2.02012-05-31 10:24:48 -06002015-09-13 12:56:07 -0600ECMDB00245M2MDB000104PorphobilinogenPorphobilinogen 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-propionate5-(Aminomethyl)-4-(carboxymethyl)-Pyrrole-3-propionic acidPBGPorphobilinogenC10H14N2O4226.2292226.0953569463-[5-(aminomethyl)-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acidporphobilinogen487-90-1NCC1=C(CC(O)=O)C(CCC(O)=O)=CN1InChI=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-NSolidCytosollogp-2.40logs-1.92solubility2.72e+00 g/llogp-2.7pka_strongest_acidic3.66pka_strongest_basic8.78iupac3-[5-(aminomethyl)-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acidaverage_mass226.2292mono_mass226.095356946smilesNCC1=C(CC(O)=O)C(CCC(O)=O)=CN1formulaC10H14N2O4inchiInChI=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)inchikeyQSHWIQZFGQKFMA-UHFFFAOYSA-Npolar_surface_area116.41refractivity56.38polarizability22.56rotatable_bond_count6acceptor_count5donor_count4physiological_charge-1formal_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-5188Specdb::CMs1965Specdb::CMs2545Specdb::CMs31101Specdb::CMs37384Specdb::CMs173746Specdb::CMs1055294Specdb::CMs1055296Specdb::CMs1055298Specdb::CMs1055300Specdb::CMs1055301Specdb::CMs1055303Specdb::CMs1055305Specdb::CMs1055307Specdb::CMs1055309Specdb::CMs1055311Specdb::CMs1055312Specdb::CMs1055314Specdb::CMs1055316Specdb::CMs1055318Specdb::CMs1055320Specdb::CMs1055322Specdb::CMs1055323Specdb::CMs1055325Specdb::CMs1055327Specdb::CMs1055329Specdb::NmrOneD143190Specdb::NmrOneD143191Specdb::NmrOneD143192Specdb::NmrOneD143193Specdb::NmrOneD143194Specdb::NmrOneD143195Specdb::NmrOneD143196Specdb::NmrOneD143197Specdb::NmrOneD143198Specdb::NmrOneD143199Specdb::NmrOneD143200Specdb::NmrOneD143201Specdb::NmrOneD143202Specdb::NmrOneD143203Specdb::NmrOneD143204Specdb::NmrOneD143205Specdb::NmrOneD143206Specdb::NmrOneD143207Specdb::NmrOneD143208Specdb::NmrOneD143209Specdb::MsMs415Specdb::MsMs416Specdb::MsMs417Specdb::MsMs21143Specdb::MsMs21144Specdb::MsMs21145Specdb::MsMs22694Specdb::MsMs22695Specdb::MsMs22696Specdb::MsMs1471172Specdb::MsMs1471192Specdb::MsMs1471325Specdb::MsMs1471885Specdb::MsMs1471886Specdb::MsMs1471887Specdb::MsMs1471888Specdb::MsMs1471889Specdb::MsMs1471890Specdb::MsMs1471891Specdb::MsMs1471892Specdb::MsMs1471893Specdb::MsMs1471894Specdb::MsMs1471895Specdb::MsMs1471896Specdb::MsMs1471897HMDB002451021995C0093117381PORPHOBILINOGENPBGPorphobilinogenKeseler, 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 80:2939-2948.18331064Dhar GJ, Bossenmaier I, Petryka ZJ, Cardinal R, Watson CJ: Effects of hematin in hepatic porphyria. Further studies. Ann Intern Med. 1975 Jul;83(1):20-30.1147435Ivanov 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):307-13.7124248Ellencweig N, Schoenfeld N, Zemishlany Z: Acute intermittent porphyria: psychosis as the only clinical manifestation. Isr J Psychiatry Relat Sci. 2006;43(1):52-6.16910386Buchet 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):360-3.3658064Tishler 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):1430-6.4073306Hsiao 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):257-8.3677422Evans J, Lefkowitch J, Lim CK, Billing B: Fecal porphyrin abnormalities in a patient with features of Rotor's syndrome. Gastroenterology. 1981 Dec;81(6):1125-30.7286590Sassa 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):722-31.1165472Ford RE, Ou CN, Ellefson RD: Assay for erythrocyte uroporphyrinogen I synthase activity, with porphobilinogen as substrate. Clin Chem. 1980 Jul;26(8):1182-5.7389090Shiue 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):729-31.2809566Mustajoki P: Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria. Ann Intern Med. 1981 Aug;95(2):162-6.7258864Frydman, 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?1358462154Porphobilinogen deaminaseP06983HEM3_ECOLIhemChttp://ecmdb.ca/proteins/P06983.xmlDelta-aminolevulinic acid dehydrataseP0ACB2HEM2_ECOLIhemBhttp://ecmdb.ca/proteins/P0ACB2.xml2 5-Aminolevulinic acid <> Hydrogen ion +2 Water + PorphobilinogenR00036PORPHOBILSYNTH-RXNWater + 4 Porphobilinogen > Hydroxymethylbilane +4 Ammonium2 5-Aminolevulinic acid <> Porphobilinogen +2 WaterR000364 Porphobilinogen + Water <> Hydroxymethylbilane +4 AmmoniaR00084OHMETHYLBILANESYN-RXNWater + Porphobilinogen <> Hydrogen ion + Ammonia + HydroxymethylbilaneOHMETHYLBILANESYN-RXN5-Aminolevulinic acid <> Hydrogen ion + Water + PorphobilinogenR00036PORPHOBILSYNTH-RXN2 5-Aminolevulinic acid > Porphobilinogen +2 Water4 Porphobilinogen + Water > Hydroxymethylbilane +4 AmmoniaR00084OHMETHYLBILANESYN-RXN8 5-Aminolevulinic acid >4 Hydrogen ion +8 Water +4 PorphobilinogenPW_R0034752 5-Aminolevulinic acid <> Hydrogen ion +2 Water + Porphobilinogen2 5-Aminolevulinic acid <> Porphobilinogen +2 Water4 Porphobilinogen + Water <> Hydroxymethylbilane +4 Ammonia2 5-Aminolevulinic acid <> Hydrogen ion +2 Water + Porphobilinogen4 Porphobilinogen + Water <> Hydroxymethylbilane +4 Ammonia