Glutamate decarboxylase

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide (CO₂). GAD uses pyridoxal-phosphate (PLP) as a cofactor. The reaction proceeds as follows:

HOOC−CH₂−CH₂−CH(NH₂)−COOH → CO₂ + HOOC−CH₂−CH₂−CH₂NH₂

In mammals, GAD exists in two isoforms with molecular weights of 67 and 65 kDa (GAD₆₇ and GAD₆₅), which are encoded by two different genes on different chromosomes (GAD1 and GAD2 genes, chromosomes 2 and 10 in humans, respectively). GAD₆₇ and GAD₆₅ are expressed in the brain where GABA is used as a neurotransmitter, and they are also expressed in the insulin-producing β-cells of the pancreas, in varying ratios depending upon the species. Together, these two enzymes maintain the major physiological supply of GABA in mammals, though it may also be synthesized from putrescine in the enteric nervous system, brain, and elsewhere by the actions of diamine oxidase and aldehyde dehydrogenase 1a1.

Several truncated transcripts and polypeptides of GAD₆₇ are detectable in the developing brain, however their function, if any, is unknown.