Protoporphyrinogen oxidase

Last updated
PPOX
4ivm.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PPOX , PPO, V290M, VP, protoporphyrinogen oxidase
External IDs OMIM: 600923; MGI: 104968; HomoloGene: 262; GeneCards: PPOX; OMA:PPOX - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_008911

RefSeq (protein)

NP_032937

Location (UCSC) Chr 1: 161.17 – 161.18 Mb Chr 1: 171.1 – 171.11 Mb
PubMed search [3] [4]
Wikidata
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protoporphyrinogen oxidase
Heme synthesis.png
Heme synthesisnote that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
Identifiers
EC no. 1.3.3.4
CAS no. 53986-32-6
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 / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins

Protoporphyrinogen oxidase or protox is an enzyme that in humans is encoded by the PPOX gene. [5] [6] [7]

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.

Gene

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.

Function

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. [7]

Heme biosynthetic pathway

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

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.

Inhibitors as herbicides

Inhibition of protoporphyrinogen oxidase is a mechanism of action for several commercial herbicides including the nitrophenyl ethers acifluorfen and fomesafen and the pyrimidinediones butafenacil and saflufenacil. The visible symptoms of treatment are chlorosis and desiccation. The damage is caused by an accumulation of protoporphyrin IX in the plant cells by inhibiting protox within the tetrapyrrole biosynthesis pathway. [8] This is a potent photosensitizer which activates oxygen, leading to lipid peroxidation. Both light and oxygen are required for this process to kill the plant. [9] [10] [11]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000143224 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000062729 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Taketani S, Inazawa J, Abe T, Furukawa T, Kohno H, Tokunaga R, et al. (October 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.
  6. Frank J, McGrath JA, Poh-Fitzpatrick MB, Hawk JL, Christiano AM (July 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. S2CID   40509390.
  7. 1 2 "Entrez Gene: PPOX protoporphyrinogen oxidase".
  8. Brzezowski P, Ksas B, Havaux M, Grimm B, Chazaux M, Peltier G, et al. (2019-05-03). "The function of PROTOPORPHYRINOGEN IX OXIDASE in chlorophyll biosynthesis requires oxidised plastoquinone in Chlamydomonas reinhardtii". Communications Biology. 2 (1): 159. doi:10.1038/s42003-019-0395-5. PMC   6499784 . PMID   31069268.
  9. Dayan FE, Reddy KN, Duke SO (1999). "Structure-Activity Relationships of Diphenyl Ethers and Other Oxygen-Bridged Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. pp. 141–161. doi:10.1007/978-3-642-58633-0_5. ISBN   978-3-642-63674-5.
  10. Nagano E (1999). "Herbicidal Efficacy of Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. pp. 293–302. doi:10.1007/978-3-642-58633-0_11. ISBN   978-3-642-63674-5.
  11. Dayan FE, Duke SO (2010). "Protoporphyrinogen Oxidase-Inhibiting Herbicides". Hayes' Handbook of Pesticide Toxicology. pp. 1733–1751. doi:10.1016/B978-0-12-374367-1.00081-1. ISBN   9780123743671.

Further reading