{{Short description|Class of enzymes}} {{infobox enzyme | Name = Uroporphyrinogen-III synthase | EC_number = 4.2.1.75 | CAS_number = 37340-55-9 | GO_code = 0004852 | image = 3d8n.jpg | width = 270 | caption = Uroporphyrinogen-III synthase monomer, Thermus thermophilus }} {{infobox protein | Name = Uroporphyrinogen III synthase | caption = | image = | width = | HGNCid = 12592 | Symbol = UROS | AltSymbols = | EntrezGene = 7390 | OMIM = 606938 | RefSeq = NM_000375 | UniProt = P10746 | PDB = | ECnumber = 4.2.1.75 | Chromosome = 10 | Arm = q | Band = 25.2-26.3 | LocusSupplementaryData = }} {{Infobox protein family | Symbol = HEM4 | Name = Uroporphyrinogen-III synthase HemD | image = PDB 1wd7 EBI.jpg | width = | caption = crystal structure of uroporphyrinogen iii synthase from an extremely thermophilic bacterium thermus thermophilus hb8 (wild type, native, form-2 crystal) | Pfam = PF02602 | Pfam_clan = | InterPro = IPR003754 | SMART = | PROSITE = | MEROPS = | SCOP = 1jr2 | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Uroporphyrinogen III synthase''' ({{EnzExplorer|4.2.1.75}}) is an enzyme involved in the metabolism of the cyclic tetrapyrrole compound porphyrin. It is involved in the conversion of hydroxymethylbilane into uroporphyrinogen III. This enzyme catalyses the inversion of the final pyrrole unit (ring D) of the linear tetrapyrrole molecule, linking it to the first pyrrole unit (ring A), thereby generating a large macrocyclic structure, uroporphyrinogen III.<ref name="pmid11215515">{{cite journal |vauthors=Raux E, Schubert HL, Warren MJ | title = Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum | journal = Cell. Mol. Life Sci. | volume = 57 | issue = 13–14 | pages = 1880–93 |date=December 2000 | pmid = 11215515 | doi = 10.1007/PL00000670| s2cid = 583311 | pmc = 11147154 }}</ref> The enzyme folds into two alpha/beta domains connected by a beta-ladder, the active site being located between the two domains.<ref name="pmid11689424">{{cite journal |vauthors=Mathews MA, Schubert HL, Whitby FG, Alexander KJ, Schadick K, Bergonia HA, Phillips JD, Hill CP | title = Crystal structure of human uroporphyrinogen III synthase | journal = EMBO J. | volume = 20 | issue = 21 | pages = 5832–9 |date=November 2001 | pmid = 11689424 | pmc = 125291 | doi = 10.1093/emboj/20.21.5832 }}</ref>

[[Image:Heme synthesis.png|center|framed|Heme synthesis&mdash;note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)]]

==Function== The enzyme catalyses the cyclisation reaction of hydroxymethylbilane into uroporphyrinogen III via a spiro intermediate which allows one of the pyrrole rings to convert its initial acetate to propionate configuration into a propionate-acetate one.<ref>{{cite journal |title=Biosynthesis of the pigments of life: formation of the macrocycle |last1=Battersby |first1= Alan R. |last2=Fookes |first2=Christopher J. R. |last3=Matcham |first3=George W.J. |last4=McDonald |first4=Edward |journal =Nature |year =1980 |volume=285 |issue=5759 |pages =17–21 |doi=10.1038/285017a0 |pmid=6769048 |bibcode=1980Natur.285...17B |s2cid=9070849 }}</ref><ref>{{KEGG enzyme|4.2.1.75}}</ref>

{{chemrxn|width=55%| {{chemrxn/cpd|hydroxymethylbilane }} {{chemrxn/arw|direction=forward|fwd_out={{chem2|H2O}}|rev_in={{chem2|H2O}} }} {{chemrxn/cpd|uroporphyrinogen III }} }}

==Pathology== A deficiency is associated with Gunther's disease, also known as congenital erythropoietic porphyria (CEP). This is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase.<ref name="pmid17270473">{{cite journal |vauthors=To-Figueras J, Badenas C, Mascaro JM, Madrigal I, Merino A, Bastida P, Lecha M, Herrero C | title = Study of the genotype-phenotype relationship in four cases of congenital erythropoietic porphyria | journal = Blood Cells Mol. Dis. | volume = 38 | issue = 3 | pages = 242–6 | year = 2007 | pmid = 17270473 | doi = 10.1016/j.bcmd.2006.12.001 }}</ref>

==References== {{reflist}}

==External links== * {{MeshName|Uroporphyrinogen+III+synthase}}

{{InterPro content|IPR003754}} {{Porphyrin biosynthesis enzymes}} {{Carbon-oxygen lyases}} {{Enzymes}} {{Portal bar|Biology|border=no}}

Category:EC 4.2.1

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