Glutamate decarboxylase

Overview
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 2 NH 2

In mammals, GAD exists in two isoforms encoded by two different genes - Gad1 and Gad2. These isoforms are GAD67 and GAD65 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.

Diabetes
Both GAD67 and GAD65 are targets of autoantibodies in people who later develop insulin-dependent diabetes mellitus. Injections with GAD65 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.