View source for Glutamate decarboxylase

{{protein
| Name = [[GAD1|Glutamic acid decarboxylase 1]]
| caption = 
| image = 
| 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 = [[GAD2|glutamic acid decarboxylase 2]]
| caption = 
| image = 
| width = 
| HGNCid = 11284
| Symbol = [[GAD2]]
| AltSymbols = 
| EntrezGene = 2572
| OMIM = 4093
| RefSeq =
| UniProt = Q05329
| PDB = 1ES0
| ECnumber = 4.1.1.15
| Chromosome = 10
| Arm = p
| Band = 11.23
| LocusSupplementaryData = 
}}

{{SI}}


==Overview==
'''Glutamate decarboxylase''' (GAD) is an [[enzyme]] that catalyzes the decarboxylation of [[glutamate]] to [[GABA]] and CO<sub >2</sub >. GAD uses [[Pyridoxal-phosphate|PLP]] as a [[cofactor]]. The reaction proceeds as follows:

HOOC-CH<sub >2</sub >-CH<sub >2</sub >-CH(NH<sub >2</sub >)-COOH → CO<sub >2</sub > + HOOC-CH<sub >2</sub >-CH<sub >2</sub >-CH<sub >2</sub >NH<sub >2</sub >

In mammals, GAD exists in two [[isoform]]s encoded by two different [[gene]]s - ''Gad1'' and ''Gad2''. These isoforms are GAD<sub>67</sub> and GAD<sub>65</sub> with molecular weights of 67 and 65 [[kDa]], respectively.<ref name="pmid2069816">{{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 | issn = }}</ref> 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<sub>67</sub> and GAD<sub>65</sub> are targets of autoantibodies in people who later develop insulin-dependent [[diabetes mellitus]].<ref name="pmid1697648">{{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 | issn = }}</ref> <ref name="pmid1370298">{{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 = | issn = | url = http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=1370298}}</ref> Injections with GAD<sub>65</sub> has been shown to preserve some insulin production for 30 months in humans with type 1 diabetes.<ref>[http://www.diamyd.se/docs/PressClip.aspx?PageID=4&LangID=2&ClipID=420&sm=b_b Diamyd press release]</ref>

===Schizophrenia and Bipolar disorder===
Substantial dysregulation of GAD mRNA expression, coupled with downregulation of [[reelin]], is observed in [[schizophrenia]] and [[bipolar disorder]].<ref name="pmid15237077">{{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 | issn = }}</ref> 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.<ref name="pmid17553960">{{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 | issn = }}</ref>

== References ==
{{Reflist|2}}

== 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.

[[Category:EC 4.1.1]]
[[Category:Molecular neuroscience]]

{{Carbon-carbon lyases}}
{{Amino acid metabolism enzymes}}


[[ru:Глутаматдекарбоксилаза]]
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