Gene Symbol: Alas2
Description: 5'-aminolevulinate synthase 2
Alias: 5-aminolevulinate synthase, erythroid-specific, mitochondrial, 5-aminolevulinic acid synthase 2, ALAS-E, Aminolevulinate synthase 2, delta, aminolevulinate, delta-, synthase 2, aminolevulinic acid synthase 2, erythroid, aminolevulinic acid synthase 2, erythroid-like, delta-ALA synthase 2, delta-ALA synthetase, delta-aminolevulinate synthase 2, erythroid-specific delta-aminolevulinate synthase ALAS-E
Species: rat
Products:     Alas2

Top Publications

  1. Cotter P, May A, Fitzsimons E, Houston T, Woodcock B, Al Sabah A, et al. Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. J Clin Invest. 1995;96:2090-6 pubmed
    ..sideroblastic anemia (XLSA) is caused by mutations of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) resulting in deficient heme synthesis...
  2. Cox T, Sadlon T, Schwarz Q, Matthews C, Wise P, Cox L, et al. The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis. Int J Biochem Cell Biol. 2004;36:281-95 pubmed
    ..pathway in erythroid cells is catalyzed by an erythroid-specific isoform of 5-aminolevulinate synthase-2 (ALAS2)...
  3. Ariyoshi T, Eguchi M, Muraki Y, Yasumatsu H, Suetsugu N, Arizono K. Effects of chlorinated benzenes of the activities of delta-aminolevulinic acid synthetase and heme oxygenase and on the content of hemoprotein in the liver of rats. J Pharmacobiodyn. 1981;4:69-76 pubmed
    ..The half-life of the fast phase was about 8 hr in control and about 6 or 13 hr in MCB- or TRCB-treated rats respectively. ..
  4. Kucerova J, Horvathova M, Mojzikova R, Belohlavkova P, Cermak J, Divoky V. New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine. Acta Haematol. 2011;125:193-7 pubmed publisher
    ..most common form is X-linked SA, which results from mutations in erythroid-specific ?-aminolevulinate synthase (ALAS2), the first enzyme in heme biosynthesis...
  5. Saxena G, Flora S. Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead poisoned rats. J Pharm Pharmacol. 2006;58:547-59 pubmed
    ..Certain other biochemical variables responded favourably to combination therapy and monotherapy with MiADMSA. Thus, supplementation of C. asiatica during chelation could be recommended for achieving optimum effects of chelation therapy. ..
  6. Barupala D, Dzul S, RIGGS GELASCO P, Stemmler T. Synthesis, delivery and regulation of eukaryotic heme and Fe-S cluster cofactors. Arch Biochem Biophys. 2016;592:60-75 pubmed publisher
  7. Abu Farha M, Niles J, Willmore W. Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition. Biochem Cell Biol. 2005;83:620-30 pubmed
    ..ALAS1 is ubiquitously expressed and provides heme for cytochromes and other hemoproteins. ALAS2 is expressed exclusively in erythroid cells and synthesizes heme specifically for haemoglobin...
  8. Harigae H, Suwabe N, Weinstock P, Nagai M, Fujita H, Yamamoto M, et al. Deficient heme and globin synthesis in embryonic stem cells lacking the erythroid-specific delta-aminolevulinate synthase gene. Blood. 1998;91:798-805 pubmed
    ..These results were confirmed using another ES differentiation system in vitro and suggest that ALAS-E expression, hence heme supply, is critical for the late stage of erythroid cell differentiation, which involves hemoglobin synthesis. ..
  9. Munakata H, Sun J, Yoshida K, Nakatani T, Honda E, Hayakawa S, et al. Role of the heme regulatory motif in the heme-mediated inhibition of mitochondrial import of 5-aminolevulinate synthase. J Biochem. 2004;136:233-8 pubmed
    ..By contrast, exogenous hemin did not affect the mitochondrial import of the erythroid-specific ALAS isoform (ALAS2) under the same experimental conditions...

More Information


  1. Lee P, Barton J, Rao S, Acton R, Adler B, Beutler E. Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in association with severe iron overload, and one with sideroblastic anemia and severe iron overload. Blood Cells Mol Dis. 2006;36:292-7 pubmed
    Mutations in aminolevulinate synthase 2 (ALAS2) are usually associated with sideroblastic anemia and iron overload...
  2. Dhar S, Takiguchi M, Arizono K, Ariyoshi T, Wakabayashi T. Nature of heme metabolizing enzymes in a mutant rat with hyperbilirubinuria. Res Commun Chem Pathol Pharmacol. 1993;80:329-36 pubmed
    ..The activity of heme oxygenase by CdCl2, a inducer of heme oxygenase, was considerably higher in EHBR than in control rats. These results indicate some specific hypersensitivity for heme metabolizing enzymes in EHBR. ..
  3. Haraguchi T, Yanaka N, Eguchi Y, Kudo T, Hirata A, Kato N. Fish oil feeding up-regulates the expression of 5-aminolevulinate synthase 2 mRNA in rat brain. Biosci Biotechnol Biochem. 2011;75:1383-5 pubmed
    ..the effect of fish oil on gene expression in the cerebral cortex, and found that 5-aminolevulinate synthase 2 (ALAS2) mRNA expression was up-regulated by fish oil feeding...
  4. Srivastava R, Dwivedi R, Kaur G, Srivastava R. Haem and drug-metabolizing enzymes in regenerating rat liver. Br J Exp Pathol. 1982;63:1-4 pubmed
  5. Ganter B, Tugendreich S, Pearson C, Ayanoglu E, Baumhueter S, Bostian K, et al. Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. J Biotechnol. 2005;119:219-44 pubmed
    ..We will demonstrate that gene expression events monitored in the liver can be used to predict pathological events occurring in that tissue as well as in hematopoietic tissues. ..
  6. Cotter P, Rucknagel D, Bishop D. X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley. Blood. 1994;84:3915-24 pubmed XLSA was identified as the deficient activity of the erythroid-specific form of delta-aminolevulinate synthase (ALAS2), the first enzyme in the heme biosynthetic pathway...
  7. Furuyama K, Sassa S. Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia. J Clin Invest. 2000;105:757-64 pubmed
  8. Cazzola M, May A, Bergamaschi G, Cerani P, Rosti V, Bishop D. Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females. Blood. 2000;96:4363-5 pubmed
    ..sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene. An elderly woman who presented with an acquired sideroblastic anemia is studied...
  9. To Figueras J, Ducamp S, Clayton J, Badenas C, Delaby C, Ged C, et al. ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria. Blood. 2011;118:1443-51 pubmed publisher
    ..X-linked dominant protoporphyria (XLDPP), which results from increased activity of 5-aminolevulinate synthase 2 (ALAS2), the rate-controlling enzyme of erythroid heme synthesis, led us to hypothesize that the CEP phenotype may be ..
  10. Uehara T, Kondo C, Yamate J, Torii M, Maruyama T. A toxicogenomic approach for identifying biomarkers for myelosuppressive anemia in rats. Toxicology. 2011;282:139-45 pubmed publisher
    ..Expression of the hemoglobin beta chain complex (Hbb), aminolevulinic acid synthase 2 (Alas2), and cell division cycle 25 homolog B (Cdc25b) genes changed as a result of anemia induced by the ..
  11. Senda N, Hoshi K, Fujino S. Effects of perphenazine, chlorpromazine or CoCl2 on the activities of delta-aminolevulinic acid synthetase and heme oxygenase and on the content of hemoprotein in rat liver. Res Commun Chem Pathol Pharmacol. 1989;65:57-64 pubmed
    ..In addition, CPZ resulted in a marked decrease of total heme content, but this content was not changed by PPZ. ..
  12. Ho Chen J, Bustamante J, Soares M. Prolactin-like protein-f subfamily of placental hormones/cytokines: responsiveness to maternal hypoxia. Endocrinology. 2007;148:559-65 pubmed
  13. Rokushima M, Omi K, Araki A, Kyokawa Y, Furukawa N, Itoh F, et al. A toxicogenomic approach revealed hepatic gene expression changes mechanistically linked to drug-induced hemolytic anemia. Toxicol Sci. 2007;95:474-84 pubmed
    ..They were Alas2, beta-glo, Eraf, Hmox1, Lgals3, and Rhced...
  14. Nakajima O, Takahashi S, Harigae H, Furuyama K, Hayashi N, Sassa S, et al. Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. EMBO J. 1999;18:6282-9 pubmed
    ..These results demonstrate that ALAS-E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells. ..
  15. Bustamante J, Dai G, Soares M. Pregnancy and lactation modulate maternal splenic growth and development of the erythroid lineage in the rat and mouse. Reprod Fertil Dev. 2008;20:303-10 pubmed
    ..In summary, the demands of pregnancy and lactation cause marked adaptations in the maternal spleen. The maternal spleen increases in size and exhibits an expansion of the erythroid lineage. ..
  16. Ajioka R, Phillips J, Kushner J. Biosynthesis of heme in mammals. Biochim Biophys Acta. 2006;1763:723-36 pubmed
    ..The biochemistry, structural biology and the mechanisms of tissue-specific regulation are presented in this review along with the key features of the porphyric disorders. ..
  17. Meguro K, Igarashi K, Yamamoto M, Fujita H, Sassa S. The role of the erythroid-specific delta-aminolevulinate synthase gene expression in erythroid heme synthesis. Blood. 1995;86:940-8 pubmed
    ..These findings thus indicate that heme formation, which is determined by the level of ALAS-E, plays an essential role on gene expression of many proteins necessary for erythroid development. ..
  18. Munakata H, Yamagami T, Nagai T, Yamamoto M, Hayashi N. Purification and structure of rat erythroid-specific delta-aminolevulinate synthase. J Biochem. 1993;114:103-11 pubmed
    ..Analysis of the papain-resistant core domain further revealed that it overlaps with the evolutionally conserved segment that has been noticed by sequence alignment analysis of ALA synthases from various species. ..
  19. Jaronczyk K, Bui L, Soong J, McLaughlin B, Marks G, Brien J, et al. The source of heme for vascular heme oxygenase II: de novo heme biosynthesis in rat aorta. Can J Physiol Pharmacol. 2004;82:218-24 pubmed