From Wikipedia, the free encyclopedia
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.[1] GAD1 and GAD2 are expressed in the brain where GABA is used as a neurotransmitter, GAD2 is also expressed in the pancreas.
[edit] Role in pathology
[edit] Diabetes
Both GAD67 and GAD65 are targets of autoantibodies in people who later develop insulin-dependent diabetes mellitus.[2] [3] Injections with GAD65 has been shown to preserve some insulin production for 30 months in humans with type 1 diabetes.[4]
[edit] Schizophrenia and Bipolar disorder
Substantial dysregulation of GAD mRNA expression, coupled with downregulation of reelin, is observed in schizophrenia and bipolar disorder.[5] 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.[6]
[edit] References
- ^ Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ (1991). "Two genes encode distinct glutamate decarboxylases". Neuron 7 (1): 91–100. doi:10.1016/0896-6273(91)90077-D. PMID 2069816.
- ^ Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, De Camilli P, Camilli PD (1990). "Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase". Nature 347 (6289): 151–6. doi:10.1038/347151a0. PMID 1697648.
- ^ Kaufman DL, Erlander MG, Clare-Salzler M, Atkinson MA, Maclaren NK, Tobin AJ (1992). "Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus". J. Clin. Invest. 89 (1): 283–92. doi:10.1172/JCI115573. PMID 1370298.
- ^ Diamyd press release
- ^ Woo TU, Walsh JP, Benes FM (2004). "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". Arch. Gen. Psychiatry 61 (7): 649–57. doi:10.1001/archpsyc.61.7.649. PMID 15237077.
- ^ Benes FM, Lim B, Matzilevich D, Walsh JP, Subburaju S, Minns M (2007). "Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars". Proc. Natl. Acad. Sci. U.S.A. 104 (24): 10164–9. doi:10.1073/pnas.0703806104. PMID 17553960.
[edit] External links
