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MetaCyc Enzyme: protoporphyrinogen oxidase

Gene: PPOX Accession Number: HS07011 (MetaCyc)

Synonyms: PPO

Species: Homo sapiens

Subunit composition of protoporphyrinogen oxidase = [PPOX]2
         Protoporphyrinogen oxidase = PPOX

Protoporphyrinogen oxidase catalyzes an unusual six-electron oxidation of protoporphyrinogen IX to protoporphyrin IX, the penultimate reaction in superpathway of heme biosynthesis from glycine [Nishimura95a]. The reaction requires the presence of molecular oxygen and the enzyme is located on the cytosolic side of the inner mitochondrial membrane [Deybach85].

The human gene has been cloned from placenta and expressed in Escherichia coli [Dailey96]. The purified recombinant enzyme is a 100 kDa homodimer, utilizes 3 moles of molecular oxygen per mol of substrate, and may produce hydrogen peroxide [Dailey96a]. The enzyme contains one noncovalently bound FAD per dimer [Dailey96].

Protoporphyrinogen oxidase is expressed in a variety of tissues including heart, lung, kidney, brain and placenta. Deficiencies of the protein lead to variegate porphyria which causes accumulation and increased excretion of porphyrins or porphyrin precursors [Deybach96].

Gene Citations: [Taketani95]

Locations: mitochondrion, mitochondrial inner membrane

Map Position: [161,136,181 -> 161,141,010]

Molecular Weight of Polypeptide: 50.765 kD (from nucleotide sequence), 51.0 kD (experimental)

Molecular Weight of Multimer: 100.0 kD (experimental)

Unification Links: ArrayExpress:P50336 , Ensembl:ENSG00000143224 , Entrez-gene:5498 , Entrez-Nucleotide:BC002357 , Entrez-Nucleotide:D38537 , Entrez-Nucleotide:U26446 , Entrez:AAA67690 , Entrez:AAH02357 , Entrez:BAA07538 , GeneCards:PPOX , Mint:MINT-1402949 , MOPED:P50336 , OMIM:176200 , OMIM:600923 , PhosphoSite:P50336 , Pride:P50336 , Protein Model Portal:P50336 , RefSeq:NM_000309 , RefSeq:NP_000300 , SMR:P50336 , String:9606.ENSP00000343943 , UCSC Human Genome:NM_000309 , UniGene:100016 , UniProt:P50336

Relationship Links: InterPro:IN-FAMILY:IPR002937 , InterPro:IN-FAMILY:IPR004572 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR027418 , PDB:Structure:3NKS , PDB:Structure:4IVM , PDB:Structure:4IVO , Pfam:IN-FAMILY:PF01593

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0006783 - heme biosynthetic process
Molecular Function: GO:0004729 - oxygen-dependent protoporphyrinogen oxidase activity
Cellular Component: GO:0005739 - mitochondrion
GO:0005743 - mitochondrial inner membrane

Created 20-Mar-2008 by Caspi R , SRI International

Enzymatic reaction of: protoporphyrinogen oxidase

EC Number:

protoporphyrinogen IX + 3 oxygen <=> protoporphyrin IX + 3 hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of heme biosynthesis from glycine , heme biosynthesis I (aerobic)

Cofactors or Prosthetic Groups: FAD [Dailey96]

Inhibitors (Unknown Mechanism): acifluorfen [Dailey96]

Kinetic Parameters:

Km (μM)
protoporphyrinogen IX


Dailey96: Dailey TA, Dailey HA (1996). "Human protoporphyrinogen oxidase: expression, purification, and characterization of the cloned enzyme." Protein Sci 5(1);98-105. PMID: 8771201

Dailey96a: Dailey HA, Dailey TA (1996). "Protoporphyrinogen oxidase of Myxococcus xanthus. Expression, purification, and characterization of the cloned enzyme." J Biol Chem 271(15);8714-8. PMID: 8621504

Deybach85: Deybach JC, da Silva V, Grandchamp B, Nordmann Y (1985). "The mitochondrial location of protoporphyrinogen oxidase." Eur J Biochem 149(2);431-5. PMID: 3996415

Deybach96: Deybach JC, Puy H, Robreau AM, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y (1996). "Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria." Hum Mol Genet 5(3);407-10. PMID: 8852667

Nishimura95a: Nishimura K, Taketani S, Inokuchi H (1995). "Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli." J Biol Chem 270(14);8076-80. PMID: 7713909

Taketani95: Taketani S, Inazawa J, Abe T, Furukawa T, Kohno H, Tokunaga R, Nishimura K, Inokuchi H (1995). "The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1." Genomics 29(3);698-703. PMID: 8575762

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Thu Sep 3, 2015, BIOCYC14A.