Chemistry:Uroporphyrinogen III
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| Names | |
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| IUPAC name
3-[7,12,18-Tris(2-carboxyethyl)-3,8,13,17-tetrakis(carboxymethyl)-5,10,15,20,21,22,23,24-octahydroporphyrin-2-yl]propanoic acid
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| Identifiers | |
3D model (JSmol)
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| 605190 | |
| ChEBI | |
| ChemSpider | |
| 1166130 | |
| KEGG | |
| MeSH | Uroporphyrinogen+III |
PubChem CID
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| Properties | |
| C40H44N4O16 | |
| Molar mass | 836.795 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
| Infobox references | |
Uroporphyrinogen III is a tetrapyrrole, the first macrocyclic intermediate in the biosynthesis of heme, chlorophyll, vitamin B12, and siroheme. It is a colorless compound, like other porphyrinogens.[1]
Structure
The molecular structure of uroporphyrinogen III can be described as a hexahydroporphine core, where each pyrrole ring has the hydrogen atoms on its two outermost carbons replaced by an acetic acid group (–CH
2–COOH, "A") and a propionic acid group (–CH
2–CH
2–COOH, "P"). The groups are attached in an asymmetric way: going around the macrocycle, the order is AP-AP-AP-PA.
Biosynthesis and metabolism
In the general porphyrin biosynthesis pathway, uroporphyrinogen III is derived from the linear tetrapyrrole hydroxymethylbilane by the action of the enzyme uroporphyrinogen-III synthase. This catalyses the cyclisation reaction via a spiro intermediate which allows one of the pyrrole rings to convert its initial acetate to propionate configuration into a propionate-acetate one.[2][3][4][5]
In the biosynthesis of hemes and chlorophylls, uroporphyrinogen III is converted into coproporphyrinogen III by the enzyme uroporphyrinogen III decarboxylase.[6]
In the biosynthesis of sirohemes, uroporphyrinogen III is converted by two methyl transferases to dihydrosirohydrochlorin, which is subsequently oxidized sirohydrochlorin, a precursor to the siroheme prosthetic group.
Medical significance
If uroporphyrinogen-III synthase is not present or inactive, the hydroxymethylbilane will spontaneously cyclise into the structural isomer uroporphyrinogen I, which differs from the III isomer in that the acetic acid ("A") and propionic acid ("P") groups are arranged in a rotationally symmetric order, AP-AP-AP-AP. In this case, the next step produced coproporphyrinogen I, which accumulates — leading to the pathological condition congenital erythropoietic porphyria[5]
See also
References
- ↑ Dalton, J (1969). "Formation of the Macrocyclic Ring in Tetrapyrrole Biosynthesis". Nature 223 (5211): 1151–1153. doi:10.1038/2231151a0. PMID 5810686. Bibcode: 1969Natur.223.1151D.
- ↑ Battersby, Alan R.; Fookes, Christopher J. R.; Matcham, George W.J.; McDonald, Edward (1980). "Biosynthesis of the pigments of life: formation of the macrocycle". Nature 285 (5759): 17–21. doi:10.1038/285017a0. PMID 6769048. Bibcode: 1980Natur.285...17B.
- ↑ Enzyme 4.2.1.75 at KEGG Pathway Database.
- ↑ Paul R. Ortiz de Montellano (2008). Wiley Encyclopedia of Chemical Biology. John Wiley & Sons. pp. 1–10. doi:10.1002/9780470048672.wecb221. ISBN 978-0-470-04867-2.
- ↑ 5.0 5.1 S. Sassa and A. Kappas (2000): "Molecular aspects of the inherited porphyrias". Journal of Internal Medicine, volume 247, issue 2, pages 169-178. doi:10.1046/j.1365-2796.2000.00618.x
- ↑ "Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes". Proc. Natl. Acad. Sci. U.S.A. 105 (45): 17328–33. November 2008. doi:10.1073/pnas.0809838105. PMID 18988736. Bibcode: 2008PNAS..10517328L.
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