Protoporphyrinogen oxidase
Enzyme
| protoporphyrinogen oxidase | |
|---|---|
| Heme synthesis, note 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 | |
| BRENDA | enzyme data |
| ExPASy | NiceZyme view |
| KEGG | enzyme entry |
| MetaCyc | metabolic pathway |
| Rhea | reactions |
| PDB structures | RCSB PDB PDBe PDBsum |
| Gene Ontology | AmiGO / QuickGO |
Protoporphyrinogen oxidase or protox is an enzyme that in humans is encoded by the PPOX gene.
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.
01Gene
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.
02Function
This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX.
protoporphyrinogen IX 3 O2 3 H2O2 3 O2 3 H2O2 protoporphyrin IXThis protein is a flavoprotein associated with the outer surface of the inner mitochondrial membrane.
03Heme 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)
04Clinical 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.
05Inhibitors 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. 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.
Sources and credits
This article is adapted from the Wikipedia article “Protoporphyrinogen oxidase”, written by its contributors and licensed under CC BY-SA 4.0. Fathomly has changed the layout, removed citation markers, navigation and maintenance notices, and adjusted punctuation. This adapted version is shared under the same license. For references, see the original article.
Images, from Wikimedia Commons:
- 4ivm.jpg by Deposition authors: Xiaohong, Q., Baifan, W.; visualization author: User:Astrojan, CC BY-SA 4.0
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