Protoporphyrinogen oxidase or protox is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''PPOX''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Protoporphyrinogen oxidase is responsible for the seventh step in biosynthesis of

protoporphyrin IX Protoporphyrin IX is an organic compound, classified as a porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like heme (hemoglobin) and chlorophyll. It is a deeply colored solid that is not sol ...

. This porphyrin is the precursor to

hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...

, the

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

carrier in animals, and

chlorophyll Chlorophyll is any of several related green pigments found in cyanobacteria and in the chloroplasts of algae and plants. Its name is derived from the Greek words (, "pale green") and (, "leaf"). Chlorophyll allows plants to absorb energy ...

, the dye in plants. The enzyme catalyzes the

dehydrogenation In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...

(removal of

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

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 weed killers, 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 f ...

Gene

The PPOX gene is located on the long (q) arm of

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which a ...

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 Protoporphyrinogen IX is an organic compound, organic chemical compound which is produced along the synthesis of porphyrins, a class of critical biochemicals that include hemoglobin and chlorophyll. It is a direct precursor of protoporphyrin IX. ...

to form

. This protein is a

flavoprotein Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin. These proteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. ...

associated with the outer surface of the

inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...

Heme biosynthetic pathway

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

biosynthetic Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme- catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthesis) serve ...

pathway: * ''

ALAD Aminolevulinic acid dehydratase (porphobilinogen synthase, or ALA dehydratase, or aminolevulinate dehydratase) is an enzyme () that in humans is encoded by the ''ALAD'' gene. Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate dehydra ...

'': aminolevulinate, delta-, dehydratase * '' ALAS1'': aminolevulinate, delta-, synthase 1 * ''

ALAS2 Delta-aminolevulinate synthase 2 also known as ALAS2 is a protein that in humans is encoded by the ''ALAS2'' gene. ALAS2 is an aminolevulinic acid synthase. The product of this gene specifies an erythroid-specific mitochondrially located enzy ...

'': 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 ...

'': uroporphyrinogen decarboxylase * ''

UROS The Uru or Uros () are an indigenous people of Bolivia and Peru. They live on a still-growing group of about 120 self-fashioned floating islands in Lake Titicaca near Puno. They form three main groups: the Uru-Chipaya, Uru-Murato, and Uru ...

'': 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 enz ...

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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

for

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

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 Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

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

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 Primidone, sold ...

s butafenacil and saflufenacil. The visible symptoms of treatment are

chlorosis In botany, chlorosis is a condition in which leaves produce insufficient chlorophyll. As chlorophyll is responsible for the green color of leaves, chlorotic leaves are pale, yellow, or yellow-white. The affected plant has little or no ability to ...

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 ...

. 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 Photosensitizers are light absorbers that alter the course of a photochemical reaction. They usually are catalysts. They can function by many mechanisms; sometimes they abstract an electron from the substrate, and sometimes they abstract a hydro ...

which activates oxygen, leading to

lipid peroxidation Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz ...

. Both light and oxygen are required for this process to kill the plant.

References

External links

PDBe-KB
provides an overview of all the structure information available in the PDB for Human Protoporphyrinogen oxidase {{Portal bar, Biology, border=no EC 1.3.3