Protoporphyrinogen oxidase

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External IDsGeneCards: [1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)n/an/a
PubMed searchn/an/a
View/Edit Human
protoporphyrinogen oxidase
Heme synthesis.png
Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
EC number1.3.3.4
CAS number53986-32-6
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

Protoporphyrinogen oxidase is an enzyme that in humans is encoded by the PPOX gene.[1][2][3]

Protoporphyrinogen oxidase is responsible for the seventh step in biosynthesis of protoporphyrin IX. This porphyrin is the precursor to hemoglobin, the oxygen carrier in animals, and chlorophyll, the dye in plants. The enzyme catalyzes the dehydrogenation (removal of hydrogen atoms) of protoporphyrinogen IX (the product of the sixth step in the production of heme) to form protoporphyrin IX. One additional enzyme must modify protoporphyrin IX before it becomes heme. Inhibition of this enzyme is a strategy used in certain herbicides.


The PPOX gene is located on the long (q) arm of chromosome 1 at position 22, from base pair 157,949,266 to base pair 157,954,082.


This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX. This protein is a flavoprotein associated with the outer surface of the inner mitochondrial membrane.[3]

Heme biosynthetic pathway

The following genes encode enzymes that catalyze the various steps in the heme biosynthetic pathway:

  • ALAD: aminolevulinate, delta-, dehydratase
  • ALAS1: aminolevulinate, delta-, synthase 1
  • ALAS2: aminolevulinate, delta-, synthase 2 (sideroblastic/hypochromic anemia)
  • CPOX: coproporphyrinogen oxidase
  • FECH: ferrochelatase (protoporphyria)
  • HMBS: hydroxymethylbilane synthase
  • PPOX: protoporphyrinogen oxidase
  • UROD: uroporphyrinogen decarboxylase
  • UROS: uroporphyrinogen III synthase (congenital erythropoietic porphyria)

Clinical significance

Variegate porphyria is caused by mutations in the PPOX gene. More than 100 mutations that can cause variegate porphyria have been identified in the PPOX gene. One mutation, a substitution of the amino acid tryptophan for arginine at position 59 (also written as Arg59Trp or R59W), is found in about 95 percent of South African families with variegate porphyria. Mutations in the PPOX gene reduce the activity of the enzyme made by the gene, allowing byproducts of heme production to build up in the body. This buildup, in combination with nongenetic factors (such as certain drugs, alcohol and dieting), causes this type of porphyria.

See also


  1. Taketani S, Inazawa J, Abe T, Furukawa T, Kohno H, Tokunaga R, Nishimura K, Inokuchi H (Oct 1995). "The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1". Genomics. 29 (3): 698–703. doi:10.1006/geno.1995.9949. PMID 8575762.
  2. Frank J, McGrath JA, Poh-Fitzpatrick MB, Hawk JL, Christiano AM (Jul 1999). "Mutations in the translation initiation codon of the protoporphyrinogen oxidase gene underlie variegate porphyria". Clinical and Experimental Dermatology. 24 (4): 296–301. doi:10.1046/j.1365-2230.1999.00484.x. PMID 10457135.
  3. 3.0 3.1 "Entrez Gene: PPOX protoporphyrinogen oxidase".

Further reading

  • Elder GH (1998). "Genetic defects in the porphyrias: types and significance". Clinics in Dermatology. 16 (2): 225–33. doi:10.1016/S0738-081X(97)00202-2. PMID 9554235.
  • Maneli MH, Corrigall AV, Klump HH, Davids LM, Kirsch RE, Meissner PN (Aug 2003). "Kinetic and physical characterisation of recombinant wild-type and mutant human protoporphyrinogen oxidases". Biochimica et Biophysica Acta. 1650 (1–2): 10–21. doi:10.1016/s1570-9639(03)00186-9. PMID 12922165.
  • Morgan RR, Errington R, Elder GH (Jan 2004). "Identification of sequences required for the import of human protoporphyrinogen oxidase to mitochondria". The Biochemical Journal. 377 (Pt 2): 281–7. doi:10.1042/BJ20030978. PMC 1223874. PMID 14535846.
  • Sassa S, Kappas A (Feb 2000). "Molecular aspects of the inherited porphyrias". Journal of Internal Medicine. 247 (2): 169–78. doi:10.1046/j.1365-2796.2000.00618.x. PMID 10692079.
  • Nishimura K, Taketani S, Inokuchi H (Apr 1995). "Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli". The Journal of Biological Chemistry. 270 (14): 8076–80. doi:10.1074/jbc.270.14.8076. PMID 7713909.
  • Dailey TA, Meissner P, Dailey HA (Jan 1994). "Expression of a cloned protoporphyrinogen oxidase". The Journal of Biological Chemistry. 269 (2): 813–5. PMID 8288631.
  • Dailey TA, Dailey HA, Meissner P, Prasad AR (Dec 1995). "Cloning, sequence, and expression of mouse protoporphyrinogen oxidase". Archives of Biochemistry and Biophysics. 324 (2): 379–84. doi:10.1006/abbi.1995.0051. PMID 8554330.
  • Meissner PN, Dailey TA, Hift RJ, Ziman M, Corrigall AV, Roberts AG, Meissner DM, Kirsch RE, Dailey HA (May 1996). "A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria". Nature Genetics. 13 (1): 95–7. doi:10.1038/ng0596-95. PMID 8673113.
  • Dailey TA, Dailey HA (Jan 1996). "Human protoporphyrinogen oxidase: expression, purification, and characterization of the cloned enzyme". Protein Science. 5 (1): 98–105. doi:10.1002/pro.5560050112. PMC 2143237. PMID 8771201.
  • Puy H, Robréau AM, Rosipal R, Nordmann Y, Deybach JC (Sep 1996). "Protoporphyrinogen oxidase: complete genomic sequence and polymorphisms in the human gene". Biochemical and Biophysical Research Communications. 226 (1): 226–30. doi:10.1006/bbrc.1996.1337. PMID 8806618.
  • Deybach JC, Puy H, Robréau AM, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y (Mar 1996). "Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria". Human Molecular Genetics. 5 (3): 407–10. doi:10.1093/hmg/5.3.407. PMID 8852667.
  • Lam H, Dragan L, Tsou HC, Merk H, Peacocke M, Goerz G, Sassa S, Poh-Fitzpatrick M, Bickers DR, Christiano AM (Jan 1997). "Molecular basis of variegate porphyria: a de novo insertion mutation in the protoporphyrinogen oxidase gene". Human Genetics. 99 (1): 126–9. doi:10.1007/s004390050325. PMID 9003509.
  • Dailey HA, Dailey TA (Feb 1997). "Characteristics of human protoporphyrinogen oxidase in controls and variegate porphyrias". Cellular and Molecular Biology. 43 (1): 67–73. PMID 9074790.
  • Frank J, Poh-Fitzpatrick MB, King LE, Christiano AM (Aug 1998). "The genetic basis of "Scarsdale Gourmet Diet" variegate porphyria: a missense mutation in the protoporphyrinogen oxidase gene". Archives of Dermatological Research. 290 (8): 441–5. doi:10.1007/s004030050333. PMID 9763307.
  • Roberts AG, Puy H, Dailey TA, Morgan RR, Whatley SD, Dailey HA, Martasek P, Nordmann Y, Deybach JC, Elder GH (Nov 1998). "Molecular characterization of homozygous variegate porphyria". Human Molecular Genetics. 7 (12): 1921–5. doi:10.1093/hmg/7.12.1921. PMID 9811936.
  • Whatley SD, Puy H, Morgan RR, Robreau AM, Roberts AG, Nordmann Y, Elder GH, Deybach JC (Oct 1999). "Variegate porphyria in Western Europe: identification of PPOX gene mutations in 104 families, extent of allelic heterogeneity, and absence of correlation between phenotype and type of mutation". American Journal of Human Genetics. 65 (4): 984–94. doi:10.1086/302586. PMC 1288269. PMID 10486317.
  • Suzuki Y, Ishihara D, Sasaki M, Nakagawa H, Hata H, Tsunoda T, Watanabe M, Komatsu T, Ota T, Isogai T, Suyama A, Sugano S (Mar 2000). "Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries". Genomics. 64 (3): 286–97. doi:10.1006/geno.2000.6076. PMID 10756096.
  • Corrigall AV, Hift RJ, Davids LM, Hancock V, Meissner D, Kirsch RE, Meissner PN (Apr 2000). "Homozygous variegate porphyria in South Africa: genotypic analysis in two cases". Molecular Genetics and Metabolism. 69 (4): 323–30. doi:10.1006/mgme.2000.2975. PMID 10870850.
  • Kauppinen R, Timonen K, von und zu Fraunberg M, Laitinen E, Ahola H, Tenhunen R, Taketani S, Mustajoki P (Apr 2001). "Homozygous variegate porphyria: 20 y follow-up and characterization of molecular defect". The Journal of Investigative Dermatology. 116 (4): 610–3. doi:10.1046/j.1523-1747.2001.01293.x. PMID 11286631.
  • Palmer RA, Elder GH, Barrett DF, Keohane SG (Apr 2001). "Homozygous variegate porphyria: a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene". The British Journal of Dermatology. 144 (4): 866–9. doi:10.1046/j.1365-2133.2001.04147.x. PMID 11298551.
  • Corrigall AV, Hift RJ, Davids LM, Hancock V, Meissner D, Kirsch RE, Meissner PN (May 2001). "Identification of the first variegate porphyria mutation in an indigenous black South African and further evidence for heterogeneity in variegate porphyria". Molecular Genetics and Metabolism. 73 (1): 91–6. doi:10.1006/mgme.2001.3163. PMID 11350188.
  • Donnelly JG, Detombe S, Hindmarsh JT (2002). "Single-strand conformational polymorphism and denaturing gradient gel electrophoresis in screening for variegate porphyria: identification of two new mutations". Annals of Clinical and Laboratory Science. 32 (2): 107–13. PMID 12017191.