2.02012-05-31 13:44:54 -06002015-06-03 15:53:43 -0600ECMDB01086M2MDB000248Uroporphyrinogen IIIUroporphyrinogens are porphyrinogen variants in which each pyrrole ring has one acetate side chain and one propionate side chain; it is formed by condensation 4 four molecules of porphobilinogen. 4 isomers are possible but only 2 commoly are found, types I and III. Uroporphyrinogen III is a functional intermediate in heme biosynthesis while Uroporphyrinogen I is produced in an abortive side reaction.3,8,13,17-Tetrakis(carboxymethyl)-5,10,15,20,22,24-hexahydro-2,7,12,18-Porphinetetrapropionate3,8,13,17-Tetrakis(carboxymethyl)-5,10,15,20,22,24-hexahydro-2,7,12,18-Porphinetetrapropionic acid3,8,13,17-Tetrakis(carboxymethyl)-5,10,15,20,22,24-hexahydro-21H,23H-Porphine-2,7,12,18-tetrapropanoate3,8,13,17-Tetrakis(carboxymethyl)-5,10,15,20,22,24-hexahydro-21H,23H-Porphine-2,7,12,18-tetrapropanoic acid3,8,13,17-Tetrakis(carboxymethyl)-5,10,15,20,22,24-hexahydroporphyrin-2,7,12,18-tetrapropanoate3,8,13,17-Tetrakis(carboxymethyl)-5,10,15,20,22,24-hexahydroporphyrin-2,7,12,18-tetrapropanoic acidUrogen IUrogen IIIUroPorgen-IIIUroporphyrinogen IUroporphyrinogen IIIUroporphyrinogen-IIIC40H44N4O16836.7946836.275231383-[9,14,20-tris(2-carboxyethyl)-5,10,15,19-tetrakis(carboxymethyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1(20),3,5,8,10,13,15,18-octaen-4-yl]propanoic aciduroporphyrinogen-III1976-85-8OC(=O)CCC1=C2CC3=C(CCC(O)=O)C(CC(O)=O)=C(CC4=C(CC(O)=O)C(CCC(O)=O)=C(CC5=C(CC(O)=O)C(CCC(O)=O)=C(CC(N2)=C1CC(O)=O)N5)N4)N3InChI=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)HUHWZXWWOFSFKF-UHFFFAOYSA-NSolidCytosollogp0.67logs-4.28solubility4.37e-02 g/llogp1.39pka_strongest_acidic3.21iupac3-[9,14,20-tris(2-carboxyethyl)-5,10,15,19-tetrakis(carboxymethyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1(20),3,5,8,10,13,15,18-octaen-4-yl]propanoic acidaverage_mass836.7946mono_mass836.27523138smilesOC(=O)CCC1=C2CC3=C(CCC(O)=O)C(CC(O)=O)=C(CC4=C(CC(O)=O)C(CCC(O)=O)=C(CC5=C(CC(O)=O)C(CCC(O)=O)=C(CC(N2)=C1CC(O)=O)N5)N4)N3formulaC40H44N4O16inchiInChI=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)inchikeyHUHWZXWWOFSFKF-UHFFFAOYSA-Npolar_surface_area361.56refractivity206.93polarizability81.55rotatable_bond_count20acceptor_count16donor_count12physiological_charge-8formal_charge0Porphyrin and chlorophyll metabolismec00860Metabolic pathwayseco01100Porphyrin metabolismThe metabolism of porphyrin begins with with glutamic acid being processed by an ATP-driven glutamyl-tRNA synthetase by interacting with hydrogen ion and tRNA(Glu), resulting in amo, pyrophosphate and L-glutamyl-tRNA(Glu) Glutamic acid. Glutamic acid can be obtained as a result of L-glutamate metabolism pathway, glutamate / aspartate : H+ symporter GltP, glutamate:sodium symporter or a glutamate / aspartate ABC transporter .
L-glutamyl-tRNA(Glu) Glutamic acid interacts with a NADPH glutamyl-tRNA reductase resulting in a NADP, a tRNA(Glu) and a (S)-4-amino-5-oxopentanoate.
This compound interacts with a glutamate-1-semialdehyde aminotransferase resulting a 5-aminolevulinic acid. This compound interacts with a porphobilinogen synthase resulting in a hydrogen ion, water and porphobilinogen. The latter compound interacts with water resulting in hydroxymethylbilane synthase resulting in ammonium, and hydroxymethylbilane.
Hydroxymethylbilane can either be dehydrated to produce uroporphyrinogen I or interact with a uroporphyrinogen III synthase resulting in a water molecule and a uroporphyrinogen III.
Uroporphyrinogen I interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a coproporphyrinogen I
Uroporphyrinogen III can be metabolized into precorrin by interacting with a S-adenosylmethionine through a siroheme synthase resulting in hydrogen ion, an s-adenosylhomocysteine and a precorrin-1. On the other hand, Uroporphyrinogen III interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a Coproporphyrinogen III.
Precorrin-1 reacts with a S-adenosylmethionine through a siroheme synthase resulting in a S-adenosylhomocysteine and a Precorrin-2. The latter compound is processed by a NAD dependent uroporphyrin III C-methyltransferase [multifunctional] resulting in a NADH and a sirohydrochlorin. This compound then interacts with Fe 2+
uroporphyrin III C-methyltransferase [multifunctional] resulting in a hydrogen ion and a siroheme. The siroheme is then processed in sulfur metabolism pathway.
Uroporphyrinogen III can be processed in anaerobic or aerobic condition.
Anaerobic:
Uroporphyrinogen III interacts with an oxygen molecule, a hydrogen ion through a coproporphyrinogen III oxidase resulting in water, carbon dioxide and protoporphyrinogen IX. The latter compound then interacts with an 3 oxygen molecule through a protoporphyrinogen oxidase resulting in 3 hydrogen peroxide and a Protoporphyrin IX
Aerobic:
Uroporphyrinogen III reacts with S-adenosylmethionine through a coproporphyrinogen III dehydrogenase resulting in carbon dioxide, 5-deoxyadenosine, L-methionine and protoporphyrinogen IX. The latter compound interacts with a meanquinone through a protoporphyrinogen oxidase resulting in protoporphyrin IX.
The protoporphyrin IX interacts with Fe 2+ through a ferrochelatase resulting in a hydrogen ion and a ferroheme b. The ferroheme b can either be incorporated into the oxidative phosphorylation as a cofactor of the enzymes involved in that pathway or it can interact with hydrogen peroxide through a catalase HPII resulting in a heme D. Heme D can then be incorporated into the oxidative phosphyrlation pathway as a cofactor of the enzymes involved in that pathway. Ferroheme b can also interact with water and a farnesyl pyrophosphate through a heme O synthase resulting in a release of pyrophosphate and heme O. Heme O is then incorporated into the Oxidative phosphorylation pathway.
PW000936Metabolictetrapyrrole biosynthesis IPWY-5188heme biosynthesis from uroporphyrinogen-III IHEME-BIOSYNTHESIS-IIsuperpathway of heme biosynthesis from uroporphyrinogen-IIIPWY0-1415heme biosynthesis from uroporphyrinogen-III IIHEMESYN2-PWYsiroheme biosynthesisPWY-5194Specdb::EiMs5383Specdb::NmrOneD345048Specdb::NmrOneD345049Specdb::NmrOneD345050Specdb::NmrOneD345051Specdb::NmrOneD345052Specdb::NmrOneD345053Specdb::NmrOneD345054Specdb::NmrOneD345055Specdb::NmrOneD345056Specdb::NmrOneD345057Specdb::NmrOneD345058Specdb::NmrOneD345059Specdb::NmrOneD345060Specdb::NmrOneD345061Specdb::NmrOneD345062Specdb::NmrOneD345063Specdb::NmrOneD345064Specdb::NmrOneD345065Specdb::NmrOneD345066Specdb::NmrOneD345067Specdb::MsMs29585Specdb::MsMs29586Specdb::MsMs29587Specdb::MsMs36143Specdb::MsMs36144Specdb::MsMs36145Specdb::MsMs2375444Specdb::MsMs2375445Specdb::MsMs2375446Specdb::MsMs2559426Specdb::MsMs2559427Specdb::MsMs2559428HMDB0108611791146C0105115437UROPORPHYRINOGEN-IIIUP2Uroporphyrinogen IIIKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Aizencang G, Solis C, Bishop DF, Warner C, Desnick RJ: Human uroporphyrinogen-III synthase: genomic organization, alternative promoters, and erythroid-specific expression. Genomics. 2000 Dec 1;70(2):223-31.11112350Martins BM, Grimm B, Mock HP, Huber R, Messerschmidt A: Crystal structure and substrate binding modeling of the uroporphyrinogen-III decarboxylase from Nicotiana tabacum. Implications for the catalytic mechanism. J Biol Chem. 2001 Nov 23;276(47):44108-16. Epub 2001 Aug 27.11524417Uroporphyrinogen-III synthaseP09126HEM4_ECOLIhemDhttp://ecmdb.ca/proteins/P09126.xmlPutative uroporphyrinogen-III C-methyltransferaseP09127HEMX_ECOLIhemXhttp://ecmdb.ca/proteins/P09127.xmlSiroheme synthaseP0AEA8CYSG_ECOLIcysGhttp://ecmdb.ca/proteins/P0AEA8.xmlUroporphyrinogen decarboxylaseP29680DCUP_ECOLIhemEhttp://ecmdb.ca/proteins/P29680.xml2 S-Adenosylmethionine + Uroporphyrinogen III >2 S-Adenosylhomocysteine + Precorrin 2 + Hydrogen ionR03194Hydroxymethylbilane <> Water + Uroporphyrinogen IIIR03165UROGENIIISYN-RXN4 Hydrogen ion + Uroporphyrinogen III <>4 Carbon dioxide + Coproporphyrin IIIR031972 S-Adenosylmethionine + Uroporphyrinogen III <>2 S-Adenosylhomocysteine + Precorrin 2R03194Uroporphyrinogen III <> Coproporphyrin III +4 Carbon dioxideR03197S-Adenosylmethionine + Uroporphyrinogen III <> S-Adenosylhomocysteine + precorrin-1 + Hydrogen ionUROPORIIIMETHYLTRANSA-RXNHydrogen ion + Uroporphyrinogen III > Carbon dioxide + Coproporphyrinogen IIIUROGENDECARBOX-RXNS-adenosyl-L-methionine + Uroporphyrinogen III > S-Adenosylhomocysteine + Precorrin-1Uroporphyrinogen III > Coproporphyrinogen III +4 Carbon dioxideHydroxymethylbilane > Uroporphyrinogen III + Water2 S-Adenosylmethionine + Uroporphyrinogen III + Precorrin-1 <>2 S-Adenosylhomocysteine + Precorrin 2R03194 Uroporphyrinogen III + 4 Hydrogen ion >4 Carbon dioxide + Coproporphyrinogen IIIPW_R003480Uroporphyrinogen III + S-adenosyl-L-methionine > Hydrogen ion + S-Adenosylhomocysteine + Precorrin-1PW_R0034892 S-Adenosylmethionine + Uroporphyrinogen III >2 S-Adenosylhomocysteine + Precorrin 2 + Hydrogen ion4 Hydrogen ion + Uroporphyrinogen III <>4 Carbon dioxide + Coproporphyrin IIIHydroxymethylbilane <> Water + Uroporphyrinogen III2 S-Adenosylmethionine + Uroporphyrinogen III >2 S-Adenosylhomocysteine + Precorrin 2 + Hydrogen ion