Aldehyde dehydrogenase 5 family, member A1 explained

Succinate-semialdehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH5A1 gene.^{[1] [2] [3]}

Function

This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD⁺-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter γ-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene.^[3]

Further reading

• Hearl WG, Churchich JE . Interactions between 4-aminobutyrate aminotransferase and succinic semialdehyde dehydrogenase, two mitochondrial enzymes . The Journal of Biological Chemistry . 259 . 18 . 11459–63 . Sep 1984 . 10.1016/S0021-9258(18)90883-5 . 6470007 . free .
• Chambliss KL, Hinson DD, Trettel F, Malaspina P, Novelletto A, Jakobs C, Gibson KM . Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) . American Journal of Human Genetics . 63 . 2 . 399–408 . Aug 1998 . 9683595 . 1377305 . 10.1086/301964 .
• Hogema BM, Akaboshi S, Taylor M, Salomons GS, Jakobs C, Schutgens RB, Wilcken B, Worthington S, Maropoulos G, Grompe M, Gibson KM . Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses . Molecular Genetics and Metabolism . 72 . 3 . 218–22 . Mar 2001 . 11243727 . 10.1006/mgme.2000.3145 .
• Aoshima T, Kajita M, Sekido Y, Ishiguro Y, Tsuge I, Kimura M, Yamaguchi S, Watanabe K, Shimokata K, Niwa T . Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T > A of the ALDH5A1 gene . Human Heredity . 53 . 1 . 42–4 . 2002 . 11901270 . 10.1159/000048603 . 25065695 .
• Blasi P, Boyl PP, Ledda M, Novelletto A, Gibson KM, Jakobs C, Hogema B, Akaboshi S, Loreni F, Malaspina P . Structure of human succinic semialdehyde dehydrogenase gene: identification of promoter region and alternatively processed isoforms . Molecular Genetics and Metabolism . 76 . 4 . 348–62 . Aug 2002 . 12208142 . 10.1016/S1096-7192(02)00105-1 .
• Novikov VD, Valova TA, Iasakova NT, Belan IB . [Morphological and functional characteristics of lymphocytes of mothers of children with Down syndrome] . Morfologii͡A . 118 . 4 . 74–80 . 2003 . 12629812 .
• Akaboshi S, Hogema BM, Novelletto A, Malaspina P, Salomons GS, Maropoulos GD, Jakobs C, Grompe M, Gibson KM . Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency . Human Mutation . 22 . 6 . 442–50 . Dec 2003 . 14635103 . 10.1002/humu.10288 . 2108/48106 . 20057400 . free .
• Plomin R, Turic DM, Hill L, Turic DE, Stephens M, Williams J, Owen MJ, O'Donovan MC . A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability . Molecular Psychiatry . 9 . 6 . 582–6 . Jun 2004 . 14981524 . 10.1038/sj.mp.4001441 . free .
• Kang JH, Park YB, Huh TL, Lee WH, Choi MS, Kwon OS . High-level expression and characterization of the recombinant enzyme, and tissue distribution of human succinic semialdehyde dehydrogenase . Protein Expression and Purification . 44 . 1 . 16–22 . Nov 2005 . 16199352 . 10.1016/j.pep.2005.03.019 .
• Blasi P, Palmerio F, Aiello A, Rocchi M, Malaspina P, Novelletto A . SSADH variation in primates: intra- and interspecific data on a gene with a potential role in human cognitive functions . Journal of Molecular Evolution . 63 . 1 . 54–68 . Jul 2006 . 16786440 . 10.1007/s00239-005-0154-8 . 2006JMolE..63...54B . 2108/32560 . 6067628 . free .
• Knerr I, Pearl PL, Bottiglieri T, Snead OC, Jakobs C, Gibson KM . Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (gamma-hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies in Aldh5a1-/- mice and characterization of gamma-hydroxybutyric acid pharmacology . Journal of Inherited Metabolic Disease . 30 . 3 . 279–94 . Jun 2007 . 17457693 . 10.1007/s10545-007-0574-2 . 20004337 .

Notes and References

1. Chambliss KL, Caudle DL, Hinson DD, Moomaw CR, Slaughter CA, Jakobs C, Gibson KM . Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde dehydrogenase from rat and human. cDNA isolation, evolutionary homology, and tissue expression . The Journal of Biological Chemistry . 270 . 1 . 461–7 . Jan 1995 . 7814412 . 10.1074/jbc.270.1.461 . free .
2. Book: Trettel F, Malaspina P, Jodice C, Novelletto A, Slaughter CA, Caudle DL, Hinson DD, Chambliss KL, Gibson KM . Human Succinic Semialdehyde Dehydrogenase . Enzymology and Molecular Biology of Carbonyl Metabolism 6 . Advances in Experimental Medicine and Biology . 414 . 253–60 . May 1997 . 9059628 . 10.1007/978-1-4615-5871-2_29 . 978-1-4613-7692-7 .
3. Web site: Entrez Gene: ALDH5A1 aldehyde dehydrogenase 5 family, member A1 (succinate-semialdehyde dehydrogenase).