gammaaminobutírico

Gamma-aminobutírico, commonly known as GABA, is the primary inhibitory neurotransmitter of the mammalian central nervous system. It is a non-protein amino acid synthesized from glutamate by the enzyme glutamate decarboxylase (GAD) with the vitamin B6 derivative pyridoxal phosphate as a cofactor. GABA is found throughout the brain and spinal cord and plays a key role in regulating neuronal excitability.

GABA exerts its effects through three main receptor types. The ionotropic receptors GABA-A and GABA-C (also called GABA-A rho) are ligand-gated chloride channels that, when activated, typically cause hyperpolarization and inhibition of neuronal firing. The metabotropic receptor GABA-B is G-protein-coupled and modulates ion channels and second messenger pathways, contributing to slower, longer-lasting inhibitory effects. Signaling can be phasic at synapses or tonic via extrasynaptic receptors, helping to shape network activity.

Removal and metabolism of GABA in the synaptic cleft occur mainly through reuptake by GABA transporters (GAT-1, GAT-2, GAT-3). Inside cells, GABA is degraded by GABA transaminase (GABA-T) to succinic semialdehyde, which is further converted to succinate and enters the tricarboxylic acid cycle; an alternative route links GABA metabolism to the glutamate–GABA cycle.

Clinical and pharmacological relevance includes associations with epilepsy, anxiety disorders, sleep regulation, and certain movement disorders. Drugs that modulate the GABA system include benzodiazepines and barbiturates (positive allosteric modulators of GABA-A receptors), vigabatrin (GABA-T inhibitor), valproate, and various anticonvulsants and sedatives. Some medications, such as gabapentin and pregabalin, increase GABAergic activity indirectly, and alcohol can enhance GABA receptor function.