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Glutamate decarboxylase

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Glutamate decarboxylase
Symbol(s): GAD1 GAD2
Locus: [[Chromosome__(human)|]]
EC number 4.1.1.15
EntrezGene 24379
OMIM 605363
RefSeq [1]
UniProt Q99259

Glutamate decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to GABA. GAD uses PLP as a cofactor.

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.[1] 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 GAD67 and GAD65 are targets of autoantibodies in people who later develop insulin-dependent diabetes mellitus [2] FT, FT.

Schizophrenia and Bipolar disorder

Substantial dysregulation of GAD mRNA expression is observed in schizophrenia and bipolar disorder.[3]

References

  1. Erlander MG, Tillakaratne NJK, Feldblum S, Patel N, Tobin AJ (1991) Two genes encode distinct glutamate decarboxylases. Neuron 7:91-100. PMID 2069816
  2. Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, De Camilli P. (1990) Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature. 347(6289):151-6. PMID 1697648
  3. Woo TU, Walsh JP, Benes FM. (2004) Arch Gen Psychiatry. 61(7):649-57. Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. PMID 15237077
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