2.0 2012-05-31 10:24:48 -0600 2015-09-13 12:56:07 -0600 ECMDB00245 M2MDB000104 Porphobilinogen Porphobilinogen is a pyrrole involved in porphyrin metabolism. -- Wikipedia; It consists of a pyrrole ring with acetyl, propionyl, and aminomethyl side chains; It is a key monopyrrolic intermediate in porphyrin, chlorophyll and vitamin B12 biosynthesis. Porphobilinogen is generated by the enzyme ALA dehydratase by combining two molecules of dALA together, and converted into hydroxymethyl bilane by the enzyme porphobilinogen deaminase. 4 molecules of porphobilinogen are condensed to form one molecule of uroporphyrinogen I, which is then converted successively to coproporphyrinogen I, protoporphyrin IX, and heme. 5-(Aminomethyl)-4-(carboxymethyl)-Pyrrole-3-propionate 5-(Aminomethyl)-4-(carboxymethyl)-Pyrrole-3-propionic acid PBG Porphobilinogen C10H14N2O4 226.2292 226.095356946 3-[5-(aminomethyl)-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acid porphobilinogen 487-90-1 NCC1=C(CC(O)=O)C(CCC(O)=O)=CN1 InChI=1S/C10H14N2O4/c11-4-8-7(3-10(15)16)6(5-12-8)1-2-9(13)14/h5,12H,1-4,11H2,(H,13,14)(H,15,16) QSHWIQZFGQKFMA-UHFFFAOYSA-N Solid Cytosol logp -2.40 ALOGPS logs -1.92 ALOGPS solubility 2.72e+00 g/l ALOGPS logp -2.7 ChemAxon pka_strongest_acidic 3.66 ChemAxon pka_strongest_basic 8.78 ChemAxon iupac 3-[5-(aminomethyl)-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acid ChemAxon average_mass 226.2292 ChemAxon mono_mass 226.095356946 ChemAxon smiles NCC1=C(CC(O)=O)C(CCC(O)=O)=CN1 ChemAxon formula C10H14N2O4 ChemAxon inchi InChI=1S/C10H14N2O4/c11-4-8-7(3-10(15)16)6(5-12-8)1-2-9(13)14/h5,12H,1-4,11H2,(H,13,14)(H,15,16) ChemAxon inchikey QSHWIQZFGQKFMA-UHFFFAOYSA-N ChemAxon polar_surface_area 116.41 ChemAxon refractivity 56.38 ChemAxon polarizability 22.56 ChemAxon rotatable_bond_count 6 ChemAxon acceptor_count 5 ChemAxon donor_count 4 ChemAxon physiological_charge -1 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 tetrapyrrole biosynthesis I PWY-5188 Specdb::CMs 1965 Specdb::CMs 2545 Specdb::CMs 31101 Specdb::CMs 37384 Specdb::CMs 173746 Specdb::CMs 1055294 Specdb::CMs 1055296 Specdb::CMs 1055298 Specdb::CMs 1055300 Specdb::CMs 1055301 Specdb::CMs 1055303 Specdb::CMs 1055305 Specdb::CMs 1055307 Specdb::CMs 1055309 Specdb::CMs 1055311 Specdb::CMs 1055312 Specdb::CMs 1055314 Specdb::CMs 1055316 Specdb::CMs 1055318 Specdb::CMs 1055320 Specdb::CMs 1055322 Specdb::CMs 1055323 Specdb::CMs 1055325 Specdb::CMs 1055327 Specdb::CMs 1055329 Specdb::NmrOneD 143190 Specdb::NmrOneD 143191 Specdb::NmrOneD 143192 Specdb::NmrOneD 143193 Specdb::NmrOneD 143194 Specdb::NmrOneD 143195 Specdb::NmrOneD 143196 Specdb::NmrOneD 143197 Specdb::NmrOneD 143198 Specdb::NmrOneD 143199 Specdb::NmrOneD 143200 Specdb::NmrOneD 143201 Specdb::NmrOneD 143202 Specdb::NmrOneD 143203 Specdb::NmrOneD 143204 Specdb::NmrOneD 143205 Specdb::NmrOneD 143206 Specdb::NmrOneD 143207 Specdb::NmrOneD 143208 Specdb::NmrOneD 143209 Specdb::MsMs 415 Specdb::MsMs 416 Specdb::MsMs 417 Specdb::MsMs 21143 Specdb::MsMs 21144 Specdb::MsMs 21145 Specdb::MsMs 22694 Specdb::MsMs 22695 Specdb::MsMs 22696 Specdb::MsMs 1471172 Specdb::MsMs 1471192 Specdb::MsMs 1471325 Specdb::MsMs 1471885 Specdb::MsMs 1471886 Specdb::MsMs 1471887 Specdb::MsMs 1471888 Specdb::MsMs 1471889 Specdb::MsMs 1471890 Specdb::MsMs 1471891 Specdb::MsMs 1471892 Specdb::MsMs 1471893 Specdb::MsMs 1471894 Specdb::MsMs 1471895 Specdb::MsMs 1471896 Specdb::MsMs 1471897 HMDB00245 1021 995 C00931 17381 PORPHOBILINOGEN PBG Porphobilinogen 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 Dhar GJ, Bossenmaier I, Petryka ZJ, Cardinal R, Watson CJ: Effects of hematin in hepatic porphyria. Further studies. Ann Intern Med. 1975 Jul;83(1):20-30. 1147435 Ivanov E, Pisanets M: Studies on the biosynthesis of porphyrins in erythrocytes after incubation with delta-aminolevulinic acid: an attempt to investigate the pathogenesis of nephrogenic anemia. Acta Biol Med Ger. 1982;41(4):307-13. 7124248 Ellencweig N, Schoenfeld N, Zemishlany Z: Acute intermittent porphyria: psychosis as the only clinical manifestation. Isr J Psychiatry Relat Sci. 2006;43(1):52-6. 16910386 Buchet JP, Lauwerys R, Hassoun A, Dratwa M, Wens R, Collart F, Tielemans C: Effect of aluminum on porphyrin metabolism in hemodialyzed patients. Nephron. 1987;46(4):360-3. 3658064 Tishler PV, Woodward B, O'Connor J, Holbrook DA, Seidman LJ, Hallett M, Knighton DJ: High prevalence of intermittent acute porphyria in a psychiatric patient population. Am J Psychiatry. 1985 Dec;142(12):1430-6. 4073306 Hsiao KJ, Lee FY, Wu SJ, Chang WJ: Determination of erythrocyte porphobilinogen deaminase activity using porphobilinogen as substrate. Clin Chim Acta. 1987 Sep 30;168(2):257-8. 3677422 Evans J, Lefkowitch J, Lim CK, Billing B: Fecal porphyrin abnormalities in a patient with features of Rotor's syndrome. Gastroenterology. 1981 Dec;81(6):1125-30. 7286590 Sassa S, Solish G, Levere RD, Kappas A: Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait. J Exp Med. 1975 Sep 1;142(3):722-31. 1165472 Ford RE, Ou CN, Ellefson RD: Assay for erythrocyte uroporphyrinogen I synthase activity, with porphobilinogen as substrate. Clin Chem. 1980 Jul;26(8):1182-5. 7389090 Shiue JW, Lee FY, Hsiao KJ, Tsai YT, Lee SD, Wu SJ: Abnormal thyroid function and hypercholesterolemia in a case of acute intermittent porphyria. Taiwan Yi Xue Hui Za Zhi. 1989 Jul;88(7):729-31. 2809566 Mustajoki P: Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria. Ann Intern Med. 1981 Aug;95(2):162-6. 7258864 Frydman, Benjamin; Despuy, Maria E.; Rapoport, Henry. Pyrroles from azaindoles. A synthesis of porphobilinogen. Journal of the American Chemical Society (1965), 87(15), 3530-1. http://hmdb.ca/system/metabolites/msds/000/000/179/original/HMDB00245.pdf?1358462154 Porphobilinogen deaminase P06983 HEM3_ECOLI hemC http://ecmdb.ca/proteins/P06983.xml Delta-aminolevulinic acid dehydratase P0ACB2 HEM2_ECOLI hemB http://ecmdb.ca/proteins/P0ACB2.xml 2 5-Aminolevulinic acid <> Hydrogen ion +2 Water + Porphobilinogen R00036 PORPHOBILSYNTH-RXN Water + 4 Porphobilinogen > Hydroxymethylbilane +4 Ammonium 2 5-Aminolevulinic acid <> Porphobilinogen +2 Water R00036 4 Porphobilinogen + Water <> Hydroxymethylbilane +4 Ammonia R00084 OHMETHYLBILANESYN-RXN Water + Porphobilinogen <> Hydrogen ion + Ammonia + Hydroxymethylbilane OHMETHYLBILANESYN-RXN 5-Aminolevulinic acid <> Hydrogen ion + Water + Porphobilinogen R00036 PORPHOBILSYNTH-RXN 2 5-Aminolevulinic acid > Porphobilinogen +2 Water 4 Porphobilinogen + Water > Hydroxymethylbilane +4 Ammonia R00084 OHMETHYLBILANESYN-RXN 8 5-Aminolevulinic acid >4 Hydrogen ion +8 Water +4 Porphobilinogen PW_R003475 2 5-Aminolevulinic acid <> Hydrogen ion +2 Water + Porphobilinogen 2 5-Aminolevulinic acid <> Porphobilinogen +2 Water 4 Porphobilinogen + Water <> Hydroxymethylbilane +4 Ammonia 2 5-Aminolevulinic acid <> Hydrogen ion +2 Water + Porphobilinogen 4 Porphobilinogen + Water <> Hydroxymethylbilane +4 Ammonia