T3DB: Gamma-Aminobutyric acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (10)XML

Targets (10)

Record Information

Version

2.0

Creation Date

2014-08-29 06:03:38 UTC

Update Date

2018-03-21 17:46:11 UTC

Accession Number

T3D4250

Identification

Common Name

Gamma-Aminobutyric acid

Class

Small Molecule

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 anticonvulsive 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.

Compound Type

Amine
Animal Toxin
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
3-Carboxypropylamine
4-Aminobutanoate
4-Aminobutanoic acid
4-Aminobutyrate
4-Aminobutyric acid
Aminalon
g-Aminobutyrate
g-Aminobutyric acid
GABA
Gaballon
Gamarex
gamma Aminobutyrate
gamma Aminobutyric acid
gamma-Aminobutyrate
gamma-Aminobutyric acid
Gammalon
Gammalone
Gammar
Gammasol
Mielogen
Mielomade
Omega-Aminobutyrate
Omega-Aminobutyric acid
Piperidate
Piperidic acid
Piperidinate
Piperidinic acid
w-Aminobutyrate
w-Aminobutyric acid
γ-Aminobutyrate
γ-Aminobutyric acid

Chemical Formula

C₄H₉NO₂

Average Molecular Mass

103.120 g/mol

Monoisotopic Mass

103.063 g/mol

CAS Registry Number

56-12-2

IUPAC Name

4-aminobutanoic acid

Traditional Name

gamma(amino)-butyric acid

SMILES

NCCCC(O)=O

InChI Identifier

InChI=1S/C4H9NO2/c5-3-1-2-4(6)7/h1-3,5H2,(H,6,7)

InChI Key

InChIKey=BTCSSZJGUNDROE-UHFFFAOYSA-N

Chemical Taxonomy

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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Gamma amino acids and derivatives

Alternative Parents

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

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

monocarboxylic acid (CHEBI:16865 )
gamma-amino acid (CHEBI:16865 )
Amino fatty acids (C00334 )
Other amino acids (C00334 )
Biogenic amines (C00334 )
Amino fatty acids (LMFA01100039 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Extracellular
Lysosome
Membrane
Mitochondria

Biofluid Locations

Not Available

Tissue Locations

Adrenal Cortex
Brain
Epidermis
Fibroblasts
Hippocampus
Kidney
Muscle
Nerve Cells
Neuron
Spleen
Testes

Pathways

Name	SMPDB Link	KEGG Link
Glutamate Metabolism	SMP00072	map00250
2-Hydroxyglutric Aciduria (D And L Form)	SMP00136	Not Available
4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency	SMP00243	Not Available
GABA-Transaminase Deficiency	SMP00351	Not Available
Homocarnosinosis	SMP00385	Not Available
Succinic semialdehyde dehydrogenase deficiency	SMP00567	Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	203°C
Boiling Point	Not Available
Solubility	1300.0 mg/mL
LogP	-3.17

Predicted Properties

Property	Value	Source
Water Solubility	365 g/L	ALOGPS
logP	-3	ALOGPS
logP	-2.9	ChemAxon
logS	0.55	ALOGPS
pKa (Strongest Acidic)	4.53	ChemAxon
pKa (Strongest Basic)	10.22	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	63.32 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	25.46 m³·mol⁻¹	ChemAxon
Polarizability	10.62 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00dj-1900000000-f831f79dfcaeffa8b177	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00di-1900000000-2de9d92a2cfc7bc655f4	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00di-1900000000-73bbf2ee0803f058dbed	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00di-1901000000-85d4bd98af8534428b5a	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00di-0900000000-6be23968e972a414be51	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-00di-1900000000-9a224763afd8ca892add	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00di-9800000000-d8906d09ca1872a6391c	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-0udi-1900000000-54db7e21790401045519	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (3 TMS)	splash10-00di-1901000000-b047af158215c2b5b8e8	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-001i-9000000000-21ea76dfb0da62031f1d	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-00di-0901000000-5d60b0a446fd8122f613	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00dj-1900000000-f831f79dfcaeffa8b177	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-1900000000-2de9d92a2cfc7bc655f4	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-1900000000-73bbf2ee0803f058dbed	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-1901000000-85d4bd98af8534428b5a	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-0900000000-6be23968e972a414be51	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-1900000000-9a224763afd8ca892add	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-9800000000-d8906d09ca1872a6391c	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0udi-1900000000-54db7e21790401045519	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-00di-1901000000-b047af158215c2b5b8e8	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00dj-1900000000-1219470a0be188da64e6	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0900000000-f7117dfaf9d856c95919	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0006-1900000000-e35585a985d8128d044e	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-9000000000-d5f55a414ff1e8c65d9d	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0fk9-9700000000-4b2809309587240dd479	2017-10-06	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-0uxr-8900000000-ce0d8f44422836cd9965	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0005-9000000000-8ce5afb97d7c08821da3	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-0005-9100000000-32c433b2c916697690f8	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0udi-0900000000-5831aaabdf53f3132ae5	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0a4i-9000000000-9babfd4a6937ecba7318	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0a4i-9000000000-e1c0c1485d846e9b123b	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0udi-0900000000-647d55ecf98850e7a875	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0udi-0900000000-7c107641a38922c88fca	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-9000000000-86718b349efad6334e3a	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-9000000000-a1e84e55e4b6c6628d5d	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0006-0009000000-29c22bf0ed844d09c0af	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-0udi-0900000000-1d00adad47e42c60c340	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-0udi-1900000000-47b195fb74720cc99464	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-001i-9000000000-a14a52dc59bf9988bb44	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-0udi-5900000000-20c55b2809389d5ad83b	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-000i-9000000000-eca4c5aefca98751a11e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-014j-9000000000-f0783316e09291749409	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-0005-9000000000-81837eb9c0b926cb0e81	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-0005-9000000000-8b48126992d7fa242636	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-000i-9000000000-7d4636efbc4e5d75872e	2012-08-31	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-9100000000-655f9d93a35bfa537583	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00ku-9000000000-4a334d5e272576f62403	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-4a13b03446b3370ccd43	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-9100000000-655f9d93a35bfa537583	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00ku-9000000000-4a334d5e272576f62403	2015-05-27	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-001i-9000000000-dbf4f9e19a35f953a189	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 125 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 90 MHz, D₂O, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 25.16 MHz, D₂O, experimental)	Not Available	2014-09-23	View Spectrum
1D NMR	¹H NMR Spectrum (1D, D₂O, experimental)	Not Available	2016-10-22	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

Minimum Risk Level

Not Available

Health Effects

Chronically high levels of GABA are associated with at least 5 inborn errors of metabolism including: D-2-Hydroxyglutaric Aciduria, 4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency, GABA-Transaminase Deficiency, Homocarnosinosis and Succinic semialdehyde dehydrogenase deficiency.

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

16865

BioCyc ID

4-AMINO-BUTYRATE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

ABU

ACToR ID

Not Available

Wikipedia Link

GABA

References

Synthesis Reference

Not Available

MSDS

T3D4250.pdf

General References

Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. [12097436 ]
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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [7473299 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Glycine amidinotransferase, mitochondrial

General Function:: Glycine amidinotransferase activity
Specific Function:: Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis.
Gene Name:: GATM
Uniprot ID:: P50440
Molecular Weight:: 48455.01 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

Target Details

2. Gamma-aminobutyric acid receptor subunit alpha-1

General Function:: Inhibitory extracellular ligand-gated ion channel activity
Specific Function:: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:: GABRA1
Uniprot ID:: P14867
Molecular Weight:: 51801.395 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.02137 uM	Not Available	BindingDB 24183
Inhibitory	0.05754 uM	Not Available	BindingDB 24183
Inhibitory	0.07762 uM	Not Available	BindingDB 24183

References

Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]

Target Details

3. Gamma-aminobutyric acid receptor subunit alpha-3

General Function:: Inhibitory extracellular ligand-gated ion channel activity
Specific Function:: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:: GABRA3
Uniprot ID:: P34903
Molecular Weight:: 55164.055 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.05011 uM	Not Available	BindingDB 24183

References

Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]

Target Details

4. Gamma-aminobutyric acid receptor subunit alpha-6

General Function:: Inhibitory extracellular ligand-gated ion channel activity
Specific Function:: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:: GABRA6
Uniprot ID:: Q16445
Molecular Weight:: 51023.69 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.07762 uM	Not Available	BindingDB 24183

References

Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]

Target Details

5. Gamma-aminobutyric acid receptor subunit rho-3

General Function:: Gaba-a receptor activity
Specific Function:: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:: GABRR3
Uniprot ID:: A8MPY1
Molecular Weight:: 54271.1 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.58 uM	Not Available	BindingDB 24183

References

Chang Y, Covey DF, Weiss DS: Correlation of the apparent affinities and efficacies of gamma-aminobutyric acid(C) receptor agonists. Mol Pharmacol. 2000 Dec;58(6):1375-80. [11093776 ]

Target Details

6. Gamma-aminobutyric acid type B receptor subunit 2

General Function:: G-protein coupled gaba receptor activity
Specific Function:: Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.
Gene Name:: GABBR2
Uniprot ID:: O75899
Molecular Weight:: 105820.52 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.025 uM	Not Available	BindingDB 24183

References

Froestl W, Mickel SJ, Hall RG, von Sprecher G, Strub D, Baumann PA, Brugger F, Gentsch C, Jaekel J, Olpe HR, et al.: Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists. J Med Chem. 1995 Aug 18;38(17):3297-312. [7650684 ]

Target Details

7. Proton-coupled amino acid transporter 1

General Function:: L-proline transmembrane transporter activity
Specific Function:: Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recognize their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid (By similarity).
Gene Name:: SLC36A1
Uniprot ID:: Q7Z2H8
Molecular Weight:: 53075.045 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	4000 uM	Not Available	BindingDB 24183

References

Thondorf I, Voigt V, Schafer S, Gebauer S, Zebisch K, Laug L, Brandsch M: Three-dimensional quantitative structure-activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1). Bioorg Med Chem. 2011 Nov 1;19(21):6409-18. doi: 10.1016/j.bmc.2011.08.058. Epub 2011 Sep 5. [21955456 ]

Target Details

8. Sodium- and chloride-dependent GABA transporter 1

General Function:: Neurotransmitter:sodium symporter activity
Specific Function:: Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:: SLC6A1
Uniprot ID:: P30531
Molecular Weight:: 67073.0 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	5 uM	Not Available	BindingDB 24183

References

Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]

Target Details

9. Sodium- and chloride-dependent GABA transporter 3

General Function:: Neurotransmitter:sodium symporter activity
Specific Function:: Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:: SLC6A11
Uniprot ID:: P48066
Molecular Weight:: 70605.145 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	7 uM	Not Available	BindingDB 24183

References

Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]

Target Details

10. Sodium- and chloride-dependent betaine transporter

General Function:: Neurotransmitter:sodium symporter activity
Specific Function:: Transports betaine and GABA. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation.
Gene Name:: SLC6A12
Uniprot ID:: P48065
Molecular Weight:: 69367.655 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	36 uM	Not Available	BindingDB 24183

References

Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]

Gamma-Aminobutyric acid (T3D4250)

Structure for T3D4250: Gamma-Aminobutyric acid

Targets

References

Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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