Glutamate decarboxylase

protein
Name = Glutamic acid decarboxylase 1
caption =


width =
HGNCid = 4092
Symbol = GAD1
AltSymbols = GLUTAMATE DECARBOXYLASE, BRAIN, 67-KD; GAD67
EntrezGene = 2571
OMIM = 605363
RefSeq =
UniProt = Q99259
PDB =
ECnumber = 4.1.1.15
Chromosome = 2
Arm = q
Band = 31
LocusSupplementaryData = protein
Name = glutamic acid decarboxylase 2
caption =


width =
HGNCid = 11284
Symbol = GAD2
AltSymbols = GAD65
EntrezGene = 2572
OMIM = 4093
RefSeq =
UniProt = Q05329
PDB = 1ES0
ECnumber = 4.1.1.15
Chromosome = 10
Arm = p
Band = 11.23
LocusSupplementaryData =

Glutamate decarboxylase (GAD) 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(NH₂)-COOH → CO₂ + HOOC-CH₂-CH₂-CH₂NH₂

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.cite journal | author = Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ | title = Two genes encode distinct glutamate decarboxylases | journal = Neuron | volume = 7 | issue = 1 | pages = 91–100 | year = 1991 | pmid = 2069816 | doi = 10.1016/0896-6273(91)90077-D ] 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.cite journal | author = Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, De Camilli P, Camilli PD | title = Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase | journal = Nature | volume = 347 | issue = 6289 | pages = 151–6 | year = 1990 | pmid = 1697648 | doi = 10.1038/347151a0 ] cite journal | author = Kaufman DL, Erlander MG, Clare-Salzler M, Atkinson MA, Maclaren NK, Tobin AJ | title = Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus | journal = J. Clin. Invest. | volume = 89 | issue = 1 | pages = 283–92 | year = 1992 | pmid = 1370298 | doi = 10.1172/JCI115573| url = http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=1370298] Injections with GAD₆₅ has been shown to preserve some insulin production for 30 months in humans with type 1 diabetes. [ [http://www.diamyd.se/docs/PressClip.aspx?PageID=4&LangID=2&ClipID=420&sm=b_b Diamyd press release] ]

chizophrenia and Bipolar disorder

Substantial dysregulation of GAD mRNA expression, coupled with downregulation of reelin, is observed in schizophrenia and bipolar disorder.cite journal | author = Woo TU, Walsh JP, Benes FM | title = 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 | journal = Arch. Gen. Psychiatry | volume = 61 | issue = 7 | pages = 649–57 | year = 2004 | pmid = 15237077 | doi = 10.1001/archpsyc.61.7.649 ] 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.cite journal | author = Benes FM, Lim B, Matzilevich D, Walsh JP, Subburaju S, Minns M | title = Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 24 | pages = 10164–9 | year = 2007 | pmid = 17553960 | doi = 10.1073/pnas.0703806104 ]

References

External links

* [http://www.schizophreniaforum.org/new/detail.asp?id=1358 Genetics, Expression Profiling Support GABA Deficits in Schizophrenia] - Schizophrenia Research Forum, 25 June 2007.