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Gene Review

ALAS1  -  5'-aminolevulinate synthase 1

Homo sapiens

Synonyms: 5-aminolevulinate synthase, nonspecific, mitochondrial, 5-aminolevulinic acid synthase 1, ALAS, ALAS-H, ALAS3, ...
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Disease relevance of ALAS1


High impact information on ALAS1

  • This mutation resulted in decreased in vitro stability of bone marrow delta-aminolevulinate synthase activity [2].
  • V-erbA acts as a constitutive repressor of erythrocyte-specific gene transcription, arresting the expression of at least three different erythroid genes: the erythrocyte anion transporter (band 3), carbonic anhydrase II (CAII) and delta-aminolevulinate synthase (ALA-S) [4].
  • Upon exposure to drugs that induce cytochromes P450 and other drug-metabolizing enzymes, ALAS1 is transcriptionally up-regulated, increasing the rate of heme biosynthesis to provide heme for cytochrome P450 hemoproteins [5].
  • In nonerythropoietic cells, 5-aminolevulinate synthase (ALAS1) is the rate-limiting enzyme in heme biosynthesis [5].
  • Transcriptional activation of the ALAS1 gene is the first step in the coordinated up-regulation of apoprotein and heme synthesis in response to exogenous and endogenous signals controlling heme levels [5].

Biological context of ALAS1


Anatomical context of ALAS1

  • Using these different cDNAs, the human ALAS housekeeping gene (ALAS1) and the human erythroid-specific (ALAS2) gene have been localized to chromosomes 3p21 and X, respectively, by somatic cell hybrid and in situ hybridization techniques [6].
  • Differentiation of embryonic stem cells with a disrupted ALAS2 gene has established that expression of this gene is critical for erythropoiesis and cannot be compensated by expression of the ubiquitous isoform of the enzyme (ALAS1) [8].
  • While heme negatively regulates the synthesis of the housekeeping delta-aminolevulinate synthase (ALAS-N) in all non-erythroid cells, the expression of an erythroid-specific isozyme (ALAS-E) is developmentally regulated in red blood cells [9].
  • Two of the major organs producing heme are bone marrow and the liver. delta-Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis in hepatocytes as well as in erythroid cells [10].
  • The first enzyme, ALAS (5-aminolaevulinate synthase), occurs as an isoenzyme encoded on different chromosomes and is synthesized either as a housekeeping protein (ALAS-1) in all non-erythroid cell types, or only in differentiating erythroid precursor cells (ALAS-2) [11].

Associations of ALAS1 with chemical compounds

  • It has been shown that a deficiency of the erythroid-specific delta-aminolevulinate synthase (ALAS-E) activity is responsible for pyridoxine-responsive HSA in many patients, however, the pathogenesis of other types of HSA remains still unknown [12].
  • Induction of delta-aminolevulinate synthase and cytochrome P-450 hemoproteins in hepatocyte culture. Effect of glucose and hormones [13].
  • Increased glutathione in cultured hepatocytes associated with induction of cytochrome P-450. Lack of effect of glutathione depletion on induction of cytochrome P-450 and delta-aminolevulinate synthase [14].
  • In primary cultures of chick embryo hepatocytes pulse labeled with [35S]methionine, immunochemical analyses indicated that adenosine 3':5'-cyclic monophosphate (cAMP) did not affect either the rate of production or the maturation of delta-aminolevulinate synthase (ALA synthase) [15].
  • Glutathione depletion did not affect the ability of 2-propyl-2-isopropylacetamide to induce cytochrome P-450, glucuronidation of phenol red, or delta-aminolevulinate synthase [14].

Other interactions of ALAS1


Analytical, diagnostic and therapeutic context of ALAS1


  1. Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure. Fujii, H., Takahashi, T., Matsumi, M., Kaku, R., Shimizu, H., Yokoyama, M., Ohmori, E., Yagi, T., Sadamori, H., Tanaka, N., Akagi, R., Morita, K. Int. J. Mol. Med. (2004) [Pubmed]
  2. 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. Cotter, P.D., May, A., Fitzsimons, E.J., Houston, T., Woodcock, B.E., al-Sabah, A.I., Wong, L., Bishop, D.F. J. Clin. Invest. (1995) [Pubmed]
  3. Characterization of viable bacteria from Siberian permafrost by 16S rDNA sequencing. Shi, T., Reeves, R.H., Gilichinsky, D.A., Friedmann, E.I. Microb. Ecol. (1997) [Pubmed]
  4. Transcriptional repression of band 3 and CAII in v-erbA transformed erythroblasts accounts for an important part of the leukaemic phenotype. Fuerstenberg, S., Leitner, I., Schroeder, C., Schwarz, H., Vennström, B., Beug, H. EMBO J. (1992) [Pubmed]
  5. Identification of the xenosensors regulating human 5-aminolevulinate synthase. Podvinec, M., Handschin, C., Looser, R., Meyer, U.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome. Bishop, D.F., Henderson, A.S., Astrin, K.H. Genomics (1990) [Pubmed]
  7. An alternatively-spliced exon in the 5'-UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem-mediated decay. Roberts, A.G., Redding, S.J., Llewellyn, D.H. FEBS Lett. (2005) [Pubmed]
  8. Regulation of erythroid 5-aminolevulinate synthase expression during erythropoiesis. Sadlon, T.J., Dell'Oso, T., Surinya, K.H., May, B.K. Int. J. Biochem. Cell Biol. (1999) [Pubmed]
  9. Structure and regulation of the chicken erythroid delta-aminolevulinate synthase gene. Lim, K.C., Ishihara, H., Riddle, R.D., Yang, Z., Andrews, N., Yamamoto, M., Engel, J.D. Nucleic Acids Res. (1994) [Pubmed]
  10. Molecular mechanism of heme biosynthesis. Fujita, H. Tohoku J. Exp. Med. (1997) [Pubmed]
  11. Examination of mitochondrial protein targeting of haem synthetic enzymes: in vivo identification of three functional haem-responsive motifs in 5-aminolaevulinate synthase. Dailey, T.A., Woodruff, J.H., Dailey, H.A. Biochem. J. (2005) [Pubmed]
  12. Multiple mechanisms for hereditary sideroblastic anemia. Furuyama, K., Sassa, S. Cell. Mol. Biol. (Noisy-le-grand) (2002) [Pubmed]
  13. Induction of delta-aminolevulinate synthase and cytochrome P-450 hemoproteins in hepatocyte culture. Effect of glucose and hormones. Giger, U., Meyer, U.A. J. Biol. Chem. (1981) [Pubmed]
  14. Increased glutathione in cultured hepatocytes associated with induction of cytochrome P-450. Lack of effect of glutathione depletion on induction of cytochrome P-450 and delta-aminolevulinate synthase. Shedlofsky, S.I., Sinclair, P.R., Sinclair, J.F., Bonkovsky, H.L. Biochem. Pharmacol. (1984) [Pubmed]
  15. Biogenesis of liver delta-aminolevulinate synthase. The role of cAMP in the induction. Friedland, D.M., Ades, I.Z. FEBS Lett. (1985) [Pubmed]
  16. Assignment of the human housekeeping delta-aminolevulinate synthase gene (ALAS1) to chromosome band 3p21.1 by PCR analysis of somatic cell hybrids. Cotter, P.D., Drabkin, H.A., Varkony, T., Smith, D.I., Bishop, D.F. Cytogenet. Cell Genet. (1995) [Pubmed]
  17. Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization? Ohl, F., Jung, M., Xu, C., Stephan, C., Rabien, A., Burkhardt, M., Nitsche, A., Kristiansen, G., Loening, S.A., Radonić, A., Jung, K. J. Mol. Med. (2005) [Pubmed]
  18. Heme regulation of HeLa cell transferrin receptor number. Ward, J.H., Jordan, I., Kushner, J.P., Kaplan, J. J. Biol. Chem. (1984) [Pubmed]
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