Ferrochelatase

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Ferrochelatase
Protein FECH PDB 1hrk.png
PDB rendering based on 1hrk.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols FECH ; EPP; FCE
External IDs OMIM612386 MGI95513 HomoloGene113 GeneCards: FECH Gene
EC number 4.99.1.1
RNA expression pattern
PBB GE FECH 203116 s at tn.png
PBB GE FECH 203115 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2235 14151
Ensembl ENSG00000066926 ENSMUSG00000024588
UniProt P22830 P22315
RefSeq (mRNA) NM_000140 NM_007998
RefSeq (protein) NP_000131 NP_032024
Location (UCSC) Chr 18:
55.22 – 55.25 Mb
Chr 18:
64.46 – 64.49 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 the reaction:

protoporphyrin + Fe++protoheme + 2 H+.

Function[edit]

Ferrochelatase
Identifiers
EC number 4.99.1.1
CAS number 9012-93-5
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

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. 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)

Structure[edit]

Ferrochelatase
Identifiers
Symbol Ferrochelatase
Pfam PF00762
InterPro IPR001015
PROSITE PDOC00462
SCOP 1ak1
SUPERFAMILY 1ak1
OPM superfamily 137
OPM protein 1hrk

A ferrochelatase enzyme consists of 497 amino acid residues with a m.w. of 55.4 kDa.[1]

Clinical significance[edit]

Defects in ferrochelatase are associated with erythropoietic protoporphyria.[1]

Interactions[edit]

Ferrochelatase has been shown to interact with ABCB7.[2]

See also[edit]

References[edit]

  1. ^ a b c "Entrez Gene: FECH ferrochelatase (protoporphyria)". 
  2. ^ Taketani S, Kakimoto K, Ueta H, Masaki R, Furukawa T (Apr 2003). "Involvement of ABC7 in the biosynthesis of heme in erythroid cells: interaction of ABC7 with ferrochelatase". Blood 101 (8): 3274–80. doi:10.1182/blood-2002-04-1212. PMID 12480705. 

Further reading[edit]

  • Cox TM (Jun 1997). "Erythropoietic protoporphyria". Journal of Inherited Metabolic Disease 20 (2): 258–69. doi:10.1023/A:1005317124985. PMID 9211198. 
  • Buller RE, Schrader WT, O'Maller BW (May 1976). "Steroids and the practical aspects of performing binding studies". Journal of Steroid Biochemistry 7 (5): 321–6. doi:10.1016/0022-4731(76)90090-X. PMID 180343. 
  • Bonkowsky HL, Bloomer JR, Ebert PS, Mahoney MJ (Nov 1975). "Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts". The Journal of Clinical Investigation 56 (5): 1139–48. doi:10.1172/JCI108189. PMC 301976. PMID 1184741.  Check date values in: |year= / |date= mismatch (help)
  • Brenner DA, Didier JM, Frasier F, Christensen SR, Evans GA, Dailey HA (Jun 1992). "A molecular defect in human protoporphyria". American Journal of Human Genetics 50 (6): 1203–10. PMC 1682545. PMID 1376018. 
  • Nakahashi Y, Fujita H, Taketani S, Ishida N, Kappas A, Sassa S (Jan 1992). "The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria". Proceedings of the National Academy of Sciences of the United States of America 89 (1): 281–5. doi:10.1073/pnas.89.1.281. PMC 48220. PMID 1729699. 
  • Lamoril J, Boulechfar S, de Verneuil H, Grandchamp B, Nordmann Y, Deybach JC (Dec 1991). "Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene". Biochemical and Biophysical Research Communications 181 (2): 594–9. doi:10.1016/0006-291X(91)91231-Z. PMID 1755842.  Check date values in: |year= / |date= mismatch (help)
  • Diep A, Li C, Klisak I, Mohandas T, Sparkes RS, Gaynor R et al. (Dec 1991). "Assignment of the gene for cyclic AMP-response element binding protein 2 (CREB2) to human chromosome 2q24.1-q32". Genomics 11 (4): 1161–3. doi:10.1016/0888-7543(91)90047-I. PMID 1838349.  Check date values in: |year= / |date= mismatch (help)
  • Nakahashi Y, Taketani S, Okuda M, Inoue K, Tokunaga R (Dec 1990). "Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase". Biochemical and Biophysical Research Communications 173 (2): 748–55. doi:10.1016/S0006-291X(05)80099-3. PMID 2260980.  Check date values in: |year= / |date= mismatch (help)
  • Rossi E, Attwood PV, Garcia-Webb P, Costin KA (May 1990). "Inhibition of human lymphocyte ferrochelatase activity by hemin". Biochimica Et Biophysica Acta 1038 (3): 375–81. doi:10.1016/0167-4838(90)90251-A. PMID 2340297. 
  • Polson RJ, Lim CK, Rolles K, Calne RY, Williams R (Sep 1988). "The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria". Transplantation 46 (3): 386–9. doi:10.1097/00007890-198809000-00010. PMID 3047929. 
  • Bonkovsky HL, Schned AR (Jan 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 (Aug 1995). "Effect of cellular location on the function of ferrochelatase". The Journal of Biological Chemistry 270 (31): 18198–200. doi:10.1074/jbc.270.31.18198. PMID 7629135. 
  • Sarkany RP, Alexander GJ, Cox TM (Jun 1994). "Recessive inheritance of erythropoietic protoporphyria with liver failure". Lancet 343 (8910): 1394–6. doi:10.1016/S0140-6736(94)92525-9. PMID 7910885. 
  • Tugores A, Magness ST, Brenner DA (Dec 1994). "A single promoter directs both housekeeping and erythroid preferential expression of the human ferrochelatase gene". The Journal of Biological Chemistry 269 (49): 30789–97. PMID 7983009.  Check date values in: |year= / |date= mismatch (help)
  • Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • Dailey HA, Sellers VM, Dailey TA (Jan 1994). "Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases". The Journal of Biological Chemistry 269 (1): 390–5. PMID 8276824. 
  • Wang X, Poh-Fitzpatrick M, Carriero D, Ostasiewicz L, Chen T, Taketani S et al. (Apr 1993). "A novel mutation in erythropoietic protoporphyria: an aberrant ferrochelatase mRNA caused by exon skipping during RNA splicing". Biochimica Et Biophysica Acta 1181 (2): 198–200. doi:10.1016/0925-4439(93)90112-e. PMID 8481408. 
  • Nakahashi Y, Miyazaki H, Kadota Y, Naitoh Y, Inoue K, Yamamoto M et al. (May 1993). "Molecular defect in human erythropoietic protoporphyria with fatal liver failure". Human Genetics 91 (4): 303–6. doi:10.1007/BF00217346. PMID 8500787. 
  • Imoto S, Tanizawa Y, Sato Y, Kaku K, Oka Y (Jul 1996). "A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria". British Journal of Haematology 94 (1): 191–7. doi:10.1046/j.1365-2141.1996.d01-1771.x. PMID 8757534. 
  • Crouse BR, Sellers VM, Finnegan MG, Dailey HA, Johnson MK (Dec 1996). "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.  Check date values in: |year= / |date= mismatch (help)

External links[edit]