Izvorni kôd stranice UROD

{{Infokutija gen}}
'''Uroporpfirinogen III [[dekarboksilaza]]''' ('''uroporfirinogen dekarboksilaza''' ili '''UROD''') jest [[enzim]] ([[EC broj|EC 4.1.1.37]]) koji je kod [[ljudi]] [[kodon|kodiran]] [[gen]]om '''UROD''' sa [[hromosom 1|hromosoma 1]].<ref name="entrez">{{cite web | title = Entrez Gene: UROD uroporphyrinogen decarboxylase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7389}}</ref>

==Aminokiselinska sekvenca==
Dužina [[polipeptid]]nog lanca je  367 [[aminokiselina]], a [[molekularna masa|molekulska težina]]  40.787 [[Dalton (jedinica)|Da]].<ref name="UniProt">{{cite web|url=http://www.uniprot.org/uniprot/P06132#sequences |title=UniProt, P06132 |language=eng. |access-date=1. 12. 2021}}</ref>
{{legenda aminokiselina}}
<table  style="font-family:monospace;">
<tr style="text-align:right;"><th>10</th><th></th><th>20</th><th></th><th>30</th><th></th><th>40</th><th></th><th>50</th></tr>
<tr style="background-color: #eee;"><td>MEANGLGPQG</td><td style="background-color: #f9f9f9;"></td><td>FPELKNDTFL</td><td style="background-color: #f9f9f9;"></td><td>RAAWGEETDY</td><td style="background-color: #f9f9f9;"></td><td>TPVWCMRQAG</td><td style="background-color: #f9f9f9;"></td><td>RYLPEFRETR</td></tr>
<tr style="background-color: #eee;"><td>AAQDFFSTCR</td><td style="background-color: #f9f9f9;"></td><td>SPEACCELTL</td><td style="background-color: #f9f9f9;"></td><td>QPLRRFPLDA</td><td style="background-color: #f9f9f9;"></td><td>AIIFSDILVV</td><td style="background-color: #f9f9f9;"></td><td>PQALGMEVTM</td></tr>
<tr style="background-color: #eee;"><td>VPGKGPSFPE</td><td style="background-color: #f9f9f9;"></td><td>PLREEQDLER</td><td style="background-color: #f9f9f9;"></td><td>LRDPEVVASE</td><td style="background-color: #f9f9f9;"></td><td>LGYVFQAITL</td><td style="background-color: #f9f9f9;"></td><td>TRQRLAGRVP</td></tr>
<tr style="background-color: #eee;"><td>LIGFAGAPWT</td><td style="background-color: #f9f9f9;"></td><td>LMTYMVEGGG</td><td style="background-color: #f9f9f9;"></td><td>SSTMAQAKRW</td><td style="background-color: #f9f9f9;"></td><td>LYQRPQASHQ</td><td style="background-color: #f9f9f9;"></td><td>LLRILTDALV</td></tr>
<tr style="background-color: #eee;"><td>PYLVGQVVAG</td><td style="background-color: #f9f9f9;"></td><td>AQALQLFESH</td><td style="background-color: #f9f9f9;"></td><td>AGHLGPQLFN</td><td style="background-color: #f9f9f9;"></td><td>KFALPYIRDV</td><td style="background-color: #f9f9f9;"></td><td>AKQVKARLRE</td></tr>
<tr style="background-color: #eee;"><td>AGLAPVPMII</td><td style="background-color: #f9f9f9;"></td><td>FAKDGHFALE</td><td style="background-color: #f9f9f9;"></td><td>ELAQAGYEVV</td><td style="background-color: #f9f9f9;"></td><td>GLDWTVAPKK</td><td style="background-color: #f9f9f9;"></td><td>ARECVGKTVT</td></tr>
<tr style="background-color: #eee;"><td>LQGNLDPCAL</td><td style="background-color: #f9f9f9;"></td><td>YASEEEIGQL</td><td style="background-color: #f9f9f9;"></td><td>VKQMLDDFGP</td><td style="background-color: #f9f9f9;"></td><td>HRYIANLGHG</td><td style="background-color: #f9f9f9;"></td><td>LYPDMDPEHV</td></tr>
<tr style="background-color: #eee;"><td>GAFVDAVHKH</td><td style="background-color: #f9f9f9;"></td><td>SRLLRQN</td></tr>
</table>

== Funkcija ==

Uroporfirinogen III dekarboksilaza je homodimerni enzim ({{PDB|1URO}}) koji katalizuje peti korak u [[heme]] biosintezi, što odgovara eliminaciji [[karboksil]] grupa sa četiri [[acetatne]] strane lanci [[uroporfirinogen III]] daju [[koproporfirinogen III]]:
:[[uroporfirinogen III]] <math>\rightleftharpoons</math> [[koproporfirinogen III]] + 4 CO<sub>2</sub>

== Mehanizam ==

Pri niskim koncentracijama [[supstrat (biohemija)|supstrata]], vjeruje se da reakcija slijedi uređeni put, sa sekvencnim uklanjanjem [[ugljik-dioksid|CO<sub>2</sub>]] iz D, A, B i C prstenova, dok se pri višim razinama supstrata/enzima izgleda da je operativna nasumična ruta. Enzim u [[rastvor]]u funkcionira kao [[proteinski dimer|dimer]], a i enzimi  čovjeka i [[duhan]]a su [[kristalizacija|kristalizirani]] i riješeni u dobrim rezolucijama.

[[Slika:Uroporphyrinogen-decarboxylase.svg|thumb|left|400px|Reakcija koju je katalizirao UROD]]
UROD se smatra neobičnom dekarboksilazom, jer vrši dekarboksilaciju bez intervencije bilo kakvih kofaktora, za razliku od velike većine dekarboksilaza. Nedavno je predloženo da se njegov mehanizam odvija kroz protonaciju supstrata pomoću [[arginin]]skih  ostatka.

== Klinički značaj ==

Poznato je da mutacije i nedostatak ovog enzima uzrokuju porodičnu ''[[porphyria cutanea tarda]]'' i [[hepatoeritropoetska porfirija|hepatoeritropoetsku porfiriju]].<ref name="entrez"/>

Izvještaj iz 2008. pokazao je da je nekatalizirana brzina UroD-ove reakcije 10<sup>−19</sup> s<sup>−1</sup>, tako da je pri pH 10 ubrzanje  UroD u odnosu na nekataliziranu brzinu, tj. stručnost, veća  negop za bilo koji poznati enzim, 6 x 10<sup>24</sup> M<sup>−1</sup>.<ref name="pmid18988736">{{cite journal |vauthors=Lewis CA, Wolfenden R | title = Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 45 | pages = 17328–33 |date=novembar 2008 | pmid = 18988736 | doi = 10.1073/pnas.0809838105 | pmc = 2582308  | bibcode = 2008PNAS..10517328L | doi-access = free }}</ref>

[[slika:UroD mechanism.svg|thumb|670x670px|Predloženi mehanizam reakcije uroporfirinogen III dekarboksilaze|center]]
[[slika:Heme synthesis.png|left|framed| Sinteza hema: &mdash; neke reakcije dešavaju u [[citoplazma|citoplazmi]], a neke u [[mitohondrija]]ma (žuto)]]

==Reference==
{{reflist}}

==Dopunska literatura==
{{refbegin|33em}}
*{{cite journal  |vauthors=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=10.1056/NEJM197808102990603  }}
*{{cite journal   |vauthors=de Verneuil H, Bourgeois F, de Rooij F, etal |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=  10.1007/bf00219182|url=http://repub.eur.nl/pub/58484 |hdl=1765/58484 |s2cid=31811381 |hdl-access=free }}
*{{cite journal   |vauthors=Romana M, Grandchamp B, Dubart A, etal |title=Identification of a new mutation responsible for hepatoerythropoietic porphyria. |url=https://archive.org/details/sim_european-journal-of-clinical-investigation_1991-04_21_2/page/225 |journal=Eur. J. Clin. Invest. |volume=21 |issue= 2 |pages= 225–9 |year= 1991 |pmid= 1905636 |doi=10.1111/j.1365-2362.1991.tb01814.x  |s2cid=22358220 }}
*{{cite journal   |vauthors=Garey JR, Harrison LM, Franklin KF, etal |title=Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda. |url=https://archive.org/details/sim_journal-of-clinical-investigation_1990-11_86_5/page/1416 |journal=J. Clin. Invest. |volume=86 |issue= 5 |pages= 1416–22 |year= 1990 |pmid= 2243121 |doi=10.1172/JCI114856  | pmc=296884  }}
*{{cite journal   |vauthors=Garey JR, Hansen JL, Harrison LM, etal |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 |doi=10.1182/blood.V73.4.892.892 |pmid= 2920211 |doi-access=free }}
*{{cite journal   |vauthors=Roméo PH, Raich N, Dubart A, etal |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 |doi=10.1016/S0021-9258(18)67589-1 |pmid= 3015909 |doi-access=free }}
*{{cite journal   |vauthors=Dubart A, Mattei MG, Raich N, etal |title=Assignment of human uroporphyrinogen decarboxylase (URO-D) to the p34 band of chromosome 1. |url=https://archive.org/details/sim_human-genetics_1986-07_73_3/page/277 |journal=Hum. Genet. |volume=73 |issue= 3 |pages= 277–9 |year= 1986 |pmid= 3460962 |doi=10.1007/BF00401245  |s2cid=34478515 }}
*{{cite journal   |vauthors=Romana M, Dubart A, Beaupain D, etal |title=Structure of the gene for human uroporphyrinogen decarboxylase. |url=https://archive.org/details/sim_nucleic-acids-research_1987-09-25_15_18/page/n145 |journal=Nucleic Acids Res. |volume=15 |issue= 18 |pages= 7343–56 |year= 1987 |pmid= 3658695 |doi=10.1093/nar/15.18.7343  | pmc=306252  }}
*{{cite journal   |vauthors=de Verneuil H, Grandchamp B, Beaumont C, etal |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=10.1126/science.3775362  |bibcode=1986Sci...234..732D }}
*{{cite journal   |vauthors=Roberts AG, Elder GH, De Salamanca RE, etal |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. |url=https://archive.org/details/sim_journal-of-investigative-dermatology_1995-04_104_4/page/500 |journal=J. Invest. Dermatol. |volume=104 |issue= 4 |pages= 500–2 |year= 1995 |pmid= 7706766 |doi=10.1111/1523-1747.ep12605953  |doi-access=free }}
*{{cite journal  |vauthors=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=10.1016/0378-1119(94)90802-8  }}
*{{cite journal   |vauthors=Meguro K, Fujita H, Ishida N, etal |title=Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria |url=https://archive.org/details/sim_journal-of-investigative-dermatology_1994-05_102_5/page/681 |journal=J. Invest. Dermatol. |volume=102 |issue= 5 |pages= 681–5 |year= 1994 |pmid= 8176248 |doi=10.1111/1523-1747.ep12374134  }}
*{{cite journal   |vauthors=Moran-Jimenez MJ, Ged C, Romana M, etal |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 | pmc=1914669  }}
*{{cite journal  |vauthors=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 |doi=10.1182/blood.V88.9.3589.bloodjournal8893589 |pmid= 8896428 |doi-access=free }}
*{{cite journal   |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |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=10.1016/S0378-1119(97)00411-3  }}
*{{cite journal  |vauthors=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  | pmc=1170588 }}
*{{cite journal   |vauthors=Mendez M, Sorkin L, Rossetti MV, etal |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=10.1086/302119  | pmc=1377546  }}
*{{cite journal   |vauthors=Wang H, Long Q, Marty SD, etal |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 |s2cid=28379777 }}
*{{cite journal  |vauthors=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= 412–413 |year= 1999 |pmid= 10338097 |doi= 10.1002/(SICI)1098-1004(1999)13:5<412::AID-HUMU13>3.0.CO;2-N |doi-access= free }}
*{{cite journal   |vauthors=Christiansen L, Ged C, Hombrados I, etal |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 }}
{{refend}}
{{Clear}}

== Vanjski linkovi ==
* {{PDBe-KB2|P06132|Uroporphyrinogen decarboxylase}}
{{PDB Gallery|geneid=7389}}
{{Enzimi}}
{{Enzimi biosinteze porfirina}}
{{Lijaze ugljik-ugljik}}

{{Portal|Biologija|border=no}}

[[Kategorija:Geni na hromosomu 1]]
[[Kategorija:Enzimi]]
[[Kategorija:Ljudski proteini]]
[[Kategorija:Proteomika]]
[[Kategorija:EC 4.1.1]]