2.0 2012-05-31 13:45:13 -0600 2015-06-03 15:53:44 -0600 ECMDB01097 M2MDB000254 Protoporphyrinogen IX Protoporphyrinogen IX is an intermediate in heme biosynthesis. It is a porphyrinogen in which 2 pyrrole rings each have one methyl and one propionate side chain and the other two pyrrole rings each have one methyl and one vinyl side chain. 15 isomers are possible but only one, type IX, occurs naturally. Protoporphyrinogen is produced by oxidative decarboxylation of coproporphyrinogen. 5,10,15,20,22,24-Hexahydro protoporphyrin IX deriv. 7,12-Diethenyl-3,8,13,17-tetramethyl-5,10,15,20,22,24-hexahydroporphyrin-2,18-dipropanoate 7,12-Diethenyl-3,8,13,17-tetramethyl-5,10,15,20,22,24-hexahydroporphyrin-2,18-dipropanoic acid 7,12-Diethenyl-5,10,15,20,22,24-hexahydro-3,8,13,17-tetramethyl-21h,23h-porphine-2,18-dipropanoate 7,12-Diethenyl-5,10,15,20,22,24-hexahydro-3,8,13,17-tetramethyl-21h,23h-porphine-2,18-dipropanoic acid Protoporphyrinogen Protoporphyrinogen IX Protoporphyrinogen-IX C34H40N4O4 568.7058 568.304955788 3-[20-(2-carboxyethyl)-9,14-diethenyl-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(20),3,5,8,10,13,15,18-octaen-4-yl]propanoic acid 3-[20-(2-carboxyethyl)-9,14-diethenyl-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(20),3,5,8,10,13,15,18-octaen-4-yl]propanoic acid 7412-77-3 CC1=C2CC3=C(C)C(C=C)=C(CC4=C(C)C(C=C)=C(CC5=C(C)C(CCC(O)=O)=C(CC(N2)=C1CCC(O)=O)N5)N4)N3 InChI=1S/C34H40N4O4/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25/h7-8,35-38H,1-2,9-16H2,3-6H3,(H,39,40)(H,41,42) UHSGPDMIQQYNAX-UHFFFAOYSA-N Solid Cytosol Membrane logp 3.44 ALOGPS logs -5.01 ALOGPS solubility 5.51e-03 g/l ALOGPS logp 6.2 ChemAxon pka_strongest_acidic 4.07 ChemAxon iupac 3-[20-(2-carboxyethyl)-9,14-diethenyl-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(20),3,5,8,10,13,15,18-octaen-4-yl]propanoic acid ChemAxon average_mass 568.7058 ChemAxon mono_mass 568.304955788 ChemAxon smiles CC1=C2CC3=C(C)C(C=C)=C(CC4=C(C)C(C=C)=C(CC5=C(C)C(CCC(O)=O)=C(CC(N2)=C1CCC(O)=O)N5)N4)N3 ChemAxon formula C34H40N4O4 ChemAxon inchi InChI=1S/C34H40N4O4/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25/h7-8,35-38H,1-2,9-16H2,3-6H3,(H,39,40)(H,41,42) ChemAxon inchikey UHSGPDMIQQYNAX-UHFFFAOYSA-N ChemAxon polar_surface_area 137.76 ChemAxon refractivity 169.42 ChemAxon polarizability 64.52 ChemAxon rotatable_bond_count 8 ChemAxon acceptor_count 4 ChemAxon donor_count 6 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Porphyrin and chlorophyll metabolism ec00860 Metabolic pathways eco01100 Porphyrin metabolism The 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. PW000936 Metabolic heme biosynthesis from uroporphyrinogen-III I HEME-BIOSYNTHESIS-II superpathway of heme biosynthesis from uroporphyrinogen-III PWY0-1415 heme biosynthesis from uroporphyrinogen-III II HEMESYN2-PWY Specdb::CMs 13213 Specdb::CMs 37925 Specdb::CMs 282200 Specdb::CMs 365535 Specdb::CMs 365536 Specdb::CMs 365537 Specdb::CMs 365538 Specdb::CMs 365539 Specdb::CMs 365540 Specdb::CMs 365541 Specdb::CMs 365542 Specdb::CMs 365543 Specdb::CMs 365544 Specdb::CMs 365545 Specdb::CMs 365546 Specdb::CMs 365547 Specdb::CMs 365548 Specdb::CMs 365549 Specdb::CMs 365550 Specdb::CMs 365551 Specdb::CMs 365552 Specdb::CMs 365553 Specdb::CMs 365554 Specdb::CMs 365555 Specdb::CMs 365556 Specdb::NmrOneD 281599 Specdb::NmrOneD 281600 Specdb::NmrOneD 281601 Specdb::NmrOneD 281602 Specdb::NmrOneD 281603 Specdb::NmrOneD 281604 Specdb::NmrOneD 281605 Specdb::NmrOneD 281606 Specdb::NmrOneD 281607 Specdb::NmrOneD 281608 Specdb::NmrOneD 281609 Specdb::NmrOneD 281610 Specdb::NmrOneD 281611 Specdb::NmrOneD 281612 Specdb::NmrOneD 281613 Specdb::NmrOneD 281614 Specdb::NmrOneD 281615 Specdb::NmrOneD 281616 Specdb::NmrOneD 281617 Specdb::NmrOneD 281618 Specdb::MsMs 26588 Specdb::MsMs 26589 Specdb::MsMs 26590 Specdb::MsMs 33146 Specdb::MsMs 33147 Specdb::MsMs 33148 Specdb::MsMs 2468344 Specdb::MsMs 2468345 Specdb::MsMs 2468346 Specdb::MsMs 2497772 Specdb::MsMs 2497773 Specdb::MsMs 2497774 HMDB01097 121893 108741 C01079 15435 PROTOPORPHYRINOGEN Protoporphyrinogen IX Keseler, 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. 21097882 Kanehisa, 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. 22080510 van 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. 17765195 Winder, 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. 18331064 Wan J, Zhang L, Yang G, Zhan CG: Quantitative structure-activity relationship for cyclic imide derivatives of protoporphyrinogen oxidase inhibitors: a study of quantum chemical descriptors from density functional theory. J Chem Inf Comput Sci. 2004 Nov-Dec;44(6):2099-105. 15554680 Herrick AL, Moore MR, Thompson GG, Ford GP, McColl KE: Cholelithiasis in patients with variegate porphyria. J Hepatol. 1991 Jan;12(1):50-3. 2007776 Krijt J, Stranska P, Maruna P, Vokurka M, Sanitrak J: Herbicide-induced experimental variegate porphyria in mice: tissue porphyrinogen accumulation and response to porphyrogenic drugs. Can J Physiol Pharmacol. 1997 Oct-Nov;75(10-11):1181-7. 9431441 Bloomer JR: Enzyme defects in the porphyrias and their relevance to the biochemical abnormalities in these disorders. 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Lancet. 2005 Jul 23-29;366(9482):332-5. 16039338 Protoporphyrinogen oxidase P0ACB4 HEMG_ECOLI hemG http://ecmdb.ca/proteins/P0ACB4.xml Oxygen-independent coproporphyrinogen-III oxidase P32131 HEMN_ECOLI hemN http://ecmdb.ca/proteins/P32131.xml Coproporphyrinogen-III oxidase, aerobic P36553 HEM6_ECOLI hemF http://ecmdb.ca/proteins/P36553.xml Oxygen-independent coproporphyrinogen-III oxidase-like protein yggW P52062 YGGW_ECOLI yggW http://ecmdb.ca/proteins/P52062.xml Coproporphyrin III + 2 Hydrogen ion + Oxygen <>2 Carbon dioxide +2 Water + Protoporphyrinogen IX R03220 Oxygen + Protoporphyrinogen IX >3 Water + Protoporphyrin IX 3 Fumaric acid + Protoporphyrinogen IX > Protoporphyrin IX +3 Succinic acid 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX R06895 Coproporphyrin III + Oxygen <> Protoporphyrinogen IX +2 Carbon dioxide +2 Water R03220 Protoporphyrinogen IX + 3 Menaquinone + 3 Menaquinone <> Protoporphyrin IX +3 Menaquinol 6 R09489 Coproporphyrinogen III + S-Adenosylmethionine > Protoporphyrinogen IX + Carbon dioxide + L-Methionine + 5'-Deoxyadenosine HEMN-RXN Protoporphyrinogen IX + Oxygen > Protoporphyrin IX + Hydrogen peroxide PROTOPORGENOXI-RXN Coproporphyrinogen III + Oxygen + Hydrogen ion > Protoporphyrinogen IX + Carbon dioxide + Water RXN0-1461 Protoporphyrinogen IX + a menaquinone > Protoporphyrin IX + a menaquinol RXN0-6259 Coproporphyrinogen III + Oxygen + 2 Hydrogen ion > Protoporphyrinogen IX +2 Carbon dioxide +2 Water RXN0-1461 Protoporphyrinogen IX + 3 Menaquinone > Protoporphyrin IX +3 Menaquinol 6 R09489 Coproporphyrinogen III + 2 S-adenosyl-L-methionine > Protoporphyrinogen IX +2 Carbon dioxide +2 L-Methionine +2 5'-Deoxyadenosine Protoporphyrinogen IX + 3 Oxygen <> Protoporphyrin IX +3 Hydrogen peroxide R03222 S-adenosyl-L-methionine + Coproporphyrinogen III > 5'-Deoxyadenosine + L-Methionine + Carbon dioxide + Protoporphyrinogen IX PW_R003483 Protoporphyrinogen IX + 3 Oxygen > Protoporphyrin IX +3 Hydrogen peroxide PW_R003484 Protoporphyrinogen IX + menaquinone-8 > Protoporphyrin IX + Menaquinol 6 PW_R003485 Coproporphyrin III + 2 Hydrogen ion + Oxygen <>2 Carbon dioxide +2 Water + Protoporphyrinogen IX 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX 2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX