Gamma-aminobutyric acid
You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.
| Gamma-aminobutyric acid | |
|---|---|
| |
| |
| IUPAC name | 4-aminobutanoic acid |
| Identifiers | |
| CAS number | |
| PubChem | |
| MeSH | |
| SMILES | C(CC(=O)O)CN |
| Properties | |
| Molecular formula | C4H9NO2 |
| Molar mass | 103.12 g/mol |
| Melting point |
203°C |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references | |
Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
Overview
Gamma-aminobutyric acid (usually abbreviated to GABA) is an inhibitory neurotransmitter found in the nervous systems of widely-divergent species. It is the chief inhibitory neurotransmitter in the central nervous system and also in the retina. GABA is an amino acid, but is not found in proteins. Although some GABA can be found in pancreatic islet cells and kidney, there are no significant amounts of GABA in mammalian tissues other than the tissues of the nervous system.
Function
In vertebrates, GABA acts at inhibitory synapses in the brain. GABA 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 the flow of either negatively-charged chloride ions into the cell or positively-charged potassium ions out of the cell. This action results in a negative change in the transmembrane potential, usually causing hyperpolarization. Three general classes of GABA receptor are known: GABAA and GABAC ionotropic receptors, which are ion channels themselves, and GABAB metabotropic receptors, which are G protein-coupled receptors that open ion channels via intermediaries (G proteins).
Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate. Medium Spiny Cells are a typical example of inhibitory CNS GABAergic cells. GABA exhibits excitatory actions in insects, mediating muscle activation at synapses between nerves and muscle cells, and also the stimulation of certain glands. In hippocampus and neocortex of the mammalian brain, GABA has primarily excitatory effects early in development, and is in fact the major excitatory neurotransmitter in many regions of the brain prior to the maturation of glutamate synapses - See developing cortex. Whether GABA is excitatory or inhibitory depends on the direction (into or out of the cell) and magnitude of the ionic currents controlled by the GABAA receptor. When net positive ionic current is directed into the cell, GABA is excitatory, when the net positive current is directed out of the cell, GABA is inhibitory. A developmental switch in the molecular machinery controlling the polarity of this current is responsible for the changes in the functional role of GABA between the neonatal and adult stages.
In spastic cerebral palsy in humans, GABA cannot be absorbed properly by the damaged nerve rootlets leading to certain muscles; this leads to hypertonia in those muscles.
Structure and conformation
GABA is found mostly as a zwitterion, that is, with the carboxyl group deprotonated and the amino group protonated. Its conformation depends on its environment. In the gas phase, a highly folded conformation is strongly favored due to the electrostatic attraction between the two functional groups. The stabilization is about 50 kcal/mol, according to quantum chemistry calculations. In the solid state, a more extended conformation is found, with a trans conformation at the amino end and a gauche conformation at the carboxyl end. This is due to the packing interactions with the neighboring molecules. In solution, five different conformations, some folded and some extended are found as a result of solvation effects. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. Many GABA analogues with pharmaceutical applications have more rigid structures in order to control the binding better.[1][1]
History
Gamma-aminobutyric acid was first synthesized in 1883, and was first known only as a plant and microbe metabolic product. In 1950, however, GABA was discovered to be an integral part of the mammalian central nervous system.[1]
Synthesis
Organisms synthesize GABA from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate as a cofactor. It is worth noting that this process converts the principal excitatory neurotransmitter (glutamate) into the principal inhibitory one (GABA).
Pharmacology
Drugs that act as agonists of GABA receptors (known as GABA analogues or GABAnergic drugs) or increase the available amount of GABA typically have relaxing, anti-anxiety and anti-convulsive effects. Many of the substances below are known to cause anterograde amnesia and retrograde amnesia.
GABA has been purported to increase the amount of the Human Growth Hormone. The results of those studies have been seldom replicated, and have recently been in question since it is unknown whether GABA can pass the blood-brain barrier.
Drugs that affect GABA receptors:
- avermectins—doramectin, selamectin, ivermectin
- barbiturates
- bicucullines - GABA antagonist
- benzodiazepines
- baclofen
- baicalin and baicalein from skullcap scutellaria lateriflora
- carbamazepines[1]
- cyclopyrrolone derivatives such as zopiclone
- fluoroquinolones
- gabazine (SR-95531)
- gamma-Hydroxybutyric acid (GHB)[1]
- gamma-amino-beta-hydroxybutyric acid
- imidazopyridine derivatives such as zolpidem
- kavalactones[1]
- muscimol
- phenytoin
- picamilon
- picrotoxin
- progabide
- propofol
- phenibut
- pyrazolopyrimidine derivatives such as zaleplon
- thujone—GABA antagonist
Drugs that affect GABA in other ways:
- tiagabine—potentiates by inhibiting uptake into neurons and glia
- vigabatrin—potentiates by inhibiting GABA-T, preventing GABA breakdown
- valproate—potentiates by inhibiting GABA-T
- tetanospasmin—primary toxin of tetanus bacteria, blocks release of GABA
- hyperforin—inhibits the reuptake of GABA
See also
References
External links
da:GABA
de:Γ-Aminobuttersäurefr:Acide gamma-aminobutyrique
it:Acido gamma-amminobutirrico
he:GABA
hu:Gamma-amino-vajsav
nl:Gamma-aminoboterzuur
ja:Γ-アミノ酪酸
no:GABAsl:Γ-aminomaslena kislina
fi:Gamma-aminovoihappo
sv:GABAuk:Гамма-аміномасляна кислота
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
