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Protoporphyrinogen oxidase or protox is an enzyme that in humans is encoded by the PPOXgene.
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.
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 acidtryptophan 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 pyrimidinedionesbutafenacil 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. 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.
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Dailey HA, Dailey TA (February 1997). "Characteristics of human protoporphyrinogen oxidase in controls and variegate porphyrias". Cellular and Molecular Biology. 43 (1): 67–73. PMID9074790.
Frank J, Poh-Fitzpatrick MB, King LE, Christiano AM (August 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. PMID9763307. S2CID32988570.
Suzuki Y, Ishihara D, Sasaki M, Nakagawa H, Hata H, Tsunoda T, et al. (March 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. PMID10756096.
Corrigall AV, Hift RJ, Davids LM, Hancock V, Meissner D, Kirsch RE, Meissner PN (April 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. PMID10870850.
Palmer RA, Elder GH, Barrett DF, Keohane SG (April 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. PMID11298551. S2CID41419729.
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. PMID11350188.
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. PMID12017191.
External links
PDBe-KB provides an overview of all the structure information available in the PDB for Human Protoporphyrinogen oxidase
Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)