Uroporphyrinogen III

Uroporphyrinogen III

Names
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
Identifiers
CAS Number	1976-85-8  Y
3D model (JSmol)	Interactive image
Beilstein Reference	605190
ChEBI	CHEBI:15437
ChemSpider	1146
Gmelin Reference	1166130
KEGG	C01051
MeSH	Uroporphyrinogen+III
PubChem CID	1179
CompTox Dashboard (EPA)	DTXSID40173444
InChI InChI=1S/C40H44N4O16/c45-33(46)5-1-17-21(9-37(53)54)29-14-27-19(3-7-35(49)50)22(10-38(55)56)30(43-27)15-28-20(4-8-36(51)52)24(12-40(59)60)32(44-28)16-31-23(11-39(57)58)18(2-6-34(47)48)26(42-31)13-25(17)41-29/h41-44H,1-16H2,(H,45,46)(H,47,48)(H,49,50)(H,51,52)(H,53,54)(H,55,56)(H,57,58)(H,59,60) Key: HUHWZXWWOFSFKF-UHFFFAOYSA-N
SMILES O=C(O)CCc1c2[nH]c(c1CC(=O)O)Cc1[nH]c(c(CC(=O)O)c1CCC(=O)O)Cc1[nH]c(c(CC(=O)O)c1CCC(=O)O)Cc1[nH]c(c(CCC(=O)O)c1CC(=O)O)C2
Properties
Chemical formula	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 (−CH₂−COOH, "A") and a propionic acid group (−CH₂−CH₂−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]}

hydroxymethylbilane

 

 

H₂O

 

H₂O

 

uroporphyrinogen III

In the biosynthesis of hemes and chlorophylls, uroporphyrinogen III is converted into coproporphyrinogen III by the enzyme uroporphyrinogen III decarboxylase. ^[6]

uroporphyrinogen III

 

 

4 CO₂

 

4 CO₂

 

coproporphyrinogen III

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

• Uroporphyrinogen

References

1. Dalton, J (1969). "Formation of the Macrocyclic Ring in Tetrapyrrole Biosynthesis". Nature. 223 (5211): 1151–1153. Bibcode:1969Natur.223.1151D. doi:10.1038/2231151a0. PMID   5810686. S2CID   4177167.
2. 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. Bibcode:1980Natur.285...17B. doi:10.1038/285017a0. PMID   6769048. S2CID   9070849.
3. Enzyme 4.2.1.75 at KEGG Pathway Database.
4. Paul R. Ortiz de Montellano (2008). "Hemes in Biology". Wiley Encyclopedia of Chemical Biology. John Wiley & Sons. pp. 1–10. doi:10.1002/9780470048672.wecb221. ISBN   978-0-470-04867-2.
5. 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
6. 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.