Everything about Glutamic Acid Decarboxylase totally explained
Glutamate decarboxylase (GAD) is an
enzyme that catalyzes the decarboxylation of
glutamate to
GABA and CO
2. GAD uses
PLP as a
cofactor. The reaction proceeds as follows:
HOOC-CH
2-CH
2-CH(NH
2)-COOH → CO
2 + HOOC-CH
2-CH
2-CH
2NH
2
In mammals, GAD exists in two
isoforms encoded by two different
genes -
Gad1 and
Gad2. These isoforms are GAD
67 and GAD
65 with molecular weights of 67 and 65
kDa, respectively. GAD1 and GAD2 are expressed in the brain where GABA is used as a
neurotransmitter, GAD2 is also expressed in the pancreas.
Role in pathology
Diabetes
Both GAD
67 and GAD
65 are targets of autoantibodies in people who later develop insulin-dependent
diabetes mellitus. Injections with GAD
65 has been shown to preserve some insulin production for 30 months in humans with type 1 diabetes.
Schizophrenia and Bipolar disorder
Substantial dysregulation of GAD mRNA expression, coupled with downregulation of
reelin, is observed in
schizophrenia and
bipolar disorder. The most pronounced downregulation of GAD67 was found in hippocampal
stratum oriens layer in both disorders and in other layers and structures of hippocampus with varying degrees.
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