page_title: Glutamate decarboxylase
section_title: Stiff person syndrome
hierarchical_section_title: Glutamate decarboxylase / Role in pathology / Stiff person syndrome
caption_attribution_description: English: Healthy human cerebellum, Purkinje cell layer, t = 36 weeks after rituximab treatment stained with a reference anti-GAD65 monoclonal antibody. Thin arrows show presynaptic terminals staining only with the anti-GAD65 monoclonal antibody
context_page_description: Glutamate decarboxylase or glutamic acid decarboxylase is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO₂. GAD uses PLP as a cofactor. The reaction proceeds as follows:
  HOOC-CH₂-CH₂-CH-COOH → CO₂ + HOOC-CH₂-CH₂-CH₂NH₂
  In mammals, GAD exists in two isoforms with molecular weights of 67 and 65 kDa, which are encoded by two different genes on different chromosomes. 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.
context_section_description: High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker.
caption: Stiff man human cerebellum stained with a reference anti-GAD65 monoclonal antibody. Thin arrows show presynaptic terminals staining only with the anti-GAD65 monoclonal antibody
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