numbers | None |
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Natural Product Identification |
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Common Name | gamma-Aminobutyric acid |
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Description | Gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter found in the nervous systems of widely divergent species, including humans. It is the chief inhibitory neurotransmitter in the vertebrate central nervous system. In vertebrates, GABA acts at inhibitory synapses in the brain. It acts by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neurons. This binding causes the opening of ion channels to allow either the flow of negatively-charged chloride ions into the cell or positively-charged potassium ions out of the cell. This will typically result in a negative change in the transmembrane potential, usually causing hyperpolarization. Three general classes of GABA receptor are known (PMID: 10561820 ). These include GABA-A and GABA-C ionotropic receptors, which are ion channels themselves, and GABA-B metabotropic receptors, which are G protein-coupled receptors that open ion channels via intermediaries known as G proteins (PMID: 10561820 ). Activation of the GABA-B receptor by GABA causes neuronal membrane hyperpolarization and a resultant inhibition of neurotransmitter release. In addition to binding sites for GABA, the GABA-A receptor has binding sites for benzodiazepines, barbiturates, and neurosteroids. GABA-A receptors are coupled to chloride ion channels. Therefore, activation of the GABA-A receptor induces increased inward chloride ion flux, resulting in membrane hyperpolarization and neuronal inhibition (PMID: 10561820 ). After release into the synapse, free GABA that does not bind to either the GABA-A or GABA-B receptor complexes can be taken up by neurons and glial cells. Four different GABA membrane transporter proteins (GAT-1, GAT-2, GAT-3, and BGT-1), which differ in their distribution in the CNS, are believed to mediate the uptake of synaptic GABA into neurons and glial cells. The GABA-A receptor subtype regulates neuronal excitability and rapid changes in fear arousal, such as anxiety, panic, and the acute stress response (PMID: 10561820 ). Drugs that stimulate GABA-A receptors, such as the benzodiazepines and barbiturates, have anxiolytic and anti-seizure effects via GABA-A-mediated reduction of neuronal excitability, which effectively raises the seizure threshold. GABA-A antagonists produce convulsions in animals and there is decreased GABA-A receptor binding in a positron emission tomography (PET) study of patients with panic disorder. Neurons that produce GABA as their output are called GABAergic neurons and have chiefly inhibitory action at receptors in the vertebrate. Medium spiny neurons (MSNs) are a typical example of inhibitory CNS GABAergic cells. GABA has been shown to have excitatory roles in the vertebrate, most notably in the developing cortex. Organisms synthesize GABA from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate as a cofactor (PMID: 12467378 ). It is worth noting that this involves converting the principal excitatory neurotransmitter (glutamate) into the principal inhibitory one (GABA). Drugs that act as agonists of GABA receptors (known as GABA analogs or GABAergic drugs), or increase the available amount of GABA typically have relaxing, anti-anxiety, and anti-convulsive effects. GABA is found to be deficient in cerebrospinal fluid and the brain in many studies of experimental and human epilepsy. Benzodiazepines (such as Valium) are useful in status epilepticus because they act on GABA receptors. GABA increases in the brain after administration of many seizure medications. Hence, GABA is clearly an antiepileptic nutrient. Inhibitors of GAM metabolism can also produce convulsions. Spasticity and involuntary movement syndromes, such as Parkinson's, Friedreich's ataxia, tardive dyskinesia, and Huntington's chorea, are all marked by low GABA when amino acid levels are studied. Trials of 2 to 3 g of GABA given orally have been effective in various epilepsy and spasticity syndromes. Agents that elevate GABA are also useful in lowering hypertension. Three grams orally have been effective in controlling blood pressure. GABA is decreased in various encephalopathies. GABA can reduce appetite and is decreased in hypoglycemics. GABA reduces blood sugar in diabetics. Chronic brain syndromes can also be marked by deficiencies of GABA. Vitamin B6, manganese, taurine, and lysine can increase both GABA synthesis and effects, while aspartic acid and glutamic acid probably inhibit GABA effects. Low plasma GABA has been reported in some depressed patients and may be a useful trait marker for mood disorders. GABA has an important role in embryonic development, especially facial development, as substantiated by the association of a cleft palate in transgenic mice deficient in GAD67 (glutamate decarboxylase). A recent Japanese population study reported linkage in patients with a nonsyndromic cleft lip with or without a cleft palate and specific GAD67 haplotypes (PMID: 23842532 ). Unusually high levels of GABA (especially in the brain) can be toxic and GABA can function as both a neurotoxin and a metabotoxin. A neurotoxin is a compound that damages the brain and/or nerve tissue. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of GABA are associated with at least five inborn errors of metabolism, including D-2-hydroxyglutaric aciduria, 4-hydroxybutyric aciduria/succinic semialdehyde dehydrogenase deficiency, GABA-transaminase deficiency, homocarnosinosis, and hyper beta-alaninemia. Nearly all of these conditions are associated with seizures, hypotonia, intellectual deficits, macrocephaly, encephalopathy, and other serious neurological or neuromuscular problems. Increased levels of GABA seem to alter the function of the GABA-B receptor, which may play a role in the tonic-clonic seizures that are often seen in patients with the above disorders. |
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Structure | InChI=1S/C4H9NO2/c5-3-1-2-4(6)7/h1-3,5H2,(H,6,7) |
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Synonyms | Value | Source |
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4-Aminobutanoic acid | ChEBI | 4-Aminobutyric acid | ChEBI | 4Abu | ChEBI | GABA | ChEBI | GAMMA-AMINO-butanoIC ACID | ChEBI | gamma-Amino-N-butyric acid | ChEBI | gamma-Aminobutanoic acid | ChEBI | gamma-Aminobuttersaeure | ChEBI | Omega-aminobutyric acid | ChEBI | Piperidic acid | ChEBI | Piperidinic acid | ChEBI | 4-Aminobutyrate | Kegg | Gammalon | Kegg | 4-Aminobutanoate | Generator | g-AMINO-butanoate | Generator | g-AMINO-butanoic acid | Generator | gamma-AMINO-butanoate | Generator | Γ-amino-butanoate | Generator | Γ-amino-butanoic acid | Generator | g-Amino-N-butyrate | Generator | g-Amino-N-butyric acid | Generator | gamma-Amino-N-butyrate | Generator | Γ-amino-N-butyrate | Generator | Γ-amino-N-butyric acid | Generator | g-Aminobutanoate | Generator | g-Aminobutanoic acid | Generator | gamma-Aminobutanoate | Generator | Γ-aminobutanoate | Generator | Γ-aminobutanoic acid | Generator | g-Aminobuttersaeure | Generator | Γ-aminobuttersaeure | Generator | Omega-aminobutyrate | Generator | Piperidate | Generator | Piperidinate | Generator | g-Aminobutyrate | Generator | g-Aminobutyric acid | Generator | gamma-Aminobutyrate | Generator | Γ-aminobutyrate | Generator | Γ-aminobutyric acid | Generator | 3-Carboxypropylamine | HMDB | Aminalon | HMDB | Gaballon | HMDB | Gamarex | HMDB | gamma Aminobutyrate | HMDB | gamma Aminobutyric acid | HMDB | Gammalone | HMDB | Gammar | HMDB | Gammasol | HMDB | Mielogen | HMDB | Mielomade | HMDB | W-Aminobutyrate | HMDB | W-Aminobutyric acid | HMDB | gamma-Aminobutyric acid, calcium salt (2:1) | HMDB | gamma-Aminobutyric acid, hydrochloride | HMDB | gamma-Aminobutyric acid, zinc salt (2:1) | HMDB | 4 Aminobutanoic acid | HMDB | 4 Aminobutyric acid | HMDB | Lithium gaba | HMDB | gamma Aminobutyric acid, monolithium salt | HMDB | gamma Aminobutyric acid, monosodium salt | HMDB | gamma-Aminobutyric acid, monolithium salt | HMDB | gamma-Aminobutyric acid, monosodium salt | HMDB | Acid, hydrochloride gamma-aminobutyric | HMDB | Aminalone | HMDB | GABA, lithium | HMDB | Hydrochloride gamma-aminobutyric acid | HMDB | gamma Aminobutyric acid, hydrochloride | HMDB | 4-Amino-butanoate | HMDB | gamma-Aminobutyric acid | KEGG |
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Chemical Formula | C4H9NO2 |
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Average Mass | 103.1198 Da |
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Monoisotopic Mass | 103.06333 Da |
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IUPAC Name | 4-aminobutanoic acid |
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Traditional Name | gamma(amino)-butyric acid |
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CAS Registry Number | 56-12-2 |
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SMILES | NCCCC(O)=O |
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InChI Identifier | InChI=1S/C4H9NO2/c5-3-1-2-4(6)7/h1-3,5H2,(H,6,7) |
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InChI Key | BTCSSZJGUNDROE-UHFFFAOYSA-N |
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Experimental Spectra |
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| Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
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1D NMR | 1H NMR Spectrum (1D, 700 MHz, H2O, simulated) | Ahselim | | | 2022-01-01 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 600 MHz, H2O, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum | 2D NMR | [1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum |
| Predicted Spectra |
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| Not Available | Chemical Shift Submissions |
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| Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
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1D NMR | 13C NMR Spectrum (1D, 400 MHz, H2O, simulated) | varshavi.d26@gmail.com | Not Available | Not Available | 2021-08-07 | View Spectrum |
| Species |
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Species of Origin | |
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Species Where Detected | |
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Chemical Taxonomy |
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Description | Belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom. |
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Kingdom | Organic compounds |
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Super Class | Organic acids and derivatives |
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Class | Carboxylic acids and derivatives |
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Sub Class | Amino acids, peptides, and analogues |
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Direct Parent | Gamma amino acids and derivatives |
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Alternative Parents | |
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Substituents | - Gamma amino acid or derivatives
- Amino fatty acid
- Straight chain fatty acid
- Fatty acid
- Fatty acyl
- Amino acid
- Monocarboxylic acid or derivatives
- Carboxylic acid
- Organic oxide
- Organopnictogen compound
- Primary amine
- Organooxygen compound
- Organonitrogen compound
- Primary aliphatic amine
- Organic oxygen compound
- Carbonyl group
- Organic nitrogen compound
- Amine
- Hydrocarbon derivative
- Aliphatic acyclic compound
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Molecular Framework | Aliphatic acyclic compounds |
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External Descriptors | |
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Physical Properties |
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State | Solid |
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Experimental Properties | Property | Value | Reference |
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Melting Point | 203 °C | Not Available | Boiling Point | Not Available | Not Available | Water Solubility | 1300 mg/mL | Not Available | LogP | -3.17 | Hansch CH, Leo A and Hoekman DH. "Exploring QSAR: Hydrophobic, Electronic, and Steric Constraints. Volume 1" ACS Publications (1995). |
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Predicted Properties | |
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General References | - Zarnowska ED, Pearce RA, Saad AA, Perouansky M: The gamma-subunit governs the susceptibility of recombinant gamma-aminobutyric acid type A receptors to block by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N). Anesth Analg. 2005 Aug;101(2):401-6, table of contents. [PubMed:16037152 ]
- Levy LM, Levy-Reis I, Fujii M, Dalakas MC: Brain gamma-aminobutyric acid changes in stiff-person syndrome. Arch Neurol. 2005 Jun;62(6):970-4. [PubMed:15956168 ]
- Hasler G, Neumeister A, van der Veen JW, Tumonis T, Bain EE, Shen J, Drevets WC, Charney DS: Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy. Biol Psychiatry. 2005 Dec 15;58(12):969-73. Epub 2005 Jul 25. [PubMed:16043137 ]
- Denda M, Inoue K, Inomata S, Denda S: gamma-Aminobutyric acid (A) receptor agonists accelerate cutaneous barrier recovery and prevent epidermal hyperplasia induced by barrier disruption. J Invest Dermatol. 2002 Nov;119(5):1041-7. [PubMed:12445190 ]
- Wiens SC, Trudeau VL: Thyroid hormone and gamma-aminobutyric acid (GABA) interactions in neuroendocrine systems. Comp Biochem Physiol A Mol Integr Physiol. 2006 Jul;144(3):332-44. Epub 2006 Mar 9. [PubMed:16527506 ]
- Choi C, Coupland NJ, Hanstock CC, Ogilvie CJ, Higgins AC, Gheorghiu D, Allen PS: Brain gamma-aminobutyric acid measurement by proton double-quantum filtering with selective J rewinding. Magn Reson Med. 2005 Aug;54(2):272-9. [PubMed:16032672 ]
- Metzeler K, Agoston A, Gratzl M: An Intrinsic gamma-aminobutyric acid (GABA)ergic system in the adrenal cortex: findings from human and rat adrenal glands and the NCI-H295R cell line. Endocrinology. 2004 May;145(5):2402-11. Epub 2004 Jan 15. [PubMed:14726441 ]
- Naini AB, Vontzalidou E, Cote LJ: Isocratic HPLC assay with electrochemical detection of free gamma-aminobutyric acid in cerebrospinal fluid. Clin Chem. 1993 Feb;39(2):247-50. [PubMed:8432013 ]
- Levy LM, Henkin RI: Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy. J Comput Assist Tomogr. 2004 Nov-Dec;28(6):721-7. [PubMed:15538143 ]
- Rating D, Siemes H, Loscher W: Low CSF GABA concentration in children with febrile convulsions, untreated epilepsy, and meningitis. J Neurol. 1983;230(4):217-25. [PubMed:6198481 ]
- Spanaki MV, Siegel H, Kopylev L, Fazilat S, Dean A, Liow K, Ben-Menachem E, Gaillard WD, Theodore WH: The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism. Neurology. 1999 Oct 22;53(7):1518-22. [PubMed:10534261 ]
- Campollo O, MacGillivray BB, McIntyre N: [Association of plasma ammonia and GABA levels and the degree of hepatic encephalopathy]. Rev Invest Clin. 1992 Oct-Dec;44(4):483-90. [PubMed:1485027 ]
- Nicholson-Guthrie CS, Guthrie GD, Sutton GP, Baenziger JC: Urine GABA levels in ovarian cancer patients: elevated GABA in malignancy. Cancer Lett. 2001 Jan 10;162(1):27-30. [PubMed:11121859 ]
- Nisijima K, Ishiguro T: Cerebrospinal fluid levels of monoamine metabolites and gamma-aminobutyric acid in neuroleptic malignant syndrome. J Psychiatr Res. 1995 May-Jun;29(3):233-44. [PubMed:7473299 ]
- Chebib M, Johnston GA: The 'ABC' of GABA receptors: a brief review. Clin Exp Pharmacol Physiol. 1999 Nov;26(11):937-40. [PubMed:10561820 ]
- Petroff OA: GABA and glutamate in the human brain. Neuroscientist. 2002 Dec;8(6):562-73. doi: 10.1177/1073858402238515. [PubMed:12467378 ]
- Pearl PL, Hartka TR, Cabalza JL, Taylor J, Gibson MK: Inherited disorders of GABA metabolism. Future Neurol. 2006 Sep;1(5):631-636. doi: 10.2217/14796708.1.5.631. [PubMed:23842532 ]
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