5 aminolevulinate synthetase


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

Top Publications

  1. Marcus D, Nadel H, Lew G, Freedman M. Cimetidine suppresses chemically induced experimental hepatic porphyria. Am J Med Sci. 1990;300:214-7 pubmed
    ..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...
  2. Caballero F, Gerez E, Oliveri L, Falcoff N, Batlle A, Vazquez E. On the promoting action of tamoxifen in a model of hepatocarcinogenesis induced by p-dimethylaminoazobenzene in CF1 mice. Int J Biochem Cell Biol. 2001;33:681-90 pubmed
    ..To document the long-term effect of TMX in mice treated with p-dimethylaminoazobenzene (DAB), we have investigated the time response action of these drugs on different biochemical parameters...
  3. Ihara N, Akagi R, Ejiri K, Kudo T, Furuyama K, Fujita H. Developmental changes of gene expression in heme metabolic enzymes in rat placenta. FEBS Lett. 1998;439:163-7 pubmed
    ..Induced acute fetal hypoxia resulted in an increase in ALAS-N mRNA and in a decrease in HO-1 mRNA. These findings indicate that placental heme metabolism is influenced by the oxygen supply. ..
  4. Li D. PGC-1alpha: looking behind the sweet treat for porphyria. Cell. 2005;122:487-9 pubmed
    ..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. ..
  5. Han L, Lu J, Pan L, Wang X, Shao Y, Han S, et al. Histone acetyltransferase p300 regulates the transcription of human erythroid-specific 5-aminolevulinate synthase gene. Biochem Biophys Res Commun. 2006;348:799-806 pubmed
    ..Meanwhile, this work identified that ALAS2 is a novel target gene for p300/CBP action as histone acetyltransferases. ..
  6. Han L, Zhong Y, Huang B, Han L, Pan L, Xu X, et al. Sodium butyrate activates erythroid-specific 5-aminolevulinate synthase gene through Sp1 elements at its promoter. Blood Cells Mol Dis. 2008;41:148-53 pubmed publisher
    ..Also, our data suggested that HDAC1 may be a target enzyme of NaBu action. ..
  7. Buzaleh A, Moran Jimenez M, Garcia Bravo M, Sampedro A, Batlle A, Enriquez De Salamanca R, et al. Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria. Cell Mol Biol (Noisy-le-grand). 2009;55:38-44 pubmed
    ..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. ..
  8. Cole R, Garlick J, Cheek E. Activities of haem synthetic enzymes in blood cells of pre-natal flexed-tailed (f/f) anaemic mice. J Embryol Exp Morphol. 1975;34:373-86 pubmed
  9. Tanaka E, Kurata N, Kohno M, Yoshida T, Kuroiwa Y. Induction of cytochrome P-450 and related drug-oxidizing activities in muscone (3-methylcyclopentadecanone)-treated rats. Biochem Pharmacol. 1987;36:4263-7 pubmed
    ..This type of induction of the hepatic metabolizing enzymes was similar to that seen after treatment with a prototype drug, phenobarbital. ..

More Information

Publications107 found, 100 shown here

  1. Xie L, Hall D, Eiteman M, Altman E. Optimization of recombinant aminolevulinate synthase production in Escherichia coli using factorial design. Appl Microbiol Biotechnol. 2003;63:267-73 pubmed
    ..Based on the full factorial design results, a fermentation was completed that yielded 296 mU/mg protein with a final ALA concentration of 5.2 g/l (39 mM). ..
  2. Whatley S, Mason N, Holme S, Anstey A, Elder G, Badminton M. Molecular epidemiology of erythropoietic protoporphyria in the U.K. Br J Dermatol. 2010;162:642-6 pubmed publisher
    ..These data define the prevalence and molecular epidemiology of each type of EPP in the U.K. ..
  3. Pascoe G, Correia M. Role of gastrin/pentagastrin in regulation of intestinal cytochrome P-450. Comp Biochem Physiol C. 1988;90:41-6 pubmed
    ..4. The intestinal trophic peptide hormone, gastrin, apparently does not regulate the cytochrome P-450-dependent MFO system of the small intestine. ..
  4. Koc S, Harris J. Sideroblastic anemias: variations on imprecision in diagnostic criteria, proposal for an extended classification of sideroblastic anemias. Am J Hematol. 1998;57:1-6 pubmed
    ..We recommend a more precise evaluation and documentation of the components that characterize the sideroblastic abnormality and propose an extended classification of the sideroblastic anemias. ..
  5. Kramer M, Gunaratne P, Ferreira G. Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene. Gene. 2000;247:153-66 pubmed
    ..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. ..
  6. Kannan G, Tripathi N, Dube S, Gupta M, Flora S. Toxic effects of arsenic (III) on some hematopoietic and central nervous system variables in rats and guinea pigs. J Toxicol Clin Toxicol. 2001;39:675-82 pubmed
    ..At low doses (10 and 25 ppm in drinking water), the effects of arsenic on hematopoietic indices and whole-brain neurotransmitter concentrations were more prominent in guinea pigs than in rats with some variability in the dose response. ..
  7. Cheltsov A, Guida W, Ferreira G. Circular permutation of 5-aminolevulinate synthase: effect on folding, conformational stability, and structure. J Biol Chem. 2003;278:27945-55 pubmed
    ..We propose that the order of the ALAS secondary structure elements does not determine the ability of the polypeptide chain to fold but does affect its folding mechanism. ..
  8. Barton J, Lee P. Disparate phenotypic expression of ALAS2 R452H (nt 1407 G --> A) in two brothers, one with severe sideroblastic anemia and iron overload, hepatic cirrhosis, and hepatocellular carcinoma. Blood Cells Mol Dis. 2006;36:342-6 pubmed
    ..Possible explanations for the disparate red blood cell and iron phenotypes of the proband and his family members are discussed. ..
  9. Hunter G, Zhang J, Ferreira G. Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. J Biol Chem. 2007;282:23025-35 pubmed
    ..The data support important refinements to both the chemical and kinetic mechanisms and indicate that 5-aminolevulinate synthase operates under the stereoelectronic control predicted by Dunathan's hypothesis. ..
  10. Peyer A, Jung D, Beer M, Gnerre C, Keogh A, Stroka D, et al. Regulation of human liver delta-aminolevulinic acid synthase by bile acids. Hepatology. 2007;46:1960-70 pubmed
    ..These data also suggest that elevated endogenous bile acids may precipitate neuropsychiatric attacks in patients with acute hepatic porphyrias. ..
  11. Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. Br J Haematol. 2008;143:27-38 pubmed publisher
    ..Local mitochondrial iron overload is present in all sideroblastic anaemias, whereas systemic iron overload occurs only in the forms because of primary or secondary deficiency of ALAS2. ..
  12. Vlaski M, Lafarge X, Chevaleyre J, Duchez P, Boiron J, Ivanovic Z. 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. Exp Hematol. 2009;37:573-84 pubmed publisher
    ..These results imply that integral regulation of erythropoiesis is operated by low O(2) concentrations, beyond the EPO/EPO-responsive cells loop and provide a tool to optimize the technology for ex vivo production of RBC. ..
  13. Miranda C, Henderson M, Wang J, Nakaue H, Buhler D. Comparative effects of the polychlorinated biphenyl mixture, Aroclor 1242, on porphyrin and xenobiotic metabolism in kidney of Japanese quail and rat. Comp Biochem Physiol C. 1992;103:149-52 pubmed
    ..4. Renal ethoxyresorufin O-deethylase activity was induced in rat and quail whereas renal ethoxycoumarin O-deethylase and glutathione S-transferase activities were induced only in rats by Aroclor 1242. ..
  14. Kurata N, Yoshida T, Kuroiwa Y, Masuko T, Hashimoto Y. Long-term effects of phenobarbital on rat liver microsomal drug-metabolizing enzymes and heme-metabolizing enzyme. Res Commun Chem Pathol Pharmacol. 1989;65:161-79 pubmed
    ..On the other hand, biological half-lives of microsomal drug-metabolizing enzymes were longer in the tolerant group than in the dependent group. ..
  15. Schuurmans M, Hoffmann F, Lindberg R, Meyer U. Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria. Hepatology. 2001;33:1217-22 pubmed
    ..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. ..
  16. Cazzola M, May A, Bergamaschi G, Cerani P, Ferrillo S, Bishop D. Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. Blood. 2002;100:4236-8 pubmed
    ..This observation is relevant to genetic counseling, emphasizing the importance of gene-based diagnosis. ..
  17. Cortesão E, Vidan J, Pereira J, Gonçalves P, Ribeiro M, Tamagnini G. Onset of X-linked sideroblastic anemia in the fourth decade. Haematologica. 2004;89:1261-3 pubmed
    ..On presentation she had macrocytic anemia with severe iron overload. ..
  18. Piao Y, Kiatpapan P, Yamashita M, Murooka Y. Effects of expression of hemA and hemB genes on production of porphyrin in Propionibacterium freudenreichii. Appl Environ Microbiol. 2004;70:7561-6 pubmed
  19. Buzaleh A, Batlle A. Glutathione depletion and anaesthesia in mice alter heme and drug metabolising enzymes. Biochim Biophys Acta. 2005;1723:128-34 pubmed
  20. 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
    ..The present study provides evidence that ALAS2 is broken down under normoxic conditions by the proteasome and that the prolyl-4-hydroxylase/vHL E3 ubiquitin ligase pathway may be involved. ..
  21. Xiaoxia L, Jianping L, Peilin C. Effect of inducers on the production of 5-aminolevulinic acid by recombinant Escherichia coli. Prep Biochem Biotechnol. 2006;36:223-33 pubmed
    ..When lactose concentration was 5 mmol/L, the specific ALA synthase activity and ALA productivity reached 16.7 nmol/(min . mg of protein) and 1.15 g/L, respectively, which were about 15% and 43% higher than those induced by IPTG. ..
  22. Canepa E, Llambias E, Grinstein M. Studies on induction of delta-aminolevulinic acid synthase, ferrochelatase, cytochrome P-450 and cyclic AMP by phenformin. Chlorpropamide, allylisopropylacetamide and lead in hepatocytes from normal and experimental diabetic rats. Biochem Pharmacol. 1990;40:365-72 pubmed
    ..The present results add more experimental evidence about the lability of the heme pathway of diabetic hepatocytes...
  23. Elliott W, May B, Bawden M, Hansen A. Regulation of genes associated with drug metabolism. Biochem Soc Symp. 1989;55:13-27 pubmed
    ..Studies on the drug-induction mechanism of phenobarbital-inducible P-450s in chick embryo liver show that increased mRNA levels result from P-450 gene activation together with a significant post-transcriptional mechanism...
  24. Zenke M, Kahn P, Disela C, Vennstrom B, Leutz A, Keegan K, et al. v-erbA specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene. Cell. 1988;52:107-19 pubmed
    ..Additional evidence obtained with an inhibitor of band 3 activity suggests that the v-erbA-induced inhibition of band 3 gene expression is at least partly responsible for the differentiation block caused by this oncogene. ..
  25. Shah S, McGadey J, Moore M, Houston T, Payne A. The effects of bromocriptine and prolactin on porphyrin biosynthesis and morphology in the female hamster harderian gland. J Comp Physiol B. 1996;166:144-9 pubmed
    ..The results support the hypothesis that while androgens have an inhibitory effect on porphyrin synthesis within this model, prolactin may have a major facilitatory role. ..
  26. Surinya K, Cox T, May B. Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene. J Biol Chem. 1998;273:16798-809 pubmed
  27. 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
    ..Blood. 2000;96:4363-4365) ..
  28. Tomas Zapico C, Martínez Fraga J, Rodríguez Colunga M, Tolivia D, Hardeland R, Coto Montes A. Melatonin protects against delta-aminolevulinic acid-induced oxidative damage in male Syrian hamster Harderian glands. Int J Biochem Cell Biol. 2002;34:544-53 pubmed
    ..These results suggest that melatonin may have profound effects on the oxidant status of the Harderian gland. ..
  29. Laftah A, Raja K, Simpson R, Peters T. Effect of Tin-mesoporphyrin, an inhibitor of haem catabolism, on intestinal iron absorption. Br J Haematol. 2003;122:298-304 pubmed
    ..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. ..
  30. Bishop D, Henderson A, Astrin K. Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome. Genomics. 1990;7:207-14 pubmed
    ..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. ..
  31. Afonso S, Polo C, Navone N, Vazquez E, Buzaleh A, Schoua E, et al. In vivo prevention and reversal by the antimitotic colchicine and other related compounds of some porphyrinogenic drug action on heme pathway. Gen Pharmacol. 1990;21:423-6 pubmed
    ..4. The usefulness of the combination of the in vivo experimental model and the in vitro explant tissue culture model, for this kind of studies is emphasized...
  32. May B, Hansen A. Effect of haem on cytochrome P-450 synthesis. Clin Exp Pharmacol Physiol. 1989;16:497-500 pubmed
    ..The work does not provide evidence for the suggestion that haem is required for cytochrome P-450 gene transcription...
  33. Leong S, Williams P, Ditta G. Analysis of the 5' regulatory region of the gene for delta-aminolevulinic acid synthetase of Rhizobium meliloti. Nucleic Acids Res. 1985;13:5965-76 pubmed
    ..coli promoter sequence, while the -10 region is dissimilar. No resemblance was found between either P1 or P2 and the promoter regions of genes under general nitrogen control...
  34. Vazquez E, Buzaleh A, Wider E, Batlle A. Red blood cell rhodanese: its possible role in modulating delta-aminolaevulinate synthetase activity in mammals. Int J Biochem. 1987;19:217-9 pubmed
    ..It is suggested that a similar scheme, to that proposed for the control of ALA-S in Rhodopseudomonas spheroides and soybean callus, is also operating in animals. ..
  35. 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
  36. Sivaprasad T, Malarkodi S, Varalakshmi P. Therapeutic efficacy of lipoic acid in combination with dimercaptosuccinic acid against lead-induced renal tubular defects and on isolated brush-border enzyme activities. Chem Biol Interact. 2004;147:259-71 pubmed
    ..Relative to the administration of lead, the combined therapy showed betterment on the renal integrity with respect to the functional parameters assessed, thereby indicating its efficacy over the monotherapies. ..
  37. Secko D. Link between porphyria and fasting uncovered. CMAJ. 2005;173:864 pubmed
  38. Schulze J, Schubert W, Moser J, Jahn D, Heinz D. Evolutionary relationship between initial enzymes of tetrapyrrole biosynthesis. J Mol Biol. 2006;358:1212-20 pubmed publisher
    ..We thus propose that the CoA-subfamily (including ALAS) and the aminotransferase subfamily II (including GSAM) are evolutionarily closely related and that ALAS may thus have evolved from GSAM...
  39. Leick L, Wojtaszewski J, Johansen S, Kiilerich K, Comes G, Hellsten Y, et al. PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2008;294:E463-74 pubmed
    ..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. ..
  40. Riddle R, Yamamoto M, Engel J. Expression of delta-aminolevulinate synthase in avian cells: separate genes encode erythroid-specific and nonspecific isozymes. Proc Natl Acad Sci U S A. 1989;86:792-6 pubmed
  41. Verderber E, Lucast L, Van Dehy J, Cozart P, Etter J, Best E. Role of the hemA gene product and delta-aminolevulinic acid in regulation of Escherichia coli heme synthesis. J Bacteriol. 1997;179:4583-90 pubmed
    ..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. ..
  42. Roberts A, Elder G. Alternative splicing and tissue-specific transcription of human and rodent ubiquitous 5-aminolevulinate synthase (ALAS1) genes. Biochim Biophys Acta. 2001;1518:95-105 pubmed
  43. Fujii H, Takahashi T, Matsumi M, Kaku R, Shimizu H, Yokoyama M, et al. Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure. Int J Mol Med. 2004;14:1001-5 pubmed
  44. Hofer M, Duchene M. Entamoeba histolytica: construction and applications of subgenomic databases. Exp Parasitol. 2005;110:178-83 pubmed
    ..This procedure revealed that some E. histolytica genes may have several putative functions. Representative examples such as the case of the delta-aminolevulinate synthase/serine palmitoyltransferase are discussed. ..
  45. Furuyama K, Harigae H, Heller T, Hamel B, Minder E, Shimizu T, et al. Arg452 substitution of the erythroid-specific 5-aminolaevulinate synthase, a hot spot mutation in X-linked sideroblastic anaemia, does not itself affect enzyme activity. Eur J Haematol. 2006;76:33-41 pubmed
  46. Kumar N, Solt L, Wang Y, Rogers P, Bhattacharyya G, Kamenecka T, et al. Regulation of adipogenesis by natural and synthetic REV-ERB ligands. Endocrinology. 2010;151:3015-25 pubmed publisher
    ..Moreover, synthetic small molecule ligands for REV-ERB are effective modulators of adipogenesis and may be useful for treatment of metabolic diseases. ..
  47. May A, Bishop D. The molecular biology and pyridoxine responsiveness of X-linked sideroblastic anaemia. Haematologica. 1998;83:56-70 pubmed
    ..The next few years of investigation should be illuminating as tools now exist to study all aspects of this protein from the gene to the mitochondrial matrix. ..
  48. Zhang J, Ferreira G. Transient state kinetic investigation of 5-aminolevulinate synthase reaction mechanism. J Biol Chem. 2002;277:44660-9 pubmed
    ..Finally, the carbonyl and carboxylate groups of 5-aminolevulinate play a major protein-interacting role by inducing a conformational change in ALAS and, thus, possibly modulating product release. ..
  49. Kaliman P, Inshina N, Strel chenko E. [Activity of key enzymes of heme metabolism and cytochrome P-450 content in the rat liver in experimental rhabdomyolysis and hemolytic anemia]. Ukr Biokhim Zh (1999). 2003;75:109-14 pubmed
    ..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. ..
  50. Petricek M, Petrickova K, Havlicek L, Felsberg J. Occurrence of two 5-aminolevulinate biosynthetic pathways in Streptomyces nodosus subsp. asukaensis is linked with the production of asukamycin. J Bacteriol. 2006;188:5113-23 pubmed
    ..The hemA-asuA gene is situated within a putative cluster of asukamycin biosynthetic genes. This is the first report about the cloning of genes for two different ALA biosynthetic routes from a single bacterium. ..
  51. He X, Zhou J, Cheng Y, Fan J. [Purification and production of the extracellular 5-aminolevulinate from recombiniant Escherichia coli expressing yeast ALAS]. Sheng Wu Gong Cheng Xue Bao. 2007;23:520-4 pubmed
    ..5 with exogenous levulinate, succinate and and glycine at the concentration of 20 mmol/L respectively. The purity of ALA after purification is up to 90%. ..
  52. Zhu J, Park C, Sjeklocha L, Kren B, Steer C. High-level genomic integration, epigenetic changes, and expression of sleeping beauty transgene. Biochemistry. 2010;49:1507-21 pubmed publisher
    ..In addition, long-range activation of host genes must now be recognized as a potential consequence of an inserted transgene cassette containing enhancer elements. ..
  53. Fuerstenberg S, Leitner I, Schroeder C, Schwarz H, Vennstrom B, Beug H. Transcriptional repression of band 3 and CAII in v-erbA transformed erythroblasts accounts for an important part of the leukaemic phenotype. EMBO J. 1992;11:3355-65 pubmed
  54. Cable E, Cable J, Bonkovsky H. Repression of hepatic delta-aminolevulinate synthase by heme and metalloporphyrins: relationship to inhibition of heme oxygenase. Hepatology. 1993;18:119-27 pubmed
    ..This result suggests that the repressive effect of heme is directed toward decreasing synthesis, increasing breakdown or decreasing the translation of the messenger RNA of delta-aminolevulinate synthase.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  55. Bekri S, May A, Cotter P, Al Sabah A, Guo X, Masters G, et al. A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. Blood. 2003;102:698-704 pubmed
    ..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. ..
  56. Dzikaite V, Hultcrantz R, Melefors O. The regulatory effect of heme on erythroid aminolevulinate synthase in natural erythroid cells. Biochim Biophys Acta. 2003;1630:19-24 pubmed
    ..Heme formation seems to be more tightly controlled in the bone marrow (nucleated) cells in order to prevent oxidative cell damage, compared to more differentiated erythroid cells. ..
  57. Zhang D, CHENG F, Cheng J, Zhang Z, Liu Y. [Cloning and prokaryotic expression of Rhodoblastus acidophilus 5-aminolevlinate synthase gene]. Wei Sheng Wu Xue Bao. 2007;47:639-44 pubmed
    ..Our recombinant bacteria are of great potential in the production of ALA. Our results offer an easy and simple ALA mass production method and may stimulate the application of ALA in agriculture...
  58. 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. ..
  59. Fu W, Lin J, Cen P. Expression of a hemA gene from Agrobacterium radiobacter in a rare codon optimizing Escherichia coli for improving 5-aminolevulinate production. Appl Biochem Biotechnol. 2010;160:456-66 pubmed publisher
    ..Based on an optimal fed-batch culture system described in our previous work, up to 6.5 g/l (50 mM) ALA was produced in a 15-l fermenter. ..
  60. Cochón A, San Martin de Viale L, Wainstok de Calmanovici R. Cyclophosphamide and its metabolite acrolein. Some studies on their porphyrinogenic action in 17 day old chick embryo. Comp Biochem Physiol C. 1992;102:143-8 pubmed
  61. Mamet R, Schoenfeld N, Mevasser R, Bomstein Y, Lahav M, Atsmon A. Regulation of heme synthesis in the regenerating rat liver. Biochem Med Metab Biol. 1990;43:263-70 pubmed
    ..The decrease observed in the activity of cytosolic ALAS might be due to impaired synthesis of the enzyme but does not affect the regulation of the heme biosynthetic pathway...
  62. Drew P, Ades I. Regulation of production of delta-aminolaevulinate synthase in tissues of chick embryos. Effects of porphyrogenic agents and of haem precursors. Biochem J. 1989;262:815-21 pubmed
  63. Otsuka A, Buoncristiani M, Howard P, Flamm J, Johnson C, Yamamoto R, et al. The Escherichia coli biotin biosynthetic enzyme sequences predicted from the nucleotide sequence of the bio operon. J Biol Chem. 1988;263:19577-85 pubmed
    ..The product of the bioF gene, 7-keto-8-aminopelargonic acid synthetase, was found to be similar to 5-aminolevulinic acid synthetase. ..
  64. Bonkovsky H, Lincoln B, Healey J, Ou L, Sinclair P, Muller Eberhard U. Hepatic heme and drug metabolism in rats with chronic mountain sickness. Am J Physiol. 1986;251:G467-74 pubmed
    ..Thus the oxygen-requiring processes of hepatic heme and drug metabolism were well maintained despite chronic profound hypoxia sufficient to cause cardiopulmonary complications...
  65. El Missiry M. Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats. J Biochem Mol Toxicol. 2000;14:57-62 pubmed
    ..The action of melatonin on lead-induced changes was attributed to protection of the antioxidant capacity in cells in addition to the ability of melatonin to scavenge free radicals. ..
  66. Roberts A, Redding S, Llewellyn D. An alternatively-spliced exon in the 5'-UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem-mediated decay. FEBS Lett. 2005;579:1061-6 pubmed
    ..These data suggest that translation of ALAS1 mRNA itself might be required for destabilisation in response to haem. ..
  67. Kaliman P, Barannik T, Strel chenko E, Inshina N, Sokol O. Intracellular redistribution of heme in rat liver under oxidative stress: the role of heme synthesis. Cell Biol Int. 2005;29:9-14 pubmed
    ..Thus heme synthesis can greatly contribute to heme intracellular redistribution under oxidative stress. ..
  68. Phillips J, Kushner J. Fast track to the porphyrias. Nat Med. 2005;11:1049-50 pubmed
  69. Solomon P, Jörgens C, Oliver R. Delta-aminolaevulinic acid synthesis is required for virulence of the wheat pathogen Stagonospora nodorum. Microbiology. 2006;152:1533-8 pubmed
    ..This study has identified a key role for fungal ALA synthesis during infection and revealed its potential as an antifungal target. ..
  70. Aivado M, Gattermann N, Rong A, Giagounidis A, Prall W, Czibere A, et al. X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. Blood Cells Mol Dis. 2006;37:40-5 pubmed
    ..The features of the disorder in this family are also instructive in regard to the differential diagnosis of sideroblastic anemias in women. ..
  71. Yasuda Y, Sasaki T, Takagawa M, Maeda M, Yasuda M, Atsumi T, et al. Erythropoietin contributes to implantation: ectopic hemoglobin synthesis in decidual cells of mice. Congenit Anom (Kyoto). 2007;47:22-33 pubmed
    ..This is the first evidence that ectopic Hb synthesis exists and that erythropoietin coregulates erythroid (globin) and nonerythroid (delta-aminolevulinate synthase) genes. ..
  72. Wang H, Zhou Q, Kesinger J, Norris C, Valdez C. Heme regulates exocrine peptidase precursor genes in zebrafish. Exp Biol Med (Maywood). 2007;232:1170-80 pubmed
    ..Our findings provide a better understanding of heme deficiency pathogenesis and enhance our ability to diagnose and treat patients with porphyria or pancreatic diseases. ..
  73. Navone N, Vazquez E, Polo C, Batlle A. Rhodanese and ALA-S in mammary tumor and liver from normal and tumor-bearing mice. Comp Biochem Physiol B. 1992;102:83-5 pubmed
    ..We concluded that the behaviour of rhodanese is a property inherent to the tissue and not one attained with time...
  74. Wainstok de Calmanovici R, Cochón A, Aldonatti C, Cabral J, San Martin de Viale L. Sex comparison of heme pathway in rats bearing hepatic tumors. Tumori. 1991;77:379-84 pubmed
    ..e) The heme pathway was functional in DENA induced tumors in both male and female rats but they were little affected by HCB. ..
  75. 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. ..
  76. Ojuka E, Jones T, Han D, Chen M, Wamhoff B, Sturek M, et al. Intermittent increases in cytosolic Ca2+ stimulate mitochondrial biogenesis in muscle cells. Am J Physiol Endocrinol Metab. 2002;283:E1040-5 pubmed
    ..These findings provide evidence that intermittently raising cytosolic Ca2+ stimulates mitochondrial biogenesis in muscle cells. ..
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