Ferrochelatase

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Ferrochelatase (protoporphyria)
PDB rendering based on 1hrk.
Available structures: 1hrk, 2hrc, 2hre
Identifiers
Symbol(s) FECH; EPP; FCE
External IDs OMIM: 177000 MGI: 95513 HomoloGene: 113
EC number 4.99.1.1
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 2235 14151
Ensembl ENSG00000066926 ENSMUSG00000024588
Uniprot P22830 Q3UC49
Refseq NM_000140 (mRNA)
NP_000131 (protein)		 XM_001000060 (mRNA)
XP_001000060 (protein)
Location Chr 18: 53.37 - 53.4 Mb Chr 18: 64.58 - 64.61 Mb
Pubmed search [1] [2]

Ferrochelatase (FECH, protoheme ferrolyase) is an enzyme that catalyses the terminal (eighth) step in the biosynthesis of heme, converting protoporphyrin IX into heme. It catalyses reaction: protoporphyrin + Fe++ ↔ protoheme + 2 H+. A ferrochelatase enzyme consists of 497 amino acid residues with a m.w. of 55.4 kDa.[1]

Ferrochelatase is localized to the mitochondrion where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Defects in ferrochelatase are associated with erythropoietic protoporphyria. Two transcript variants encoding different isoforms have been found for this gene.[1]

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Contents

[edit] See also

[edit] References

  1. ^ a b Entrez Gene: FECH ferrochelatase (protoporphyria).

[edit] Further reading

  • Cox TM (1997). "Erythropoietic protoporphyria.". J. Inherit. Metab. Dis. 20 (2): 258–69. PMID 9211198. 
  • Buller RE, Schrader WT, O'Maller BW (1976). "Steroids and the practical aspects of performing binding studies.". J. Steroid Biochem. 7 (5): 321–6. PMID 180343. 
  • Bonkowsky HL, Bloomer JR, Ebert PS, Mahoney MJ (1976). "Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts.". J. Clin. Invest. 56 (5): 1139–48. PMID 1184741. 
  • Brenner DA, Didier JM, Frasier F, et al. (1992). "A molecular defect in human protoporphyria.". Am. J. Hum. Genet. 50 (6): 1203–10. PMID 1376018. 
  • Nakahashi Y, Fujita H, Taketani S, et al. (1992). "The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria.". Proc. Natl. Acad. Sci. U.S.A. 89 (1): 281–5. PMID 1729699. 
  • Lamoril J, Boulechfar S, de Verneuil H, et al. (1992). "Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene.". Biochem. Biophys. Res. Commun. 181 (2): 594–9. PMID 1755842. 
  • Diep A, Li C, Klisak I, et al. (1992). "Assignment of the gene for cyclic AMP-response element binding protein 2 (CREB2) to human chromosome 2q24.1-q32.". Genomics 11 (4): 1161–3. PMID 1838349. 
  • Nakahashi Y, Taketani S, Okuda M, et al. (1991). "Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase.". Biochem. Biophys. Res. Commun. 173 (2): 748–55. PMID 2260980. 
  • Rossi E, Attwood PV, Garcia-Webb P, Costin KA (1990). "Inhibition of human lymphocyte ferrochelatase activity by hemin.". Biochim. Biophys. Acta 1038 (3): 375–81. PMID 2340297. 
  • Polson RJ, Lim CK, Rolles K, et al. (1988). "The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria.". Transplantation 46 (3): 386–9. PMID 3047929. 
  • Bonkovsky HL, Schned AR (1986). "Fatal liver failure in protoporphyria. Synergism between ethanol excess and the genetic defect.". Gastroenterology 90 (1): 191–201. PMID 3940245. 
  • Prasad AR, Dailey HA (1995). "Effect of cellular location on the function of ferrochelatase.". J. Biol. Chem. 270 (31): 18198–200. PMID 7629135. 
  • Sarkany RP, Alexander GJ, Cox TM (1994). "Recessive inheritance of erythropoietic protoporphyria with liver failure.". Lancet 343 (8910): 1394–6. PMID 7910885. 
  • Tugores A, Magness ST, Brenner DA (1995). "A single promoter directs both housekeeping and erythroid preferential expression of the human ferrochelatase gene.". J. Biol. Chem. 269 (49): 30789–97. PMID 7983009. 
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. PMID 8125298. 
  • Dailey HA, Sellers VM, Dailey TA (1994). "Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases.". J. Biol. Chem. 269 (1): 390–5. PMID 8276824. 
  • Wang X, Poh-Fitzpatrick M, Carriero D, et al. (1993). "A novel mutation in erythropoietic protoporphyria: an aberrant ferrochelatase mRNA caused by exon skipping during RNA splicing.". Biochim. Biophys. Acta 1181 (2): 198–200. PMID 8481408. 
  • Nakahashi Y, Miyazaki H, Kadota Y, et al. (1993). "Molecular defect in human erythropoietic protoporphyria with fatal liver failure.". Hum. Genet. 91 (4): 303–6. PMID 8500787. 
  • Imoto S, Tanizawa Y, Sato Y, et al. (1996). "A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria.". Br. J. Haematol. 94 (1): 191–7. PMID 8757534. 
  • Crouse BR, Sellers VM, Finnegan MG, et al. (1997). "Site-directed mutagenesis and spectroscopic characterization of human ferrochelatase: identification of residues coordinating the [2Fe-2S] cluster.". Biochemistry 35 (50): 16222–9. doi:10.1021/bi9620114. PMID 8973195. 

[edit] External links

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Metabolism: amino acid metabolism - porphyrin enzymes
Porphyrin biosynthesis
Heme breakdown to bile