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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The inhibitory neurotransmitter γ-aminobutyrate (GABA, 4-aminobutyrate) is generated in neurones by glutamic acid decarboxylase. GAD1 and GAD2 are differentially expressed during development, where GAD2 is thought to subserve a trophic role in early life and is distributed throughout the cytoplasm. GAD1 is expressed in later life and is more associated with nerve terminals  where GABA is principally accumulated in vesicles through the action of the vesicular inhibitory amino acid transporter SLC32A1. The role of γ-aminobutyraldehyde dehydrogenase (ALDH9A1) in neurotransmitter GABA synthesis is less clear. Following release from neurons, GABA may interact with either GABAA or GABAB receptors and may be accumulated in neurones and glia through the action of members of the SLC6 family of transporters. Successive metabolism through GABA transaminase and succinate semialdehyde dehydrogenase generates succinic acid, which may be further metabolized in the mitochondria in the tricarboxylic acid cycle.
* Key recommended reading is highlighted with an asterisk
Bien CG, Scheffer IE. (2011) Autoantibodies and epilepsy. Epilepsia, 52 Suppl 3: 18-22. [PMID:21542841]
* Errichiello L, Striano S, Zara F, Striano P. (2011) Temporal lobe epilepsy and anti glutamic acid decarboxylase autoimmunity. Neurol. Sci., 32 (4): 547-50. [PMID:21468678]
* Kim KJ, Pearl PL, Jensen K, Snead OC, Malaspina P, Jakobs C, Gibson KM. (2011) Succinic semialdehyde dehydrogenase: biochemical-molecular-clinical disease mechanisms, redox regulation, and functional significance. Antioxid. Redox Signal., 15 (3): 691-718. [PMID:20973619]
* McQuail JA, Frazier CJ, Bizon JL. (2015) Molecular aspects of age-related cognitive decline: the role of GABA signaling. Trends Mol Med, 21 (7): 450-60. [PMID:26070271]
* Pan ZZ. (2012) Transcriptional control of Gad2. Transcription, 3 (2): 68-72. [PMID:22414751]
* Verrotti A, Scaparrotta A, Olivieri C, Chiarelli F. (2012) Seizures and type 1 diabetes mellitus: current state of knowledge. Eur. J. Endocrinol., 167 (6): 749-58. [PMID:22956556]
1. Esclapez M, Tillakaratne NJ, Kaufman DL, Tobin AJ, Houser CR. (1994) Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms. J. Neurosci., 14 (3 Pt 2): 1834-55. [PMID:8126575]
2. Lippert B, Metcalf BW, Jung MJ, Casara P. (1977) 4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain. Eur. J. Biochem., 74 (3): 441-5. [PMID:856582]
3. Silverman RB. (2012) The 2011 E. B. Hershberg award for important discoveries in medicinally active substances: (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a GABA aminotransferase inactivator and new treatment for drug addiction and infantile spasms. J. Med. Chem., 55 (2): 567-75. [PMID:22168767]
4. Tao YH, Yuan Z, Tang XQ, Xu HB, Yang XL. (2006) Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives. Bioorg. Med. Chem. Lett., 16 (3): 592-5. [PMID:16290145]
5. Wu JY, Matsuda T, Roberts E. (1973) Purification and characterization of glutamate decarboxylase from mouse brain. J. Biol. Chem., 248 (9): 3029-34. [PMID:4700449]
Database page citation:
GABA turnover. Accessed on 24/03/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=764.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.