4-aminobutyrate transaminase

Enzyme involved in the metabolism of gamma-aminobutyric acid

4-aminobutyrate transaminase (also known as GABA transaminase) is an enzyme that plays a crucial role in the metabolism of the neurotransmitter gamma-aminobutyric acid (GABA). This enzyme is responsible for the conversion of GABA into succinic semialdehyde, which is a key step in the GABA shunt, a metabolic pathway that links the metabolism of GABA with the tricarboxylic acid cycle.

Structure

4-aminobutyrate transaminase is a pyridoxal phosphate-dependent enzyme, meaning it requires this cofactor to function. The enzyme is typically a homodimer, with each subunit contributing to the active site. The structure of 4-aminobutyrate transaminase has been elucidated through X-ray crystallography, providing insights into its catalytic mechanism and substrate specificity.

Function

The primary function of 4-aminobutyrate transaminase is to catalyze the transamination reaction between GABA and alpha-ketoglutarate, producing succinic semialdehyde and glutamate. This reaction is a part of the GABA shunt, which serves to recycle GABA and integrate it into central metabolic pathways. The GABA shunt is particularly important in the central nervous system, where GABA acts as a major inhibitory neurotransmitter.

Clinical significance

Deficiencies or malfunctions in 4-aminobutyrate transaminase can lead to disorders such as GABA-transaminase deficiency, which is characterized by elevated levels of GABA in the brain and associated neurological symptoms. Inhibitors of this enzyme, such as vigabatrin, are used in the treatment of certain types of epilepsy, as they increase the levels of GABA in the brain by preventing its breakdown.

Related pages

• Gamma-aminobutyric acid
• Pyridoxal phosphate
• Tricarboxylic acid cycle
• Vigabatrin

Gallery

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  Structure of 4-aminobutyrate transaminase