Uroporphyrinogen III decarboxylase

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Uroporphyrinogen decarboxylase
Protein UROD PDB 1jph.png
PDB rendering based on 1jph.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols UROD ; PCT; UPD
External IDs OMIM613521 MGI98916 HomoloGene320 ChEMBL: 1681619 GeneCards: UROD Gene
EC number 4.1.1.37
RNA expression pattern
PBB GE UROD 208970 s at tn.png
PBB GE UROD 208971 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7389 22275
Ensembl ENSG00000126088 ENSMUSG00000028684
UniProt P06132 P70697
RefSeq (mRNA) NM_000374 NM_009478
RefSeq (protein) NP_000365 NP_033504
Location (UCSC) Chr 1:
45.48 – 45.48 Mb
Chr 4:
116.99 – 116.99 Mb
PubMed search [1] [2]

Uroporphyrinogen decarboxylase, also known as UROD, is an enzyme that in humans is encoded by the UROD gene.[1]

Function[edit]

This gene encodes the fifth enzyme of the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains.[1]

Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme (EC 4.1.1.37, PDB 1URO) that catalyzes the fifth step in heme biosynthesis: the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III.

Clinical significance[edit]

Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoietic porphyria.[1]

Mechanism[edit]

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.

The reaction catalyzed by UroD

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.[2] 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, catalytic proficiency, is the largest for any enzyme known, 6 x 1024 M−1.[3]

Proposed reaction mechanism of uroporphyrinogen III decarboxyklase


References[edit]

  1. ^ a b c "Entrez Gene: UROD uroporphyrinogen decarboxylase". 
  2. ^ Silva PJ, Ramos MJ. Density-functional study of mechanisms for the cofactor-free decarboxylation performed by uroporphyrinogen III decarboxylase. J Phys Chem B 2005;109:18195-200. doi:10.1021/jp051792s.
  3. ^ Lewis CA, Wolfenden R (November 2008). "Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes". Proc. Natl. Acad. Sci. U.S.A. 105 (45): 17328–33. doi:10.1073/pnas.0809838105. PMC 2582308. PMID 18988736. 

Further reading[edit]


Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)