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
herbicide
Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...
s.
Gene
The PPOX gene is located on the long (q) arm of
chromosome 1 at position 22, from
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
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.
Heme biosynthetic pathway
The following genes encode enzymes that catalyze the various steps in the heme
biosynthetic pathway:
* ''
ALAD'': aminolevulinate, delta-, dehydratase
* ''
ALAS1
Delta-aminolevulinate synthase 1 also known as ALAS1 is a protein that in humans is encoded by the ''ALAS1'' gene. ALAS1 is an aminolevulinic acid synthase.
Delta-aminolevulinate synthase catalyzes the condensation of glycine with succinyl-CoA t ...
'': 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 III decarboxylase (uroporphyrinogen decarboxylase, or UROD) is an enzyme () that in humans is encoded by the ''UROD'' gene.
Function
Uroporphyrinogen III decarboxylase is a homodimeric enzyme () that catalyzes the fifth step i ...
'': uroporphyrinogen decarboxylase
* ''
UROS'': uroporphyrinogen III synthase (congenital erythropoietic porphyria)
Clinical significance
Variegate porphyria
Variegate porphyria, also known by several other names, is an autosomal dominant porphyria that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the skin. The disorder results from low levels of the en ...
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
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
at position 59 (also written as Arg59Trp or R59W), is found in about 95 percent of
South African __NOTOC__
South African may relate to:
* The nation of South Africa
* South African Airways
* South African English
* South African people
* Languages of South Africa
* Southern Africa
Southern Africa is the southernmost subregion of the Afric ...
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
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
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
Acifluorfen is the ISO common name for an organic compound used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase which is necessary for chlorophyll synthesis. Soybeans naturally have a high tolerance to acifluorfen ...
and
fomesafen and the
pyrimidinedione
Pyrimidinediones are a class of chemical compounds characterized by a pyrimidine ring substituted with two carbonyl groups.
Examples include naturally occurring metabolites:
drugs:
* Fluorouracil
* Idoxuridine
* Primidone
* Trifluridine
Trif ...
s
butafenacil
Butafenacil is the International Organization for Standardization, ISO trivial name, common name for an organic compound of the pyrimidinedione chemical class used as an herbicide. It acts by enzyme inhibitor, inhibiting the enzyme protoporphyrino ...
and
saflufenacil
Saflufenacil is the ISO common name for an organic compound of the pyrimidinedione chemical class used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase to control broadleaf weeds in crops including soybeans and corn.
...
. The visible symptoms of treatment are
chlorosis and
desiccation
Desiccation () is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container.
...
. The damage is caused by an accumulation of protoporphyrin IX in the plant cells by inhibiting protox within the
tetrapyrrole biosynthesis pathway
Tetrapyrroles are a class of chemical compounds that contain four pyrrole or pyrrole-like rings. The pyrrole/pyrrole derivatives are linked by (methine, =- or methylene bridge, -- units), in either a linear or a cyclic fashion. Pyrroles are a fiv ...
. This is a potent
photosensitizer which activates oxygen, leading to
lipid peroxidation
Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which radical (chemistry), free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by ...
. Both light and oxygen are required for this process to kill the plant.
See also
*
Porphyrin
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
PDBe-KBprovides an overview of all the structure information available in the PDB for Human Protoporphyrinogen oxidase
{{Portal bar, Biology, border=no
EC 1.3.3