Fech

Summary

Gene Symbol: Fech
Description: ferrochelatase
Alias: ferrochelatase, mitochondrial
Species: rat
Products:     Fech

Top Publications

  1. Bonkowsky H, Bloomer J, Ebert P, Mahoney M. Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts. J Clin Invest. 1975;56:1139-48 pubmed
    ..This deficiency is probably responsible for protoporphyrin accumulation and hence the biochemical and clinical features observed in protoporphyria. ..
  2. 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. ..
  3. Han A, Fleming M, Chen J. Heme-regulated eIF2alpha kinase modifies the phenotypic severity of murine models of erythropoietic protoporphyria and beta-thalassemia. J Clin Invest. 2005;115:1562-70 pubmed
    ..Our findings also demonstrate that translational regulation could play a critical role in the clinical manifestation of rbc diseases. ..
  4. Sellers V, Johnson M, Dailey H. Function of the [2FE-2S] cluster in mammalian ferrochelatase: a possible role as a nitric oxide sensor. Biochemistry. 1996;35:2699-704 pubmed
    ..The potential physiological relevance of these data to the anemias that are found in individuals with chronic infections is discussed. ..
  5. Henriksson M, Timonen K, Mustajoki P, Pihlaja H, Tenhunen R, Peltonen L, et al. Four novel mutations in the ferrochelatase gene among erythropoietic protoporphyria patients. J Invest Dermatol. 1996;106:346-50 pubmed
  6. Mamet R, Teitz Y, Schoenfeld N. Transformation, growth rate, and the heme biosynthetic pathway in V-abl-transfected fibroblasts. Biochem Med Metab Biol. 1994;52:53-7 pubmed
    ..The relationships between transformation, growth rate, and heme biosynthetic pathway are discussed. ..
  7. Woods J, Fowler B. Effects of chronic arsenic exposure on hematopoietic function in adult mammalian liver. Environ Health Perspect. 1977;19:209-13 pubmed
    ..These changes occur independent of, or prior to, alterations in hepatic hemoprotein-dependent functions and may thus serve in the clinical analysis of pretoxic exposure to arsenic compounds in human populations. ..
  8. Canepa E, Pereda M, Llambias E, Grinstein M. Regulation of phenobarbital-induced ferrochelatase mRNA activity by dibutyryl cAMP and glucose in normal and diabetic rat hepatocytes. Biochem Cell Biol. 1992;70:26-33 pubmed
    ..The results obtained suggest that ferrochelatase is more susceptible to induction with phenobarbital in diabetic rat hepatocytes than in normal rat hepatocytes. ..
  9. Woods J, Fowler B. Alteration of mitochondrial structure and heme biosynthetic parameters in liver and kidney cells by bismuth. Toxicol Appl Pharmacol. 1987;90:274-83 pubmed
    ..These findings are comparable to those previously reported of other trace metals with known toxicologic potential and may represent early events in bismuth-induced cell injury. ..

More Information

Publications33

  1. Shanker J, Datta K. Excess generation of endogenous heme inhibits L-alanine:4,5-dioxovalerate transaminase in rat liver mitochondria. Biochem Biophys Res Commun. 1986;138:751-7 pubmed
  2. 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
  3. Franco R, Bai G, Prosinecki V, Abrunhosa F, Ferreira G, Bastos M. Porphyrin-substrate binding to murine ferrochelatase: effect on the thermal stability of the enzyme. Biochem J. 2005;386:599-605 pubmed
    ..However, in contrast with the wild-type enzyme, the thermal denaturation of ferrochelatase variants was best described as a non-co-operative denaturation process. ..
  4. Rios de Molina M, Mazzetti M, Galigniana M, Aldonatti C, Tomio J, San Martin de Viale L. The decrease in uroporphyrinogen decarboxylase activity induced by ethanol predisposes rats to the development of porphyria and accelerates xenobiotic-triggered porphyria, regardless of hepatic damage. Braz J Med Biol Res. 2002;35:1273-83 pubmed
  5. Magness S, Maeda N, Brenner D. An exon 10 deletion in the mouse ferrochelatase gene has a dominant-negative effect and causes mild protoporphyria. Blood. 2002;100:1470-7 pubmed
    ..Heterozygous mice exhibited skin photosensitivity but no liver disease. These results lend support for a dominant-negative effect of a mutant allele on ferrochelatase activity in patients with protoporphyria. ..
  6. Bloks V, Plosch T, van Goor H, Roelofsen H, Baller J, Havinga R, et al. Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice. J Lipid Res. 2001;42:41-50 pubmed
    ..Roelofsen, J. Baller, R. Havinga, H. J. Verkade, A. van Tol, P. L. M. Jansen, and F. Kuipers. Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice. J. Lipid Res. 2001. 42: 41;-50. ..
  7. Tutois S, Montagutelli X, Da Silva V, Jouault H, Rouyer Fessard P, Leroy Viard K, et al. Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease. J Clin Invest. 1991;88:1730-6 pubmed
    ..Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. ..
  8. White C, Yuan X, Schmidt P, Bresciani E, Samuel T, Campagna D, et al. HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. Cell Metab. 2013;17:261-70 pubmed publisher
    ..Our results reveal HRG1 as the long-sought heme transporter for heme-iron recycling in macrophages and suggest that genetic variations in HRG1 could be modifiers of human iron metabolism. ..
  9. Jollie D, Maines M. Effect of cis-platinum on kidney cytochrome P-450 and heme metabolism: evidence for the regulatory role of the pituitary hormones. Arch Biochem Biophys. 1985;240:51-9 pubmed
    ..This, in turn, could increase the production of cytochrome P-450. It is suggested that the anterior pituitary hormones control the concentration of the cytochrome P-450 in the kidney, and this process may be interrupted by cis-platinum. ..
  10. Woods J, Fowler B. Metal alteration of uroporphyrinogen decarboxylase and coproporphyrinogen oxidase. Ann N Y Acad Sci. 1987;514:55-64 pubmed
    ..Advantage might be taken of such chemical- and organ-specific changes in porphyrin metabolism and porphyrin excretion patterns in monitoring prolonged, subclinical exposure to such chemicals in human populations. ..
  11. Crouse B, Sellers V, Finnegan M, Dailey H, Johnson M. Site-directed mutagenesis and spectroscopic characterization of human ferrochelatase: identification of residues coordinating the [2Fe-2S] cluster. Biochemistry. 1996;35:16222-9 pubmed
    ..Such anomalous coordination could account for the cluster lability compared to similar clusters with complete cysteinyl ligation and hence may be intrinsic to the proposed regulatory role for this cluster in mammalian ferrochelatases. ..
  12. Nagai M, Nagai T, Yamamoto M, Goto K, Bishop T, Hayashi N, et al. Novel regulation of delta-aminolevulinate synthase in the rat harderian gland. Biochem Pharmacol. 1997;53:643-50 pubmed
    ..The constitutive expression of the ALAS-N gene in the Harderian gland suggests a novel transcriptional control mechanism of this gene. ..
  13. Boulechfar S, Lamoril J, Montagutelli X, Guenet J, Deybach J, Nordmann Y, et al. Ferrochelatase structural mutant (Fechm1Pas) in the house mouse. Genomics. 1993;16:645-8 pubmed
    ..This Fechm1Pas/Fechm1Pas mutant mouse represents a useful model for studying the pathophysiological feature of the human disease and the first accessible model for gene therapy in the field of porphyrias. ..
  14. Lyoumi S, Abitbol M, Andrieu V, Henin D, Robert E, Schmitt C, et al. Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice. Blood. 2007;109:811-8 pubmed
    Patients with deficiency in ferrochelatase (FECH), the last enzyme of the heme biosynthetic pathway, experience a painful type of skin photosensitivity called erythropoietic protoporphyria (EPP), which is caused by the excessive ..
  15. Wainstok de Calmanovici R, Rios de Molina M, Taira de Yamasato M, Tomio J, San Martin de Viale L. Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment. Biochem J. 1984;218:753-63 pubmed
    ..Of the several hypotheses that could explain the action of HCB on the haem pathway, our results would suggest that the porphyrinogenic action of HCB is mediated by some of its metabolic products. ..
  16. Shi Z, Ferreira G. Probing the active site loop motif of murine ferrochelatase by random mutagenesis. J Biol Chem. 2004;279:19977-86 pubmed
    ..However, despite the plasticity of the loop primary structure, the relative spatial positioning of the loop in the active site appeared to be maintained in functional variants, supporting a role for the loop in ferrochelatase function. ..
  17. Yoon T, Cowan J. Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis. J Biol Chem. 2004;279:25943-6 pubmed
  18. Oskarsson A, Fowler B. Effects of lead on the heme biosynthetic pathway in rat kidney. Exp Mol Pathol. 1985;43:409-17 pubmed
    ..These data also suggest that the observed increases in urinary porphyrin excretion are primarily due to lead effects on the erythropoietic system. ..
  19. Chernova T, Nicotera P, Smith A. Heme deficiency is associated with senescence and causes suppression of N-methyl-D-aspartate receptor subunits expression in primary cortical neurons. Mol Pharmacol. 2006;69:697-705 pubmed
    ..Culture of cortical neurons from BALB/c Fech(m1Pas) mutant mice demonstrating depressed heme synthesis showed premature senescence and reduced expression of ..
  20. Magness S, Brenner D. Targeted disruption of the mouse ferrochelatase gene producing an exon 10 deletion. Biochim Biophys Acta. 1999;1453:161-74 pubmed
    ..This suggests that requirement of an additional mutation to decrease the expression of the wild-type allele. ..
  21. Shi Z, Franco R, Haddad R, Shelnutt J, Ferreira G. The conserved active-site loop residues of ferrochelatase induce porphyrin conformational changes necessary for catalysis. Biochemistry. 2006;45:2904-12 pubmed
    ..These results suggest that specific conserved loop residues (especially Trp256) are directly involved in the saddling of the porphyrin substrate. ..
  22. Ferreira G. Ferrochelatase binds the iron-responsive element present in the erythroid 5-aminolevulinate synthase mRNA. Biochem Biophys Res Commun. 1995;214:875-8 pubmed
    ..This IRE-binding activity of ferrochelatase may play a critical role in the regulation of heme biosynthesis in differentiating erythrocytes. ..
  23. Nichol A, Elsbury S, Angel L, Elder G. The site of inhibition of porphyrin biosynthesis by an isomer of diazinon in rats. Biochem Pharmacol. 1983;32:2653-7 pubmed
  24. Abraham N, Camadro J, Hoffstein S, Levere R. Effects of iron deficiency and chronic iron overloading on mitochondrial heme biosynthetic enzymes in rat liver. Biochim Biophys Acta. 1986;870:339-49 pubmed
    ..The mitochondrial heme content was also decreased by 40% in iron-overloaded rats but unchanged in either iron-deficient or control rats. ..