ALAS1 explained
Delta-aminolevulinate synthase 1 also known as ALAS1 is a protein that in humans is encoded by the ALAS1 gene.[1] [2] ALAS1 is an aminolevulinic acid synthase.
Delta-aminolevulinate synthase catalyzes the condensation of glycine with succinyl-CoA to form delta-aminolevulinic acid. This nuclear-encoded mitochondrial enzyme is the first and rate-limiting enzyme in the mammalian heme biosynthetic pathway. There are 2 tissue-specific isozymes: a housekeeping enzyme encoded by the ALAS1 gene and an erythroid tissue-specific enzyme encoded by ALAS2.[2]
Mice lacking this gene exhibit embryonic lethality, indicating that ALAS is essential for early embryogenesis.[3]
Further reading
- Goodfellow BJ, Dias JS, Ferreira GC . The solution structure and heme binding of the presequence of murine 5-aminolevulinate synthase. . FEBS Lett. . 505 . 2 . 325–31 . 2001 . 11566198 . 10.1016/S0014-5793(01)02818-6 . 34879759 . etal. free .
- Cortesão E, Vidan J, Pereira J . Onset of X-linked sideroblastic anemia in the fourth decade. . Haematologica . 89 . 10 . 1261–3 . 2004 . 15477213 . etal.
- May BK, Bhasker CR, Bawden MJ, Cox TC . Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. . Mol. Biol. Med. . 7 . 5 . 405–21 . 1990 . 2095458 .
- Dwyer BE, Smith MA, Richardson SL . Down-Regulation of Aminolevulinate Synthase, the Rate-Limiting Enzyme for Heme Biosynthesis in Alzheimer's Disease . Neurosci. Lett. . 460 . 2 . 180–4 . 2009 . 19477221 . 10.1016/j.neulet.2009.05.058 . 2743886 . etal.
- Furuyama K, Sassa S . Multiple mechanisms for hereditary sideroblastic anemia . Cell. Mol. Biol. (Noisy-le-grand) . 48 . 1 . 5–10 . 2002 . 11929048 .
- Guberman AS, Scassa ME, Cánepa ET . Repression of 5-aminolevulinate synthase gene by the potent tumor promoter, TPA, involves multiple signal transduction pathways . Arch. Biochem. Biophys. . 436 . 2 . 285–96 . 2005 . 15797241 . 10.1016/j.abb.2005.02.011 . 11336/99172 . free .
- Roberts AG, Elder GH . Alternative splicing and tissue-specific transcription of human and rodent ubiquitous 5-aminolevulinate synthase (ALAS1) genes . Biochim. Biophys. Acta . 1518 . 1–2 . 95–105 . 2001 . 11267664 . 10.1016/s0167-4781(01)00187-7.
- Szafranski K, Schindler S, Taudien S . Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns . Genome Biol. . 8 . 8 . R154 . 2007 . 17672918 . 10.1186/gb-2007-8-8-r154 . 2374985 . etal . free .
- Scassa ME, Guberman AS, Ceruti JM, Cánepa ET . Hepatic nuclear factor 3 and nuclear factor 1 regulate 5-aminolevulinate synthase gene expression and are involved in insulin repression . J. Biol. Chem. . 279 . 27 . 28082–92 . 2004 . 15123725 . 10.1074/jbc.M401792200 . free . 20.500.12110/paper_00219258_v279_n27_p28082_Scassa . free .
- Imabayashi H, Mori T, Gojo S . Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis . Exp. Cell Res. . 288 . 1 . 35–50 . 2003 . 12878157 . 10.1016/S0014-4827(03)00130-7 . etal.
- Fujii H, Takahashi T, Matsumi M . Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure . Int. J. Mol. Med. . 14 . 6 . 1001–5 . 2004 . 15547665 . 10.3892/ijmm.14.6.1001. etal.
- Zheng J, Shan Y, Lambrecht RW . Differential regulation of human ALAS1 mRNA and protein levels by heme and cobalt protoporphyrin . Mol. Cell. Biochem. . 319 . 1–2 . 153–61 . 2008 . 18719978 . 10.1007/s11010-008-9888-0 . 33770538 . etal.
- Roberts AG, Redding SJ, Llewellyn DH . An alternatively-spliced exon in the 5'-UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem-mediated decay . FEBS Lett. . 579 . 5 . 1061–6 . 2005 . 15710391 . 10.1016/j.febslet.2004.12.080 . 32462861 . free .
- Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
- Jung M, Ohl F, Stephan C . [Quantifying gene expression in prostate carcinoma. Which endogenous reference genes are suitable?] . Urologe A . 46 . 9 . 1083–4 . 2007 . 17628775 . 10.1007/s00120-007-1436-0 . 11640176 . etal.
- Guberman AS, Scassa ME, Giono LE . Inhibitory effect of AP-1 complex on 5-aminolevulinate synthase gene expression through sequestration of cAMP-response element protein (CRE)-binding protein (CBP) coactivator . J. Biol. Chem. . 278 . 4 . 2317–26 . 2003 . 12433930 . 10.1074/jbc.M205057200 . etal. free . 20.500.12110/paper_00219258_v278_n4_p2317_Guberman . free .
- Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
- Ferreira GC, Cheltsov AV . Circular permutation of 5-aminolevulinate synthase as a tool to evaluate folding, structure and function . Cell. Mol. Biol. (Noisy-le-grand) . 48 . 1 . 11–6 . 2002 . 11929042 .
- Tsang HT, Connell JW, Brown SE . A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex . Genomics . 88 . 3 . 333–46 . 2006 . 16730941 . 10.1016/j.ygeno.2006.04.003 . etal.
Notes and References
- Bishop DF, Henderson AS, Astrin KH . Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome . Genomics . 7 . 2 . 207–14 . June 1990 . 2347585 . 10.1016/0888-7543(90)90542-3.
- Web site: Entrez Gene: Delta-aminolevulinate synthase 1 .
- Okano . S . Zhou . L . Kusaka . T . Shibata . K . Shimizu . K . Gao . X . Kikuchi . Y . Togashi . Y . Hosoya . T . Takahashi . S . Nakajima . O . Yamamoto . M . Indispensable function for embryogenesis, expression and regulation of the nonspecific form of the 5-aminolevulinate synthase gene in mouse. . Genes to Cells . January 2010 . 15 . 1 . 77–89 . 10.1111/j.1365-2443.2009.01366.x . 20015225. 25018156 . free .