Protoporphyrinogen oxidase

Protoporphyrinogen oxidase
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3NKS, 4IVM, 4IVO
Identifiers
Symbols	PPOX ; PPO; V290M; VP
External IDs	OMIM: 600923 MGI: 104968 HomoloGene: 262 GeneCards: PPOX Gene
EC number	1.3.3.4
Gene ontology Molecular function • oxygen-dependent protoporphyrinogen oxidase activity • flavin adenine dinucleotide binding Cellular component • mitochondrial intermembrane space • intrinsic component of mitochondrial inner membrane • integral component of mitochondrial inner membrane • mitochondrial membrane Biological process • porphyrin-containing compound metabolic process • porphyrin-containing compound biosynthetic process • protoporphyrinogen IX biosynthetic process • heme biosynthetic process • response to drug • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5498	19044
Ensembl	ENSG00000143224	ENSMUSG00000062729
UniProt	P50336	P51175
RefSeq (mRNA)	NM_000309	NM_008911
RefSeq (protein)	NP_000300	NP_032937
Location (UCSC)	Chr 1: 161.17 – 161.18 Mb	Chr 1: 171.28 – 171.28 Mb
PubMed search	[1]	[2]

protoporphyrinogen oxidase
Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
Identifiers
EC number	1.3.3.4
CAS number	Template:CAS
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 / EGO
Search PMC articles PubMed articles NCBI proteins

q <12i3u812228, )l+1299qq

Protoporphyrinogen oxidase 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.

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.

Heme 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)

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.

See also

• porphyrin