Disease relevance of gamma-Oxybutyric acid

• It is presumed that, under pathological conditions (hepatic failure, alcoholic intoxication, succinic semialdehyde dehydrogenase defects), the rate of GHB synthesis or degradation in the peripheral organ is modified and induces increased GHB levels which could interfere with the normal brain mechanisms [1].
• Succinic semialdehyde couples stress response to quorum-sensing signal decay in Agrobacterium tumefaciens [2].
• Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to pharmacologic rescue, at 3-4 weeks of life [3].
• The principle of the procedure is based on the action of GABASE (GABA-aminotransferase plus succinic semialdehyde dehydrogenase), coupled to the detection of succinic semialdehyde and NADH, using Photobacterium luciferase [4].
• Two succinic semialdehyde dehydrogenases are induced when Escherichia coli K-12 Is grown on gamma-aminobutyrate [5].

Psychiatry related information on gamma-Oxybutyric acid

• Succinate-semialdehyde dehydrogenase (SSADH) deficiency is a rare cause of learning disability [6].
• Succinic semialdehyde dehydrogenase (SSADH) deficiency has predominantly neurological consequences, affecting psychomotor, speech and language development [7].

High impact information on gamma-Oxybutyric acid

• As a potential link between the half-cycles, we found that Rv1248c, annotated as encoding SucA, the putative E1 component of KDH, instead encodes alpha-ketoglutarate decarboxylase (Kgd) and produces succinic semialdehyde [8].
• GABA then is broken down, both within the cell and in the synaptic cleft by GABA transaminase to form succinic semialdehyde [9].
• These differences account for the substrate specificity for 4-carbon acid-aldehydes such as succinic semialdehyde and 2-carboxybenzaldehyde as well as for the idiosyncratic substrate aflatoxin B(1) dialdehyde of this subfamily of enzymes [10].
• Three rat brain cDNA clones approximately 3500, 1465, and 1135 base pairs in length encoding succinic semialdehyde dehydrogenase (SSADH; EC 1.2.1.24) were isolated from two cDNA libraries using a polymerase chain reaction derived probe [11].
• It is postulated that two enzymes, i.e. a NAD+-dependent dehydrogenase and a NADP+-dependent reductase, participate in the metabolism of succinic semialdehyde in the mitochondria matrix [12].

Chemical compound and disease context of gamma-Oxybutyric acid

• Cell extracts of Clostridium kluyveri, grown on ethanol plus succinate contained a succinyl-CoA:CoA transferase (0.28 U/mg), a coenzyme-A-dependent succinate-semialdehyde dehydrogenase (0.73 U/mg) and a NAD(+)-dependent 4-hydroxybutyrate dehydrogenase (0.25 U/mg) [13].
• Purification and characterization of a coenzyme-A-dependent succinate-semialdehyde dehydrogenase from Clostridium kluyveri [13].
• 4-Hydroxybutyric acid (4HB) is accumulated in succinic semialdehyde dehydrogenase deficiency, an inherited metabolic disease severely affecting the CNS during postnatal development [14].
• These include glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I), succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria), mevalonic aciduria, N-acetylaspartic aciduria (Canavan disease) and L-2-hydroxyglutaric aciduria [15].

Biological context of gamma-Oxybutyric acid

• Using this contig, we localized 124 sequence tagged sites, expressed sequence tags, and short tandem repeats including most of the markers in linkage with reading disability phenotypes, succinic semialdehyde dehydrogenase, GPLD1, prolactin, and 18 uncharacterized genes [16].
• Molecular analysis of two genes of the Escherichia coli gab cluster: nucleotide sequence of the glutamate:succinic semialdehyde transaminase gene (gabT) and characterization of the succinic semialdehyde dehydrogenase gene (gabD) [17].
• These sites are identical to the putative active site sequences of other brain succinic semialdehyde dehydrogenases [18].
• Structure of human succinic semialdehyde dehydrogenase gene: identification of promoter region and alternatively processed isoforms [19].
• Kinetics and mechanism of an NADPH-dependent succinic semialdehyde reductase from bovine brain [20].

Anatomical context of gamma-Oxybutyric acid

• Major goals were the demonstration of greater residual succinic semialdehyde dehydrogenase activity in patient cell lines and the better representation of physiology in vivo [21].
• In the gastrodin-treated group, both succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) immunoreactivities in the hippocampus was also decreased significantly, which stood in contrast to the nontreated group, in which strong SSADH and SSAR immunoreactivities were detected [22].
• The availability of [U-14C]succinic semialdehyde permits the reliable assay of succinic semialdehyde dehydrogenase in crude cell extracts of lymphocytes isolated from human blood, cultured human lymphoblasts, and other tissues where 4-aminobutyric acid metabolism is known to occur [23].
• Electron-cytochemical localization of succinic semialdehyde dehydrogenase activity in Purkinje neurons and hepatocytes of the rat [24].
• The method enabled the first determination of normal values for SSA in urine and pathological values of SSA in urine and cerebrospinal fluid samples derived from patients with succinic semialdehyde dehydrogenase deficiency [25].

Associations of gamma-Oxybutyric acid with other chemical compounds

• A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability [6].
• A second form of aldehyde reductase ("SSA reductase") specifically reduces succinic semialdehyde (SSA) to produce gamma-hydroxybutyrate [26].
• These isoenzymes are functionally distinct; with NADPH as cofactor, rAFAR1-1 has a low K(m) and high activity with CBA, whereas rAFAR2-2 exhibits a low K(m) and high activity towards succinic semialdehyde [27].
• The Q-Sepharose chromatography step resulted in the resolution of rAFAR2 into three peaks of AKR activity, two of which were purified and shown to be capable of catalysing the reduction of 2-carboxybenzaldehyde, succinic semialdehyde, 4-nitrobenzaldehyde and 9,10-phenathrenequinone [28].
• The increased formation of GABA in the presence of succinic semialdehyde was not due to an increased conversion of glutamate into GABA by glutamic acid decarboxylase [29].

Gene context of gamma-Oxybutyric acid

• In addition to reducing the dialdehydic form of aflatoxin B1-8,9-dihydrodiol, hAFAR shows high affinity for the gamma-aminobutyric acid metabolite succinic semialdehyde (SSA) which is structurally related to 2-CBA, suggesting that hAFAR could function as both a SSA reductase and a 2-CBA reductase in vivo [30].
• Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T > A of the ALDH5A1 gene [31].
• Two possible ALDH enzymes which might oxidize HNE in CNS mitochondria are ALDH2 and succinic semialdehyde dehydrogenase (SSADH/ALDH5A) [32].
• gamma-Aminobutyrate transaminase (GABA-T), a key enzyme of the GABA shunt, converts the major inhibitory neurotransmitter, GABA, to succinic semialdehyde [33].
• Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity [34].

Analytical, diagnostic and therapeutic context of gamma-Oxybutyric acid

• Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses [35].
• After treatment of the incubation mixture with phosphorylase a compound was isolated which is most likely the thiamine adduct of succinic semialdehyde [36].
• The succinic semialdehyde dehydrogenase (SSADH) null mouse (SSADH(-/-)) represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA) in brain, blood, and urine [37].
• Human succinic semialdehyde dehydrogenase. Molecular cloning and chromosomal localization [38].

References