Glutamate decarboxylase 1592325 223698629 2008-07-05T09:27:40Z DOI bot 6652755 Citation maintenance. Removed redundant parameters. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{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 = 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 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 }}</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 }}</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 = 10.1172/JCI115573| 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 }}</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 }}</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]] {{4.1-enzyme-stub}} {{Carbon-carbon lyases}} {{Neurotransmitter metabolism enzymes}} [[ru:Глутаматдекарбоксилаза]] [[sv:Glutaminsyredekarboxylas]]