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Glutamic Acid Decarboxylase (GAD65 and GAD67) Antibodies
g-Aminobutyric acid (GABA) is the major
known inhibitory neurotransmitter. The rate-limiting step in the synthesis of
GABA is the decarboxylation of glutamate by glutamate decarboxylase (GAD;
L-glutamate 1-carboxy-lyase, EC 4.1.115). In the CNS GAB is entirely restricted
to GABAergic neurons. GAD is also present in the b-cells of the pancreas and
autoantibodies to various GAD polypeptides are detected in insulin-dependent
diabetes mellitus. Cloning of GAD genes have identified two subtypes:
GAD65 (65 kDa; human 585
AA chromosome 10) and GAD67
(67 kDa; human 594 AA, chromosome 2) share approx. 65% amino acid homology. The
N-terminus is the most divergent while the C-terminus is highly conserved.
Although both GAD isoforms catalyzes the conversion of GABA but interact
differently with the co-factor pyridoxal 5'-phosphate suggesting their
activities are differentially regulated. GAD67 is cytosolic, while GAD65 is
membrane associated. GAD65 is a major autoantigen in diabetes mellitus and
stiff-man syndrome, a rare disease of the brain. ADI has produced antibodies to
GAD65 and GAD67 using peptide sequences specific to each subtype.
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