Uroporphyrinogen III decarboxylase

Uroporphyrinogen decarboxylase, also known as UROD, is a human gene.cite web | title = Entrez Gene: UROD uroporphyrinogen decarboxylase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7389| accessdate = ]

Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme (EC number|4.1.1.37, PDB|1URO) which 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.

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.

Silva & Ramos (2005) performed a detailed study of competing reaction mechanisms proposed for uroporphyrinogen decarboxylase. [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.]

PBB_Summary
section_title =
summary_text = 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. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.cite web | title = Entrez Gene: UROD uroporphyrinogen decarboxylase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7389| accessdate = ]

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Elder GH, Lee GB, Tovey JA |title=Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda. |journal=N. Engl. J. Med. |volume=299 |issue= 6 |pages= 274–8 |year= 1978 |pmid= 661926 |doi=
*cite journal | author=de Verneuil H, Bourgeois F, de Rooij F, "et al." |title=Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria. |journal=Hum. Genet. |volume=89 |issue= 5 |pages= 548–52 |year= 1992 |pmid= 1634232 |doi=
*cite journal | author=Romana M, Grandchamp B, Dubart A, "et al." |title=Identification of a new mutation responsible for hepatoerythropoietic porphyria. |journal=Eur. J. Clin. Invest. |volume=21 |issue= 2 |pages= 225–9 |year= 1991 |pmid= 1905636 |doi=
*cite journal | author=Garey JR, Harrison LM, Franklin KF, "et al." |title=Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda. |journal=J. Clin. Invest. |volume=86 |issue= 5 |pages= 1416–22 |year= 1990 |pmid= 2243121 |doi=
*cite journal | author=Garey JR, Hansen JL, Harrison LM, "et al." |title=A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda. |journal=Blood |volume=73 |issue= 4 |pages= 892–5 |year= 1989 |pmid= 2920211 |doi=
*cite journal | author=Roméo PH, Raich N, Dubart A, "et al." |title=Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA. |journal=J. Biol. Chem. |volume=261 |issue= 21 |pages= 9825–31 |year= 1986 |pmid= 3015909 |doi=
*cite journal | author=Dubart A, Mattei MG, Raich N, "et al." |title=Assignment of human uroporphyrinogen decarboxylase (URO-D) to the p34 band of chromosome 1. |journal=Hum. Genet. |volume=73 |issue= 3 |pages= 277–9 |year= 1986 |pmid= 3460962 |doi=
*cite journal | author=Romana M, Dubart A, Beaupain D, "et al." |title=Structure of the gene for human uroporphyrinogen decarboxylase. |journal=Nucleic Acids Res. |volume=15 |issue= 18 |pages= 7343–56 |year= 1987 |pmid= 3658695 |doi=
*cite journal | author=de Verneuil H, Grandchamp B, Beaumont C, "et al." |title=Uroporphyrinogen decarboxylase structural mutant (Gly281----Glu) in a case of porphyria. |journal=Science |volume=234 |issue= 4777 |pages= 732–4 |year= 1986 |pmid= 3775362 |doi=
*cite journal | author=Roberts AG, Elder GH, De Salamanca RE, "et al." |title=A mutation (G281E) of the human uroporphyrinogen decarboxylase gene causes both hepatoerythropoietic porphyria and overt familial porphyria cutanea tarda: biochemical and genetic studies on Spanish patients. |journal=J. Invest. Dermatol. |volume=104 |issue= 4 |pages= 500–2 |year= 1995 |pmid= 7706766 |doi=
*cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=
*cite journal | author=Meguro K, Fujita H, Ishida N, "et al." |title=Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria. |journal=J. Invest. Dermatol. |volume=102 |issue= 5 |pages= 681–5 |year= 1994 |pmid= 8176248 |doi=
*cite journal | author=Moran-Jimenez MJ, Ged C, Romana M, "et al." |title=Uroporphyrinogen decarboxylase: complete human gene sequence and molecular study of three families with hepatoerythropoietic porphyria. |journal=Am. J. Hum. Genet. |volume=58 |issue= 4 |pages= 712–21 |year= 1996 |pmid= 8644733 |doi=
*cite journal | author=McManus JF, Begley CG, Sassa S, Ratnaike S |title=Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria. |journal=Blood |volume=88 |issue= 9 |pages= 3589–600 |year= 1996 |pmid= 8896428 |doi=
*cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, "et al." |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=
*cite journal | author=Whitby FG, Phillips JD, Kushner JP, Hill CP |title=Crystal structure of human uroporphyrinogen decarboxylase. |journal=EMBO J. |volume=17 |issue= 9 |pages= 2463–71 |year= 1998 |pmid= 9564029 |doi= 10.1093/emboj/17.9.2463
*cite journal | author=Mendez M, Sorkin L, Rossetti MV, "et al." |title=Familial porphyria cutanea tarda: characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles. |journal=Am. J. Hum. Genet. |volume=63 |issue= 5 |pages= 1363–75 |year= 1998 |pmid= 9792863 |doi=
*cite journal | author=Wang H, Long Q, Marty SD, "et al." |title=A zebrafish model for hepatoerythropoietic porphyria. |journal=Nat. Genet. |volume=20 |issue= 3 |pages= 239–43 |year= 1998 |pmid= 9806541 |doi= 10.1038/3041
*cite journal | author=McManus JF, Begley CG, Sassa S, Ratnaike S |title=Three new mutations in the uroporphyrinogen decarboxylase gene in familial porphyria cutanea tarda. Mutation in brief no. 237. Online. |journal=Hum. Mutat. |volume=13 |issue= 5 |pages= 412 |year= 1999 |pmid= 10338097 |doi= 10.1002/(SICI)1098-1004(1999)13:5<412::AID-HUMU13>3.0.CO;2-N |doilabel=10.1002/(SICI)1098-1004(1999)13:5412::AID-HUMU133.0.CO;2-N
*cite journal | author=Christiansen L, Ged C, Hombrados I, "et al." |title=Screening for mutations in the uroporphyrinogen decarboxylase gene using denaturing gradient gel electrophoresis. Identification and characterization of six novel mutations associated with familial PCT. |journal=Hum. Mutat. |volume=14 |issue= 3 |pages= 222–32 |year= 1999 |pmid= 10477430 |doi= 10.1002/(SICI)1098-1004(1999)14:3<222::AID-HUMU5>3.0.CO;2-V |doilabel=10.1002/(SICI)1098-1004(1999)14:3222::AID-HUMU53.0.CO;2-V

References

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