Human Succinic Semialdehyde Dehydrogenase
4-Aminobutyric acid (GABA) is an important inhibitor of synaptic transmission (Tillakaratne, Medina-Kauwe and Gibson, 1995) in the mammalian central nervous system (CNS). Although bound forms of GABA contribute to the free GABA pool in CNS, most GABA is derived from glutamic acid in a reaction catalyzed by glutamic acid decarboxylase. The carbon skeleton of GABA eventually enters the Krebs cycle through the sequential action of two enzymes. GABA-transaminase converts GABA to succinic semialdehyde, by the stoichiometric conversion of 2-oxoglutarate to glutamic acid, which replenishes the main GABA precursor. Succinic semialdehyde is then oxidized by NAD+-dependent succinic semialdehyde dehydrogenase (E.C. 126.96.36.199; SSADH) to form succinic acid, thus playing a key role in maintenance of GABA homeostasis. In addition, as an inborn error in the metabolism of a neurotransmitter (McKusick 271980), SSADH deficiency represents an unusual neurometabolic disease. SSADH deficiency has been reported in approximately 100 patients ranging from 3 months to 25 years of age at the time of diagnosis (Scriver and Gibson, 1995).
KeywordsAldehyde Dehydrogenase Transcription Initiation Site Polyadenylation Site Succinic Semialdehyde Human Chromosome 6p22
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