5 aminolevulinate synthetase

Summary

Summary: An enzyme of the transferase class that catalyzes condensation of the succinyl group from succinyl coenzyme A with glycine to form delta-aminolevulinate. It is a pyridoxyal phosphate protein and the reaction occurs in mitochondria as the first step of the heme biosynthetic pathway. The enzyme is a key regulatory enzyme in heme biosynthesis. In liver feedback is inhibited by heme. EC 2.3.1.37.

Top Publications

  1. ncbi Aberrant iron accumulation and oxidized status of erythroid-specific delta-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts
    Hideo Harigae
    Department of Molecular Diagnostics, Tohoku University School of Medicine, Sendai, Japan
    Blood 101:1188-93. 2003
  2. ncbi Cimetidine suppresses chemically induced experimental hepatic porphyria
    D L Marcus
    Department of Medicine, NYU Medical Center, New York 10016
    Am J Med Sci 300:214-7. 1990
  3. ncbi On the promoting action of tamoxifen in a model of hepatocarcinogenesis induced by p-dimethylaminoazobenzene in CF1 mice
    F Caballero
    Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP) (CONICET-FCEN, UBA, Ciudad Universitaria, , 2do piso, 1428, Buenos Aires, Argentina
    Int J Biochem Cell Biol 33:681-90. 2001
  4. ncbi Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on heme oxygenase-1, biliverdin IXalpha reductase and delta-aminolevulinic acid synthetase 1 in rats with wild-type or variant AH receptor
    Marjo Niittynen
    Department of Environmental Health, National Public Health Institute, Box 95, FI 70701 Kuopio, Finland
    Toxicology 250:132-42. 2008
  5. ncbi A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia
    Soumeya Bekri
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY, USA
    Blood 102:698-704. 2003
  6. pmc Involvement of delta-aminolaevulinate synthase encoded by the parasite gene in de novo haem synthesis by Plasmodium falciparum
    S Varadharajan
    Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, India
    Biochem J 367:321-7. 2002
  7. ncbi Effects of modulators of protein phosphorylation on heme metabolism in human hepatic cells: induction of delta-aminolevulinic synthase mRNA and protein by okadaic acid
    Edward E Cable
    Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA
    DNA Cell Biol 21:323-32. 2002
  8. ncbi Alterations of heme metabolism in lymphocytes and metal content in blood plasma as markers of diesel fuels effects on human organism
    V Muzyka
    Laboratory of Environmental Carcinogens, Institute of Experimental and Clinical Medicine, Tallinn, Estonia
    Sci Total Environ 286:73-81. 2002
  9. ncbi Regulatory network of tetrapyrrole biosynthesis--studies of intracellular signalling involved in metabolic and developmental control of plastids
    J Papenbrock
    , , Germany
    Planta 213:667-81. 2001
  10. ncbi Erythroid 5-aminolevulinate synthase, ferrochelatase and DMT1 expression in erythroid progenitors: differential pathways for erythropoietin and iron-dependent regulation
    Heinz Zoller
    Department of Medicine, University Hospital Innsbruck, Anichstrasse 25, A 6020 Innsbruck, Austria
    Br J Haematol 118:619-26. 2002

Research Grants

  1. GENETICS AND DEVELOPMENT OF ERYTHROID HEME ENZYMES
    Shigeru Sassa; Fiscal Year: 2002
  2. Gordon Research Conference on Tetrapyrroles
    Gloria Ferreira; Fiscal Year: 2002
  3. MECHANISM OF PORPHYRIA CAUSED BY TCDD
    Peter Sinclair; Fiscal Year: 2002
  4. Physiology of Malonyl-CoA in Muscle during Exercise
    WILLIAM WINDER; Fiscal Year: 2006
  5. Regulation of Skeletal Muscle LKB1
    WILLIAM WINDER; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications155 found, 100 shown here

  1. ncbi Aberrant iron accumulation and oxidized status of erythroid-specific delta-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts
    Hideo Harigae
    Department of Molecular Diagnostics, Tohoku University School of Medicine, Sendai, Japan
    Blood 101:1188-93. 2003
    ..These findings suggest that ALAS2 deficiency itself does not interfere with the development of definitive erythroid cells, but it results in a profound iron accumulation and a peroxidized state in erythroblasts...
  2. ncbi Cimetidine suppresses chemically induced experimental hepatic porphyria
    D L Marcus
    Department of Medicine, NYU Medical Center, New York 10016
    Am J Med Sci 300:214-7. 1990
    ..The effects of AIA and cimetidine on cytochrome P-450 were not additive, suggesting competition for a common site of interaction. The results suggest that cimetidine may prove to be useful in treating porphyria in humans...
  3. ncbi On the promoting action of tamoxifen in a model of hepatocarcinogenesis induced by p-dimethylaminoazobenzene in CF1 mice
    F Caballero
    Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP) (CONICET-FCEN, UBA, Ciudad Universitaria, , 2do piso, 1428, Buenos Aires, Argentina
    Int J Biochem Cell Biol 33:681-90. 2001
    ..This study reports that long-term treatment with TMX enhances hepatocarcinogenesis induced by DAB. The widespread use of TMX as an anticancer agent adds to the significance of this study...
  4. ncbi Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on heme oxygenase-1, biliverdin IXalpha reductase and delta-aminolevulinic acid synthetase 1 in rats with wild-type or variant AH receptor
    Marjo Niittynen
    Department of Environmental Health, National Public Health Institute, Box 95, FI 70701 Kuopio, Finland
    Toxicology 250:132-42. 2008
    ..Other factors such as the late repression of BVRA found here and possibly oxidative stress may be important contributors to biliverdin accumulation in these rats...
  5. ncbi A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia
    Soumeya Bekri
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY, USA
    Blood 102:698-704. 2003
    ..The dramatic decreases in reporter activity and mRNA level suggest that the region of the mutation may bind a novel and important erythroid regulatory element...
  6. pmc Involvement of delta-aminolaevulinate synthase encoded by the parasite gene in de novo haem synthesis by Plasmodium falciparum
    S Varadharajan
    Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, India
    Biochem J 367:321-7. 2002
    ..The Pf ALAS gene is functional and vital for parasite haem synthesis and parasite survival...
  7. ncbi Effects of modulators of protein phosphorylation on heme metabolism in human hepatic cells: induction of delta-aminolevulinic synthase mRNA and protein by okadaic acid
    Edward E Cable
    Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA
    DNA Cell Biol 21:323-32. 2002
    ..Wortmannin diminished the heme-mediated induction of heme oxygenase-1 mRNA in HepG2 cells, but not Huh-7 cells. These results report a novel property of okadaic acid to affect heme metabolism in human cell lines...
  8. ncbi Alterations of heme metabolism in lymphocytes and metal content in blood plasma as markers of diesel fuels effects on human organism
    V Muzyka
    Laboratory of Environmental Carcinogens, Institute of Experimental and Clinical Medicine, Tallinn, Estonia
    Sci Total Environ 286:73-81. 2002
    ..05). The disturbances of heme metabolism in lymphocytes and zinc level in blood plasma caused by diesel fuel exposure seems to be a useful biomarkers for carcinogenic risk assessment...
  9. ncbi Regulatory network of tetrapyrrole biosynthesis--studies of intracellular signalling involved in metabolic and developmental control of plastids
    J Papenbrock
    , , Germany
    Planta 213:667-81. 2001
    ..Recent reports about plastid-localised control mechanisms for plant tetrapyrrole metabolism are summarised and compared with results obtained in experiments on nucleus-plastid communication...
  10. ncbi Erythroid 5-aminolevulinate synthase, ferrochelatase and DMT1 expression in erythroid progenitors: differential pathways for erythropoietin and iron-dependent regulation
    Heinz Zoller
    Department of Medicine, University Hospital Innsbruck, Anichstrasse 25, A 6020 Innsbruck, Austria
    Br J Haematol 118:619-26. 2002
    ..These data provide new insights into the complex biochemical interaction between iron metabolism, haem biosynthesis and EPO biology...
  11. pmc Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia
    K Furuyama
    Laboratory of Biochemical Hematology, The Rockefeller University, New York, New York 10021, USA
    J Clin Invest 105:757-64. 2000
    ....
  12. pmc Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload
    O Nakajima
    Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305 8577, USA
    EMBO J 18:6282-9. 1999
    ..These results demonstrate that ALAS-E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells...
  13. ncbi Tissue-specific expression of ALA synthase-1 and heme oxygenase-1 and their expression in livers of rats chronically exposed to ethanol
    Jianyu Zheng
    Liver Biliary Pancreatic Center, Carolinas Medical Center, 1000 Blythe Boulevard, Charlotte, NC 28203, USA
    FEBS Lett 582:1829-34. 2008
    ..These results provide novel insights into the effects of chronic ethanol consumption on hepatic heme biosynthesis and porphyrias...
  14. ncbi Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia
    Y Shimada
    Otsuka GEN Research Institute, Otsuka Pharmaceutical Company Ltd, Tokushima, Japan
    J Hum Genet 43:115-22. 1998
    ..1-q13.3 by fluorescence in-situ hybridization. As band Xq13 has been implicated in X-linked sideroblastic anemia with spinocerebellar ataxia, hABC7 becomes a candidate gene for this heritable disorder...
  15. ncbi Novel regulation of delta-aminolevulinate synthase in the rat harderian gland
    M Nagai
    Rockefeller University, New York, NY 10021, USA
    Biochem Pharmacol 53:643-50. 1997
    ..The constitutive expression of the ALAS-N gene in the Harderian gland suggests a novel transcriptional control mechanism of this gene...
  16. ncbi Decrease of hepatic delta-aminolevulinate dehydratase activity in an animal model of fatigue
    Tsuyoshi Tahara
    Department of Physiology, Osaka City University Graduate School of Medicine, 1 4 3 Asahimachi, Abeno Ku, Osaka 545 8585, Japan
    Biochem Biophys Res Commun 353:1068-73. 2007
    ..Although this level of increase in the plasma concentration of ALA may not induce fatigue, increase in plasma and urinary ALA levels can be biomarkers of fatigue...
  17. ncbi 5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi
    Maria Elisa Lombardo
    Centro de Investigaciones sobre Porfirinas y Porfirias CIPYP CONICET FCEN, UBA, Ciudad Universitaria Pabellón II 2do, Piso, 1428 Buenos Aires, Argentina
    Int J Biochem Cell Biol 35:1263-71. 2003
    ..The aim of this study has been to investigate the presence of metabolites and enzymes of porphyrin pathway, as well as ALA formation in epimastigotes of T. cruzi, Tulahuén strain, Tul 2 stock...
  18. ncbi PGC-1alpha: looking behind the sweet treat for porphyria
    Dangsheng Li
    Cell Press, Cambridge, Massachusetts 02138, USA
    Cell 122:487-9. 2005
    ..In this issue of Cell, reveal that a transcriptional coactivator called PGC-1alpha is a key player in both induction of porphyria by fasting and amelioration of the symptoms by glucose treatment...
  19. pmc Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans
    Isabel Astner
    Division of Structural Biology, German Research Centre for Biotechnology, Braunschweig, Germany
    EMBO J 24:3166-77. 2005
    ..Mutations are found to obstruct substrate binding, disrupt the dimer interface, or hamper the correct folding. The structure of ALAS completes the structural analysis of enzymes in heme biosynthesis...
  20. pmc Iron-dependent cytochrome c1 expression is mediated by the status of heme in Bradyrhizobium japonicum
    Tao Gao
    Department of Biochemistry, 140 Farber Hall, State University of New York at Buffalo, Buffalo, NY 14214, USA
    J Bacteriol 187:5084-9. 2005
    ..We suggest that iron-dependent cytochrome c1 expression is mediated by heme availability for heme protein formation...
  21. ncbi Repression of 5-aminolevulinate synthase gene by the potent tumor promoter, TPA, involves multiple signal transduction pathways
    Alejandra S Guberman
    Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon II Piso 4, Ciudad Universitaria, 1428 Buenos Aires, Argentina
    Arch Biochem Biophys 436:285-96. 2005
    ..Finally, by overexpression of a constitutively active p90RSK and the coactivator, cAMP-response element protein (CREB)-binding protein (CBP), we reinforced our previous model, that implies competition between AP-1 and CREB for CBP...
  22. ncbi An alternatively-spliced exon in the 5'-UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem-mediated decay
    Andrew G Roberts
    Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK
    FEBS Lett 579:1061-6. 2005
    ..These data suggest that translation of ALAS1 mRNA itself might be required for destabilisation in response to haem...
  23. pmc Examination of mitochondrial protein targeting of haem synthetic enzymes: in vivo identification of three functional haem-responsive motifs in 5-aminolaevulinate synthase
    Tamara A Dailey
    Department of Microbiology, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602 7229, USA
    Biochem J 386:381-6. 2005
    ..Ferrochelatase, the terminal enzyme, possesses a typical N-terminal leader sequence and no evidence of a role for the C-terminus was found in mitochondrial targeting...
  24. ncbi The source of heme for vascular heme oxygenase II: de novo heme biosynthesis in rat aorta
    Kinga Jaronczyk
    Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen s University, Kingston, ON, Canada
    Can J Physiol Pharmacol 82:218-24. 2004
    ....
  25. ncbi Free heme pool and activity of key enzyme of heme synthesis in the rat liver under action of agents affecting reduced glutathione level
    T V Barannik
    Karazin, Kharkiv National University, Ukraine
    Ukr Biokhim Zh 77:120-2. 2005
    ..The further experiments should be performed in order to elucidate the mechanisms of GSH level influence on free heme pool formation in the liver cells...
  26. ncbi The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis
    Timothy C Cox
    School of Molecular and Biomedical Science, University of Adelaide, SA 5005, Adelaide, Australia
    Int J Biochem Cell Biol 36:281-95. 2004
    ..We conclude that the major splice isoform of ALAS2 is functional in vivo and could significantly contribute to erythroid heme biosynthesis and hemoglobin formation...
  27. ncbi Volatile anaesthetics induce biochemical alterations in the heme pathway in a B-lymphocyte cell line established from hepatoerythropoietic porphyria patients (LBHEP) and in mice inoculated with LBHEP cells
    Ana Maria Buzaleh
    Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Centro de Investigaciones sobre Porfirinas y Porfirias CIPYP, University of Buenos Aires, CONICET, Buenos Aires, Argentina
    Int J Biochem Cell Biol 36:216-22. 2004
    ....
  28. ncbi [Activity of key enzymes of heme metabolism and cytochrome P-450 content in the rat liver in experimental rhabdomyolysis and hemolytic anemia]
    P A Kaliman
    Karazin Kharkov National University, Ukraine
    Ukr Biokhim Zh 75:109-14. 2003
    ..The effect of heme arrival from the blood stream, as well as a direct influence of glycerol and phenylhydrazine on the investigated parameters are discussed...
  29. ncbi Protective role of heme oxygenase-1 induction in carbon tetrachloride-induced hepatotoxicity
    Kiichi Nakahira
    Department of Anesthesiology and Resuscitology, Okayama University Medical School, 2 5 1 Shikata cho, Okayama 700 8558, Japan
    Biochem Pharmacol 66:1091-105. 2003
    ..Our findings also suggest that HO-1 induction may play an important role in conferring protection on hepatocytes from oxidative damage caused by free heme...
  30. pmc High-level production of porphyrins in metabolically engineered Escherichia coli: systematic extension of a pathway assembled from overexpressed genes involved in heme biosynthesis
    Seok Joon Kwon
    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Saint Paul, Minnesota 55108, USA
    Appl Environ Microbiol 69:4875-83. 2003
    ..These results may indicate that heme has a regulatory impact on the iron uptake of E. coli or that the ferrochelatase is inactive in vivo due to an incompatible enzyme interaction...
  31. ncbi Bilirubin is highly effective in preventing in vivo delta-aminolevulinic acid-induced oxidative cell damage
    Guillermo O Noriega
    Centro de Investigaciones sobre Porfirinas y Porfirias CIPYP, CONICET Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
    Biochim Biophys Acta 1638:173-8. 2003
    ..These results add further support to the proposal assigning bilirubin a key protective role against oxidative damage here induced by ALA...
  32. ncbi The role of the erythroid-specific delta-aminolevulinate synthase gene expression in erythroid heme synthesis
    K Meguro
    Rockefeller University, New York, NY 10021, USA
    Blood 86:940-8. 1995
    ..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...
  33. pmc Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts
    H L Bonkowsky
    J Clin Invest 56:1139-48. 1975
    ..This deficiency is probably responsible for protoporphyrin accumulation and hence the biochemical and clinical features observed in protoporphyria...
  34. ncbi Structure, turnover, and heme-mediated suppression of the level of mRNA encoding rat liver delta-aminolevulinate synthase
    M Yamamoto
    Department of Biochemistry, Toyama Medical and Pharmaceutical University School of Medicine, Japan
    J Biol Chem 263:15973-9. 1988
    ..The results provide convincing evidence that heme inhibits the transcription of delta-aminolevulinate synthase mRNA...
  35. pmc Characterization of a Bradyrhizobium japonicum ferrochelatase mutant and isolation of the hemH gene
    J M Frustaci
    Department of Biochemistry, State University of New York, Buffalo 14214
    J Bacteriol 174:4223-9. 1992
    ..The data show that B. japonicum ferrochelatase is essential for normal nodule development...
  36. ncbi Hepatic heme and drug metabolism in rats with chronic mountain sickness
    H L Bonkovsky
    Am J Physiol 251:G467-74. 1986
    ..Thus the oxygen-requiring processes of hepatic heme and drug metabolism were well maintained despite chronic profound hypoxia sufficient to cause cardiopulmonary complications...
  37. ncbi Hypoxic up-regulation of erythroid 5-aminolevulinate synthase
    Thomas Hofer
    Institute of Veterinary Physiology, University of Zurich, Switzerland
    Blood 101:348-50. 2003
    ..Mutation of a previously predicted HIF-1-binding site (-323/-318) within this promoter fragment and DNA-binding assays revealed that hypoxic up-regulation is independent of this putative HIF-1 DNA-binding site...
  38. ncbi Heme biosynthesis pathway regulation in a model of hepatocarcinogenesis pre-initiation
    C F Polo
    Centro de Investigaciones sobre Porfirinas y Porfirias CIPYP, CONICET y FCEN, UBA, Ciudad Universitaria, Republic of Argentina
    Comp Biochem Physiol B 103:251-6. 1992
    ....
  39. ncbi Biosynthesis of delta-aminolevulinic acid and the regulation of heme formation by immature erythroid cells in man
    L C Gardner
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, United Kingdom
    J Biol Chem 266:22010-8. 1991
    ....
  40. ncbi Activities of haem synthetic enzymes in blood cells of pre-natal flexed-tailed (f/f) anaemic mice
    R J Cole
    J Embryol Exp Morphol 34:373-86. 1975
    ....
  41. ncbi Up-regulation of CYP2A5 expression by porphyrinogenic agents in mouse liver
    P Salonpää
    Department of Pharmacology and Toxicology, University of Oulu, Finland
    Naunyn Schmiedebergs Arch Pharmacol 351:446-52. 1995
    ..These results show that porphyrinogenic agents act as efficient inducers of CYP2A5, and suggest that regulation of the transcription of the Cyp2a-5 gene could in some instances involve heme-sensitive factors...
  42. ncbi Fast track to the porphyrias
    John D Phillips
    Nat Med 11:1049-50. 2005
  43. ncbi Relative potencies of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls derived from hepatic porphyrin accumulation in mice
    A P van Birgelen
    U S Environmental Protection Agency, National Health and EnvironmentalResearch Laboratory, Research Triangle Park, North Carolina 27711, USA
    Toxicol Appl Pharmacol 138:98-109. 1996
    ..However, the higher potencies of the mono-ortho-substituted PCBs have important implications for risk assessment of these compounds...
  44. ncbi Role of AMP-activated protein kinase in the molecular adaptation to endurance exercise
    William W Winder
    Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA
    Med Sci Sports Exerc 38:1945-9. 2006
    ..These observations lend credence to the hypothesis that AMPK activation induced by muscle contraction is responsible in part for adaptations to endurance exercise training...
  45. ncbi Expression of genes involved in heme biosynthesis in the human retinoblastoma cell lines WERI-Rb-1 and Y79: implications for photodynamic therapy
    E Ruiz-Galindo
    Lab de Citopatología Ambiental, Escuela Nacional de Ciencias Biologicas del Instituto Politecnico Nacional, Universidad Nacional Autonoma de Mexico, Mexico, DF, Mexico
    J Exp Clin Cancer Res 26:195-200. 2007
    ..PpIX levels were 15- and 18-fold higher in WERI-Rb-1 and Y79 cells, respectively, following induction by delta-aminolevulinic acid. PDT may thus be a promising treatment in vitro, at least in these two retinoblastoma cell lines...
  46. ncbi Regulation of human liver delta-aminolevulinic acid synthase by bile acids
    Anne Kathrin Peyer
    Division of Pharmacology and Neurobiology, Biozentrum, University of Basel, Basel, Switzerland
    Hepatology 46:1960-70. 2007
    ..These data also suggest that elevated endogenous bile acids may precipitate neuropsychiatric attacks in patients with acute hepatic porphyrias...
  47. ncbi Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation
    Ida Annunziata
    Institute of Genetics and Biophysics Adriano Buzzati Traverso, CNR, Naples, Italy
    Am J Med Genet A 118:217-22. 2003
    ..So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene...
  48. ncbi The effect of lead bioaccumulation on haem biosynthetic enzymes in fish
    S A Haffor
    Zoology Department, Faculty of Science, King Saud University, Riyadh, Saudi Arabia
    J Environ Biol 24:271-80. 2003
    ..The activity of the haem catabolic enzyme, haem oxygenase, was increased by concentration and length of time to lead exposure...
  49. ncbi D-glucose enhanced 5-aminolevulinic acid production in recombinant Escherichia coli culture
    Xiao Xia Liu
    School of Biology and Chemical Engineering, Jiaxing University, Jiaxing 314001, China
    Appl Biochem Biotechnol 160:822-30. 2010
    ..In jar fermenter, final extracellular ALA concentration reached 3.1 g/L by feeding with D-glucose...
  50. ncbi Structure of the Bradyrhizobium japonicum gene hemA encoding 5-aminolevulinic acid synthase
    C R McClung
    Gene 54:133-9. 1987
    ..There is also one block of 9 nt found in both the B. japonicum glnA and hemA promoter regions...
  51. ncbi Effect of altered iron metabolism on markers of haem biosynthesis and intestinal iron absorption in mice
    A H Laftah
    Department of Life Sciences, King s College, Franklin Wilkins Building, Stamford Street, London, SE1 9NN, UK
    Ann Hematol 84:177-82. 2005
    ..This study further supports the hypothesis that alterations in haem biosynthesis influence duodenal iron absorption. ALA in particular appears to function as a modulator in controlling intestinal iron absorption...
  52. ncbi 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
    Pauline L Lee
    The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, MEM 215, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 36:292-7. 2006
    ..Thus, ALAS2 mutations might contribute to more severe iron loading in persons with primary hemochromatosis...
  53. ncbi Effect of Tin-mesoporphyrin, an inhibitor of haem catabolism, on intestinal iron absorption
    Abas H Laftah
    Department of Clinical Biochemistry, GKT School of Medicine and Dentistry Department of Life Sciences, King s College London, London, UK
    Br J Haematol 122:298-304. 2003
    ..05) in both mucosal iron uptake and Fe(III) reducing activity. We conclude that intermediates in haem metabolism, in particular levels of ALA, may play a role in duodenal iron absorption...
  54. ncbi Sex comparison of heme pathway in rats bearing hepatic tumors
    R Wainstok de Calmanovici
    , Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
    Tumori 77:379-84. 1991
    ..e) The heme pathway was functional in DENA induced tumors in both male and female rats but they were little affected by HCB...
  55. ncbi [Gene defects identified in porphyrias and their participation in onset of this disease]
    Reiko Akagi
    Nihon Yakurigaku Zasshi 130:266-9. 2007
  56. ncbi Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis
    B K May
    Department of Biochemistry, University of Adelaide, Australia
    Mol Biol Med 7:405-21. 1990
    ..The human erythroid ALAS gene is located on the X-chromosome, suggesting that a defect in this gene may be responsible for X-linked sideroblastic anemias...
  57. ncbi Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia
    Mario Cazzola
    Department of Hematology, University of Pavia Medical School and Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Policlinico S Matteo, Pavia, Italy
    Blood 101:1996-2000. 2003
    ..These findings suggest that most of the iron deposited in perinuclear mitochondria of ring sideroblasts is present in the form of MtF and that this latter might be a specific marker of sideroblastic anemia...
  58. ncbi Molecular epidemiology of erythropoietic protoporphyria in the U.K
    S D Whatley
    Department of Medical Biochemistry and Immunology, University Hospital of Wales and School of Medicine, Cardiff University, Cardiff CF14 4XN, U K
    Br J Dermatol 162:642-6. 2010
    ..Predictive genetic counselling requires accurate molecular diagnosis and knowledge of patterns of inheritance...
  59. ncbi Coumarin-induced changes in delta-aminolaevulinic acid synthase and cytochrome P-450 in chick embryo liver
    D E Goeger
    Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550
    Food Chem Toxicol 29:145-51. 1991
    ..Because the chick embryo liver hydroxylates coumarin at position 7 in a manner similar to humans, it may be a more suitable model than the rat for studying some of the metabolic effects of coumarin...
  60. ncbi Misregulation of tetrapyrrole biosynthesis in transgenic tobacco seedlings expressing mammalian biliverdin reductase
    Keara A Franklin
    School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
    Plant J 35:717-28. 2003
    ....
  61. ncbi Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
    A M Buzaleh
    Centro de Investigaciones sobre Porfirinas y Porfirias CIPYP CONICET, Buenos Aires, Argentina
    Cell Mol Biol (Noisy-le-grand) 55:38-44. 2009
    ..These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias...
  62. pmc Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis
    Achille Iolascon
    Department of Biochemistry and Medical Biotechnologies, University Federico II, Naples, Italy
    Haematologica 94:395-408. 2009
    ..This information could be useful in the diagnosis and classification of these microcytic anemias...
  63. ncbi The site of inhibition of porphyrin biosynthesis by an isomer of diazinon in rats
    A W Nichol
    Biochem Pharmacol 32:2653-7. 1983
    ....
  64. ncbi Purification and structure of rat erythroid-specific delta-aminolevulinate synthase
    H Munakata
    Department of Biochemistry, Tohoku University School of Medicine, Sendai
    J Biochem 114:103-11. 1993
    ..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...
  65. ncbi Isolation and nucleotide sequence of the 5-aminolevulinate synthase gene from Aspergillus nidulans
    R E Bradshaw
    Leicester Biocentre, University of Leicester, UK
    Curr Genet 23:501-7. 1993
    ..Under the conditions used the transcription of hemA was unaffected by dextrose repression, heat shock, or oxygen levels...
  66. ncbi Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis
    Rebecca A Wingert
    Stem Cell Program and Division Hematology Oncology Children s Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 436:1035-39. 2005
    ..These findings uncover a connection between haem biosynthesis and Fe-S clusters, indicating that haemoglobin production in the differentiating red cell is regulated through Fe-S cluster assembly...
  67. ncbi X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase
    T C Cox
    Department of Biochemistry, University of Adelaide, Australia
    N Engl J Med 330:675-9. 1994
    ..The recently identified gene for an erythroid-specific 5-aminolevulinate synthase isoenzyme and its localization to the X chromosome make it likely that one or more defects in this gene underlie the anemia...
  68. ncbi Testing the porphyrinogenicity of propofol in a primed rat model
    H Bohrer
    Department of Anaesthesia, University of Heidelberg, Germany
    Br J Anaesth 75:334-8. 1995
    ..71 and 3.54 nmol g-1 in the AIA-primed groups. Hepatic ALAS activity was 29.2 and 35.5 nmol h-1 g-1 in groups 1 and 2. In the primed saline group, ALAS activity was measured at 134.5 nmol h-1 g-1.(ABSTRACT TRUNCATED AT 250 WORDS)..
  69. ncbi Regulation and gene expression of heme synthesis under heavy metal exposure--review
    Avital Schauder
    The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel
    J Environ Pathol Toxicol Oncol 29:137-58. 2010
    ..Main risk factors are described as well as effects on iron dependent processes in order to increase public awareness to the distribution of heavy metals in our close environment and the harsh consequences of exposure, even in low doses...
  70. ncbi Transformation, growth rate, and the heme biosynthetic pathway in V-abl-transfected fibroblasts
    R Mamet
    Laboratory of Biochemical Pharmacology, Beilinson Medical Center, Petah Tiqua, Israel
    Biochem Med Metab Biol 52:53-7. 1994
    ..The relationships between transformation, growth rate, and heme biosynthetic pathway are discussed...
  71. ncbi The effects of bromocriptine and prolactin on porphyrin biosynthesis in the harderian gland of the male hamster, Mesocritecus auratus
    F A Marr
    Department of Anatomy, University of Glasgow, UK
    J Comp Physiol B 164:524-9. 1995
    ..The results support the hypothesis that, while androgens have an inhibitory effect on porphyrin synthesis within this model, other factors, including prolactin, are permissive...
  72. ncbi Complete nucleotide sequence of hepatic 5-aminolaevulinate synthase precursor
    I A Borthwick
    Eur J Biochem 150:481-4. 1985
    ..The latter presequence is highly basic in character as found with other mitochondrial preproteins...
  73. pmc Role of the hemA gene product and delta-aminolevulinic acid in regulation of Escherichia coli heme synthesis
    E Verderber
    Somatogen, Inc, Boulder, Colorado 80301 2857, USA
    J Bacteriol 179:4583-90. 1997
    ..A. Hart, P. T. Kallio, and J. E. Bailey, Appl. Environ. Microbiol. 60:2431-2437, 1994), who concluded that ALA formation is not the rate-limiting step in E. coli cells expressing Vitreoscilla hemoglobin...
  74. ncbi Altered heme pathway regulation and drug metabolizing enzyme system in a mouse model of hepatocarcinogenesis: effect of veronal
    E Gerez
    Centro de Investigaciones sobre Porfirinas y Porfirias CIPYP, CONICET FCEN, UBA, Ciudad Universitaria, Buenos Aires, Argentina
    Gen Pharmacol 29:569-73. 1997
    ..3. The alterations found here would give rise to a pattern distinctive to that usually observed in the so-called resistant hepatocyte...
  75. ncbi Arg452 substitution of the erythroid-specific 5-aminolaevulinate synthase, a hot spot mutation in X-linked sideroblastic anaemia, does not itself affect enzyme activity
    Kazumichi Furuyama
    Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi ken, Japan
    Eur J Haematol 76:33-41. 2006
    ....
  76. ncbi Intracellular redistribution of heme in rat liver under oxidative stress: the role of heme synthesis
    Pavel A Kaliman
    Biochemistry Department, Kharkiv National University, 61077 Kharkiv, Ukraine
    Cell Biol Int 29:9-14. 2005
    ..Thus heme synthesis can greatly contribute to heme intracellular redistribution under oxidative stress...
  77. ncbi Respiratory uncoupling induces delta-aminolevulinate synthase expression through a nuclear respiratory factor-1-dependent mechanism in HeLa cells
    B Li
    Departments of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 274:17534-40. 1999
    ..These data suggest that the transcription factor NRF-1 plays a key role in cellular adaptation to energy demands by translating physiological signals into an increased capacity for generating energy...
  78. ncbi Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene
    M F Kramer
    Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, FL 33612 4799, USA
    Gene 247:153-66. 2000
    ..This is the first study to delimit the cis-acting region responsible for activation of the ALAS2 promoter upon dimethyl-sulfoxide induction in MEL cells...
  79. pmc Effects of expression of hemA and hemB genes on production of porphyrin in Propionibacterium freudenreichii
    Yongzhe Piao
    Department of Biotechnology, Graduate School of Engineering, Osaka University, Yamada oka 2 1, Suita, Osaka 565 0871, Japan
    Appl Environ Microbiol 70:7561-6. 2004
    ....
  80. ncbi Low oxygen concentration as a general physiologic regulator of erythropoiesis beyond the EPO-related downstream tuning and a tool for the optimization of red blood cell production ex vivo
    Marija Vlaski
    Aquitaine Limousin Branch of French Blood Institute, Bordeaux, France
    Exp Hematol 37:573-84. 2009
    ..However, hypoxia seems to influence erythropoiesis beyond this well-known mechanism. The aim of our study is to test this hypothesis adapting the oxygenation level to each stage of erythropoiesis...
  81. ncbi [Construction of recombinant vector expressing ALAS2 gene in X-linked sideroblastic anemia]
    Yi Qun Wang
    Department of Hematology, The First Hospital, Peking University, Beijing 100034, China
    Zhongguo Shi Yan Xue Ye Xue Za Zhi 12:687-93. 2004
    ..So, the vector has the potential in gene replacement and can be used for patients with XLSA in future...
  82. ncbi Rhodanese and ALA-S in mammary tumor and liver from normal and tumor-bearing mice
    N M Navone
    Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET, FCEN, UBA, Buenos Aires, Argentina
    Comp Biochem Physiol B 102:83-5. 1992
    ..We concluded that the behaviour of rhodanese is a property inherent to the tissue and not one attained with time...
  83. ncbi Expression of yeast Hem1 gene controlled by Arabidopsis HemA1 promoter improves salt tolerance in Arabidopsis plants
    Zhi Ping Zhang
    Nanjing Agricultural University, China
    BMB Rep 43:330-6. 2010
    ..Therefore, introduction of ALA-S gene led to higher level of ALA metabolism with more salt tolerance in higher plants...
  84. ncbi Toxic effects of arsenic (III) on some hematopoietic and central nervous system variables in rats and guinea pigs
    G M Kannan
    Defense Research and Development Establishment, Gwalior, India
    J Toxicol Clin Toxicol 39:675-82. 2001
    ....
  85. ncbi Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria
    M M Schuurmans
    Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, Switzerland
    Hepatology 33:1217-22. 2001
    ..We conclude that the combined effect of ZnMP on highly induced ALAS and on HO may be of potential benefit for human acute hepatic porphyrias and therefore merits further in vivo investigations addressing questions raised by this study...
  86. ncbi A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia
    H Harigae
    Department of Clinical Medicine, Tohoku University School of Medicine, Sandai, Japan
    Am J Hematol 62:112-4. 1999
    ..These findings suggest that this G663A mutation is responsible for sideroblastic anemia in the proband, and may be an index mutation in this pedigree...
  87. ncbi Mechanism of iron potentiation of hepatic uroporphyria: studies in cultured chick embryo liver cells
    H L Bonkovsky
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322
    Hepatology 10:354-64. 1989
    ..Induction of 5-aminolevulinate synthase amplifies the porphyrin overproduction...
  88. ncbi Thyroid hormone regulation of heme synthesis in rat liver
    T J Smith
    Department of Medicine, State University of New York at Buffalo
    Endocrinology 122:1964-7. 1988
    ..These findings indicate that thyroid status can influence the activity of ALAS, the rate-limiting enzyme in the synthesis of heme in rat liver, as well as heme degradation and the content of cytochrome P450 in this organ...
  89. ncbi Changes of hepatic microsomal oxidative drug metabolizing enzymes in chronic renal failure (CRF) rats by partial nephrectomy
    N Uchida
    Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan
    Jpn J Pharmacol 68:431-9. 1995
    ..These results suggest that CRF states induce not only a reduction of renal function but also an alteration of hepatic metabolism...
  90. ncbi Yeast mutants deficient in heme biosynthesis and a heme mutant additionally blocked in cyclization of 2,3-oxidosqualene
    E G Gollub
    J Biol Chem 252:2846-54. 1977
    ..Supplementation with heme did not remove the requirement for sterol, but it enabled the mutant to convert lanosterol to ergosterol...
  91. ncbi Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome
    D F Bishop
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    Genomics 7:207-14. 1990
    ..Furthermore, the mapping of the ALAS2 gene to the X chromosome and the observed reduction in ALAS activity in X-linked sideroblastic anemia suggest that this disorder may be due to a mutation in the erythroid-specific gene...
  92. ncbi Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females
    M Cazzola
    Department of Hematology, University of Pavia Medical School, Italy
    Blood 96:4363-5. 2000
    ..Blood. 2000;96:4363-4365)..
  93. ncbi Inhibitory effect of AP-1 complex on 5-aminolevulinate synthase gene expression through sequestration of cAMP-response element protein (CRE)-binding protein (CBP) coactivator
    Alejandra S Guberman
    Laboratorio de Biologia Molecular, Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon II Piso 4, Ciudad Universitaria, Argentina
    J Biol Chem 278:2317-26. 2003
    ..We also suggest that the transcriptional properties of this AP-1 site would depend on a spatial-disposition-dependent manner with respect to the CRE sites and to the transcription initiation site...
  94. pmc Heme biosynthesis in mammalian systems: evidence of a Schiff base linkage between the pyridoxal 5'-phosphate cofactor and a lysine residue in 5-aminolevulinate synthase
    G C Ferreira
    Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa 33612
    Protein Sci 2:1959-65. 1993
    ..Mutagenesis of the 5-aminolevulinate synthase residue, which is involved in the Schiff base linkage with pyridoxal 5'-phosphate, from lysine to alanine or histidine abolished enzyme activity in the expressed protein...
  95. ncbi Effects of leaves extract of Ocimum sanctum L. on arsenic-induced toxicity in Wistar albino rats
    G Sharmila Banu
    Centre for Biotechnology, Muthayammal College of Arts and Sciences, Kakkaveri, Rasipuram, Namakkal 637408, Tamilnadu, India
    Food Chem Toxicol 47:490-5. 2009
    ..Further studies thus can be recommended for determining the effect of co-administrating of O. sanctum during chelating therapy with a thiol chelator...
  96. pmc Link between porphyria and fasting uncovered
    David Secko
    CMAJ 173:864. 2005
  97. ncbi Differential regulation of human ALAS1 mRNA and protein levels by heme and cobalt protoporphyrin
    Jianyu Zheng
    Carolinas Medical Center, Charlotte, NC 28203, USA
    Mol Cell Biochem 319:153-61. 2008
    ..These results provide novel insights into the mechanisms of heme repressional effects on ALAS1 and provide a rationale for further investigation of CoPP as a therapeutic agent for acute porphyric syndromes...
  98. ncbi PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle
    Lotte Leick
    Centre of Inflammation and Metabolism, and Copenhagen Muscle Research Centre, Department of Molecular Biology, Institute of Exercise and Sport Sciences, University of Copenhagen, Universitetsparken 13, Copenhagen, Denmark
    Am J Physiol Endocrinol Metab 294:E463-74. 2008
    ..However, PGC-1alpha is not mandatory for training-induced increases in ALAS1, COXI, and cyt c expression, showing that factors other than PGC-1alpha can exert these adaptations...
  99. ncbi Pregnancy and lactation modulate maternal splenic growth and development of the erythroid lineage in the rat and mouse
    Juan J Bustamante
    Institute of Maternal Fetal Biology, University of Kansas Medical Center, Kansas City, KA 66160, USA
    Reprod Fertil Dev 20:303-10. 2008
    ..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...
  100. ncbi Intraspecific variation in expression of candidate genes for osmoregulation, heme biosynthesis and stress resistance suggests local adaptation in European flounder (Platichthys flesus)
    P F Larsen
    Department of Inland Fisheries, Danish Institute for Fisheries Research, Technical University of Denmark, Silkeborg, Denmark
    Heredity (Edinb) 101:247-59. 2008
    ....
  101. pmc GATA transcription factors directly regulate the Parkinson's disease-linked gene alpha-synuclein
    Clemens R Scherzer
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 105:10907-12. 2008
    ..This critical link between GATA factors and SNCA may enable therapies designed to lower alpha-synuclein production...

Research Grants5

  1. GENETICS AND DEVELOPMENT OF ERYTHROID HEME ENZYMES
    Shigeru Sassa; Fiscal Year: 2002
    ..These studies will hopefully clarify the role of ALAS2 and transcription factors such as NF-E2 and Bach1 in erythroid differentiation, and shed light on the distinct aspects of erythroid heme synthesis. ..
  2. Gordon Research Conference on Tetrapyrroles
    Gloria Ferreira; Fiscal Year: 2002
    ..Strengths of this ongoing Gordon conference are its disciplinary diversity, focus on new unpublished work, time for discussion, informal atmosphere, and ban on dissemination of conference proceeding. ..
  3. MECHANISM OF PORPHYRIA CAUSED BY TCDD
    Peter Sinclair; Fiscal Year: 2002
    ..II. To determine whether human CYP1A2 has an essential role in UROgen oxidation and the development of uroporphyria. III. To study the interaction of Fe and CYP1A2 in the development of uroporphyria. ..
  4. Physiology of Malonyl-CoA in Muscle during Exercise
    WILLIAM WINDER; Fiscal Year: 2006
    ..The results will provide additional rationale for the use of regular exercise in preventing and treating type 2 diabetes and obesity. ..
  5. Regulation of Skeletal Muscle LKB1
    WILLIAM WINDER; Fiscal Year: 2010
    ..The proposed studies will provide additional rationale for convincing a predominantly sedentary population of the importance of regular exercise in combating inactivity-related diseases. ..