Uroporphyrinogen III decarboxylase

UROD
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1JPH, 1JPI, 1JPK, 1R3Q, 1R3R, 1R3S, 1R3T, 1R3V, 1R3W, 1R3Y, 1URO, 2Q6Z, 2Q71, 3GVQ, 3GVR, 3GVV, 3GVW, 3GW0, 3GW3
Identifiers
Aliases	UROD, PCT, UPD, uroporphyrinogen decarboxylase
External IDs	OMIM: 613521; MGI: 98916; HomoloGene: 320; GeneCards: UROD; OMA:UROD - orthologs
Gene location (Human)
Chr.	Chromosome 1 (human)
End	45,015,575 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	116,851,610 bp
RNA expression pattern
	Top expressed in
	trabecular bone; ; parotid gland; ; right adrenal gland; ; right adrenal cortex; ; parietal pleura; ; left adrenal cortex; ; endothelial cell; ; middle temporal gyrus; ; Brodmann area 23; ; bone marrow;
	Top expressed in
	fetal liver hematopoietic progenitor cell; ; internal carotid artery; ; endocardial cushion; ; human fetus; ; external carotid artery; ; facial motor nucleus; ; atrioventricular valve; ; Epithelium of choroid plexus; ; medullary collecting duct; ; renal corpuscle;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	protein binding; lyase activity; uroporphyrinogen decarboxylase activity; carboxy-lyase activity;
Cellular component	nucleoplasm; cytoplasm; cytosol;
Biological process	protoporphyrinogen IX biosynthetic process; porphyrin-containing compound biosynthetic process; heme biosynthetic process; heme metabolic process;
	Sources:Amigo / QuickGO
Orthologs
	7389
	22275
	ENSG00000126088
	ENSMUSG00000028684
	P06132
	P70697
	NM_000374
	NM_009478
	NP_000365
	NP_033504
	Wikidata
View/Edit Human	View/Edit Mouse

Uroporphyrinogen III decarboxylase (uroporphyrinogen decarboxylase, or UROD) is an enzyme (EC 4.1.1.37) that in humans is encoded by the UROD gene.^[5]

Function

Uroporphyrinogen III decarboxylase is a homodimeric enzyme (PDB: 1URO) that catalyzes the fifth step in heme biosynthesis, which corresponds to the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III:

uroporphyrinogen III

\rightleftharpoons

coproporphyrinogen III + 4 CO₂

Clinical significance

Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoietic porphyria.^[5] At least 65 disease-causing mutations in this gene have been discovered.^[6]

Mechanism

At low substrate concentrations, the reaction is believed to follow an ordered route, with the sequential removal of CO₂ from the D, A, B, and C rings, whereas at higher substrate/enzyme levels a random route seems to be operative. The enzyme functions as a dimer in solution, and both the enzymes from human and tobacco have been crystallized and solved at good resolutions.

UroD is regarded as an unusual decarboxylase, since it performs decarboxylations without the intervention of any cofactors, unlike the vast majority of decarboxylases. Its mechanism has recently been proposed to proceed through substrate protonation by an arginine residue.^[7] A 2008 report demonstrated that the uncatalyzed rate for UroD's reaction is 10⁻¹⁹ s⁻¹, so at pH 10 the rate acceleration of UroD relative to the uncatalyzed rate, i.e. catalytic proficiency, is the largest for any enzyme known, 6 x 10²⁴ M⁻¹.^[8]