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street name for lysergic acid diethylamide (同)back breaker, battery-acid, dose, dot, Elvis, loony toons, Lucy in the sky with diamonds, pane, superman, window pane, Zen
any of various water-soluble compounds having a sour taste and capable of turning litmus red and reacting with a base to form a salt
having the characteristics of an acid; "an acid reaction"
any of the enzymes that hydrolize the carboxyl group

PrepTutorEJDIC

酸性の / 酸味のある,すっぱい(sour) / (言葉・態度などが)厳しい,しんらつな / 酸 / すっぱいもの / 《俗》=LSD

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/29 05:02:53」(JST)

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For other uses of the abbreviation "GAD" in medicine, see Gad.

Glutamate decarboxylase or glutamic acid 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.

At least two more forms, GAD₂₅ and GAD₄₄ (embryonic; EGAD) are described in the developing brain. They are coded by the alternative transcripts of GAD1, I-80 and I-86: GAD₂₅ is coded by both, GAD₄₄ - only by I-80.^[2]

Role in pathology

Diabetes

Both GAD₆₇ and GAD₆₅ are targets of autoantibodies in people who later develop type 1 diabetes mellitus or latent autoimmune diabetes.^[3]^[4] Injections with GAD₆₅ has been shown to preserve some insulin production for 30 months in humans with type 1 diabetes.^[5]^[6]

Schizophrenia and bipolar disorder

Substantial dysregulation of GAD mRNA expression, coupled with downregulation of reelin, is observed in schizophrenia and bipolar disorder.^[7] 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.^[8]

Parkinson disease

The bilateral delivery of glutamic acid decarboxylase (GAD) by an adeno-associated viral vector into the subthalamic nucleus of patients between 30 and 75 years of age with advanced, progressive, levodopa-responsive Parkinson disease resulted in significant improvement over baseline during the course of a six-month study.^[9]

Cerebellar disorders

Intracerebellar administration of GAD autoantibodies to animals increase the excitability of motoneurons and impairs the production of nitric oxide (NO), a molecule involved in learning. Epitope recognition contributes to cerebellar involvement.^[10]

Alteration by drugs

Pregabalin, an antiepileptic drug, increases neuronal GABA levels by producing a dose-dependent increase in glutamic acid decarboxylase activity.[1] Extracts from Centella asiatica (gotu kola) and Valeriana officinalis (valerian) stimulated GAD activity.^[11]

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.
^ Szabo G, Katarova Z, Greenspan R (November 1994). "Distinct protein forms are produced from alternatively spliced bicistronic glutamic acid decarboxylase mRNAs during development". Mol. Cell. Biol. 14 (11): 7535–45. PMC 359290. PMID 7935469. //www.ncbi.nlm.nih.gov/pmc/articles/PMC359290/.
^ 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. PMC 442846. PMID 1370298. //www.ncbi.nlm.nih.gov/pmc/articles/PMC442846/.
^ Ludvigsson J, Faresjö M, Hjorth M, Axelsson S, Chéramy M, Pihl M, Vaarala O, Forsander G, Ivarsson S, Johansson C, Lindh A, Nilsson NO, Aman J, Ortqvist E, Zerhouni P, Casas R (October 2008). "GAD treatment and insulin secretion in recent-onset type 1 diabetes". N. Engl. J. Med. 359 (18): 1909–20. doi:10.1056/NEJMoa0804328. PMID 18843118.
^ "Diamyd announces completion of type 1 diabetes vaccine trial with long term efficacy demonstrated at 30 months". Press Release. Diamyd Medical AB. 2008-01-28. http://www.diamyd.com/docs/pressClip.aspx?section=investor&ClipID=420. Retrieved 2010-01-13.
^ 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. PMC 1888575. PMID 17553960. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1888575/.
^ LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Askandar EN, et al (2011). "AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial". Lancet Neurol 10 (4): 309–19. doi:10.1016/S1474-4422(11)70039-4. PMID 21419704.
^ Manto MU, Hampe CS, Rogemond V, Honnorat J. Respective implications of glutamate decarboxylase antibodies in stiff person and cerebellar ataxia. Orphanet J Rare Dis 6:3,2011
^ pmid18066140, F; Schjøtt J (September 2007). "Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system". Canadian Journal of Physiology and Pharmacology 85 (9): 933–42. doi:10.1139/Y07-083. PMID 18066140. http://www.ncbi.nlm.nih.gov/pubmed/18066140.

External links

Media related to Glutamate decarboxylase at Wikimedia Commons
Genetics, Expression Profiling Support GABA Deficits in Schizophrenia - Schizophrenia Research Forum, 25 June 2007.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 1型糖尿病の病因 pathogenesis of type 1 diabetes mellitus
2. 1型糖尿病の予測 prediction of type 1 diabetes mellitus
3. 糖尿病および遺伝的糖尿病症候群の分類 classification of diabetes mellitus and genetic diabetic syndromes
4. スティッフパーソン症候群 stiff person syndrome
5. 成人における小脳性運動失調の概要 overview of cerebellar ataxia in adults

English Journal

Production of gamma-aminobutyric acid from glucose by introduction of synthetic scaffolds between isocitrate dehydrogenase, glutamate synthase and glutamate decarboxylase in recombinant Escherichia coli.

Pham VD1, Lee SH2, Park SJ3, Hong SH4.
Journal of biotechnology.J Biotechnol.2015 Aug 10;207:52-7. doi: 10.1016/j.jbiotec.2015.04.028. Epub 2015 May 18.
Escherichia coli were engineered for the direct production of gamma-aminobutyric acid from glucose by introduction of synthetic protein scaffold. In this study, three enzymes consisting GABA pathway (isocitrate dehydrogenase, glutamate synthase and glutamate decarboxylase) were connected via synthet
PMID 25997833

Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation.

Voytenko LP1, Lushnikova IV2, Savotchenko AV3, Isaeva EV3, Skok MV4, Lykhmus OY4, Patseva MA2, Skibo GG2.
Brain research.Brain Res.2015 Aug 7;1616:134-45. doi: 10.1016/j.brainres.2015.04.061. Epub 2015 May 9.
The hippocampal interneurons are very diverse by chemical profiles and rather inconsistent by sensitivity to CI. Some hippocampal GABAergic interneurons survive certain time after ischemia while ischemia-sensitive interneurons and pyramidal neurons are damaged. GABAergic signaling, nicotinic recepto
PMID 25966616

Deletion of odhA or pyc improves production of γ-aminobutyric acid and its precursor L-glutamate in recombinant Corynebacterium glutamicum.

Wang N1, Ni Y, Shi F.
Biotechnology letters.Biotechnol Lett.2015 Jul;37(7):1473-81. doi: 10.1007/s10529-015-1822-4. Epub 2015 Mar 24.
OBJECTIVES: To enhance γ-aminobutyric acid (GABA) production in recombinant Corynebacterium glutamicum, metabolic engineering strategies were used to improve the supply of the GABA precursor, L-glutamate.RESULTS: C. glutamicum ATCC13032 co-expressing two glutamate decarboxylase genes (gadB1 and gad
PMID 25801673

Japanese Journal

スティフパーソン症候群を有する患者の麻酔経験

麻酔 65(2), 164-167, 2016-02
NAID 40020729210

統合失調症における前頭前野でのGAD67発現の低下 : Zif268発現変化の寄与 (特集 GABA作動性介在ニューロンの異常と統合失調症)

日本生物学的精神医学会誌 = Japanese journal of biological psychiatry 26(4), 192-198, 2015-12
NAID 40020734246

REPORT OF THE COMMITTEE : Diagnostic criteria for slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) (2012) : report by the Committee on Slowly Progressive Insulin-Dependent (Type 1) Diabetes Mellitus of the Japan Diabetes Society

Diabetology international 6(1), 1-7, 2015
NAID 40020406034

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★リンクテーブル★

リンク元	「glutamate decarboxylase」「グルタミン酸デカルボキシラーゼ」「GAD」
拡張検索	「anti-glutamic acid decarboxylase antibody」
関連記事	「glutamic」「decarboxylase」

「glutamate decarboxylase」

glutamic acid decarboxylase 2
Identifiers
Symbol	GAD2
Alt. symbols	GAD65
Entrez	2572
HUGO	11284
OMIM	4093
RefSeq	NM_001047
UniProt	Q05329
Other data
EC number	4.1.1.15
Locus	Chr. 10 p11.23

Glutamic acid decarboxylase 1
	GAD67 derivated from PDB 2okj
Identifiers
Symbol	GAD1
Alt. symbols	glutamate decarboxylase 1; (brain, 67kD); GAD67
Entrez	2571
HUGO	4092
OMIM	605363
RefSeq	NM_000817
UniProt	Q99259
Other data
EC number	4.1.1.15
Locus	Chr. 2 q31

glutamate decarboxylase
Identifiers
EC number	4.1.1.15
CAS number	9024-58-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI Protein	search