Gamma-aminobutyric acid metabolic enzymes

Gamma-aminobutyric acid (GABA) metabolic enzymes are a group of proteins responsible for the synthesis and degradation of GABA, the primary inhibitory neurotransmitter in the central nervous system [1]. The primary enzymes include glutamate decarboxylase (GAD), which catalyzes the conversion of glutamate to GABA, and 4-aminobutyrate aminotransferase (GABA transaminase or GABA-T), which degrades GABA into succinic semialdehyde [2, 3]. These enzymes constitute the "GABA shunt," a metabolic pathway that regulates GABA levels and maintains the balance between neuronal excitation and inhibition [1]. Dysregulation of these enzymes is linked to neurological disorders such as epilepsy, where insufficient GABA levels lead to hyperexcitability, and rare metabolic conditions like GABA transaminase deficiency [5]. Pharmacological modulation of these enzymes is a key therapeutic strategy; for example, vigabatrin is an irreversible inhibitor of GABA-T used to increase GABA concentrations in patients with refractory seizures [4]. However, targeting these enzymes can lead to significant side effects, such as the permanent visual field defects associated with long-term vigabatrin use [4].

Other names

GABA metabolic enzymesGABA shunt enzymesGABA-metabolizing enzymes

Inhibition of GABA degradation via GABA transaminase (GABA-T) blockade or modulation of GABA synthesis via glutamate decarboxylase (GAD) activity [1, 4].