Gamma-Aminobutyric acid

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Gamma-Aminobutyric acid
2D structure for Gamma-Aminobutyric acid
Chemical Name	4-amino-Butanoic acid
Chemical Formula	C₄H₉NO₂
CAS Number	56-12-2
Chemical Information	HMDB00112
Biochemical Taxonomy	Amino Acids
Functional Taxonomy	Not Available
Nutritional Taxonomy	Not Available
Metabolic Pathways	Bile Acid Biosynthesis Fatty Acid Metabolism Glycerolipid Metabolism Glycolysis Pyruvate Metabolism
Biofluid Location	Blood Cerebrospinal Fluid (CSF) Saliva Urine
Tissue Location	Brain Epidermis Fibroblasts Hippocampus Kidney Muscle Nerve Cells Neuron Neurons Spleen Testis Adrenal Cortex
Normal Biofluid Concentrations	Blood: 0.110 +/- 0.23 uM Cerebrospinal Fluid (CSF): 0.093 (0.083-0.10) uM Cerebrospinal Fluid (CSF): 0.23 +/- 0.075 uM Cerebrospinal Fluid (CSF): 0.32 (0.2 -0.45) uM Saliva: >10 uM Urine: 0.17 +/- 0.025 umol/mmol creatinine Urine: 1.3 (0.0-2.8) umol/mmol creatinine Urine: <0.461 umol/mmol creatinine
Normal Tissue Concentrations	Not Available
Diseases / Conditions Related to Nutrition	Aseptic meningitis Children with febrile convulsions Epilepsy Epilepsy treated with Vigabatrin Epileptic children on valproate treatment Probable Alzheimer's Disease Tuberculous meningitis Untreated epileptic children
Other (Monogenic Disorders)	Not Available
Abnormal Biofluid Concentrations	Blood (Probable Alzheimer's Disease): 1.84 +/- 0.215 uM Cerebrospinal Fluid (CSF) (Aseptic meningitis): 0.00013 +/- 0.00002 uM Cerebrospinal Fluid (CSF) (Children with febrile convulsions): 0.1 (0.063 - 0.179) uM Cerebrospinal Fluid (CSF) (Epilepsy treated with Vigabatrin): 4.0 +/- 4.2 uM Cerebrospinal Fluid (CSF) (Epilepsy): 1.5 +/- 1.1 uM Cerebrospinal Fluid (CSF) (Epileptic children on valproate treatment): 0.52 - 0.57 uM Cerebrospinal Fluid (CSF) (Tuberculous meningitis): 0.0002 +/- 0.000013 uM Cerebrospinal Fluid (CSF) (Untreated epileptic children): 0.11 (0.067 - 0.176) uM
Abnormal Tissue Concentrations	Not Available
Physiological Processes	Not Available

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Introduction

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Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter found in the nervous systems of widely divergent species. It is the chief inhibitory neurotransmitter in the vertebrate central nervous system. 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 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. These include 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 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. GABA has also 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. 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 analogues or GABAergic drugs) or increase the available amount of GABA typically have relaxing, anti-anxiety and anti-convulsive effects. (http://en.wikipedia.org/wiki/GABA) Doses of GABA 1 to 3 g orally also have been used effectively to raise the IQ of mentally retarded persons. GABA is found to be deficient in cerebrospinal fluid and 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, e.g., 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 also are useful in lowering hypertension. Three grams orally have been effective in control of 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 deficiency of GABA; GABA has many promising uses in therapy. Cerebrospinal fluid levels of GABA may be useful in diagnosing very serious diseases. Vitamin B6, manganese, taurine and lysine can increase both GABA synthesis and effects, while aspartic acid and glutamic acid probably inhibit GABA effects. (http://www.dcnutrition.com/AminoAcids/Detail.CFM)The brain's principal inhibitory neurotransmitter, GABA, along with serotonin and norepinephrine, is one of several neurotransmitters that appear to be involved in the pathogenesis of anxiety and mood disorders. There are two principal subtypes of postsynaptic GABA receptor complexes, the GABA-A and GABA-B receptor complexes. 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; activation of the receptor induces increased inward chloride ion flux, resulting in membrane hyperpolarization and neuronal inhibition. 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 membrane transporter proteins, known as 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. 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. In support of the anticonvulsant and anxiolytic effects of the GABA-A receptor are findings that GABA-A antagonists produce convulsions in animals and the demonstration that there is decreased GABA-A receptor binding in a positron emission tomography (PET) study of patients with panic disorder. Low plasma GABA has been reported in some depressed patients and, in fact, may be a useful trait marker for mood disorders. (The Role Of GABA In The Pathogenesis And Treatment Of Anxiety And Other Neuropsychiatric Disorders: http://www.vcu-cme.org/gaba/overview.html)