Jump to content

Uroporphyrinogen III decarboxylase

From Wikipedia, the free encyclopedia

This is the current revision of this page, as edited by Thatsme314 (talk | contribs) at 00:45, 23 November 2023 (Importing Wikidata short description: "Mammalian protein found in Homo sapiens"). The present address (URL) is a permanent link to this version.

(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff)
UROD
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesUROD, PCT, UPD, uroporphyrinogen decarboxylase
External IDsOMIM: 613521; MGI: 98916; HomoloGene: 320; GeneCards: UROD; OMA:UROD - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000374

NM_009478

RefSeq (protein)

NP_000365

NP_033504

Location (UCSC)Chr 1: 45.01 – 45.02 MbChr 4: 116.85 – 116.85 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

[edit]

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 coproporphyrinogen III + 4 CO2

Clinical significance

[edit]

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

[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.[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]

Proposed reaction mechanism of uroporphyrinogen III decarboxylase

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000126088Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028684Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: UROD uroporphyrinogen decarboxylase".
  6. ^ Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.
  7. ^ Silva PJ, Ramos MJ (2005). "Density-functional study of mechanisms for the cofactor-free decarboxylation performed by uroporphyrinogen III decarboxylase". J Phys Chem B. 109 (38): 18195–200. doi:10.1021/jp051792s. PMID 16853337.
  8. ^ 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. Bibcode:2008PNAS..10517328L. doi:10.1073/pnas.0809838105. PMC 2582308. PMID 18988736.

Further reading

[edit]
[edit]
  • Overview of all the structural information available in the PDB for UniProt: P06132 (Uroporphyrinogen decarboxylase) at the PDBe-KB.
Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)