2.02012-05-31 14:32:32 -06002015-06-03 17:19:30 -0600ECMDB20195M2MDB001041SirohydrochlorinSirohydrochlorin is a member of the chemical class known as Precorrins. These are intermediates formed by methylation at one or more of the four rings prior to the formation of the macrocyclic corrin ring. typhimurium, precorrin-2 is a precursor of both siroheme and B12. (PMID 8955319)PrecorrinC42H46N4O16862.8318862.2908814443-[(4S,5S,9S,10S)-9,15,19-tris(2-carboxyethyl)-5,10,14,20-tetrakis(carboxymethyl)-5,10-dimethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1(21),2,6,8(23),11,13,15,17,19-nonaen-4-yl]propanoic acidsirohydrochlorin65207-12-7C[C@]1(CC(O)=O)[C@H](CCC(O)=O)\C2=C\C3=N\C(=C/C4=C(CCC(O)=O)C(CC(O)=O)=C(N4)\C=C4/N=C(/C=C1\N2)[C@@H](CCC(O)=O)[C@]4(C)CC(O)=O)\C(CCC(O)=O)=C3CC(O)=OInChI=1S/C42H46N4O16/c1-41(17-39(59)60)23(5-9-35(51)52)29-14-27-21(11-37(55)56)19(3-7-33(47)48)25(43-27)13-26-20(4-8-34(49)50)22(12-38(57)58)28(44-26)15-31-42(2,18-40(61)62)24(6-10-36(53)54)30(46-31)16-32(41)45-29/h13-16,23-24,44-45H,3-12,17-18H2,1-2H3,(H,47,48)(H,49,50)(H,51,52)(H,53,54)(H,55,56)(H,57,58)(H,59,60)(H,61,62)/b25-13-,29-14-,31-15-,32-16-/t23-,24-,41+,42+/m1/s1KWIZRXMMFRBUML-AHGFGAHVSA-NCytosolMembranelogp1.04logs-4.54solubility2.52e-02 g/llogp3.12pka_strongest_acidic3.06iupac3-[(4S,5S,9S,10S)-9,15,19-tris(2-carboxyethyl)-5,10,14,20-tetrakis(carboxymethyl)-5,10-dimethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1(21),2,6,8(23),11,13,15,17,19-nonaen-4-yl]propanoic acidaverage_mass862.8318mono_mass862.290881444smilesC[C@]1(CC(O)=O)[C@H](CCC(O)=O)\C2=C\C3=N\C(=C/C4=C(CCC(O)=O)C(CC(O)=O)=C(N4)\C=C4/N=C(/C=C1\N2)[C@@H](CCC(O)=O)[C@]4(C)CC(O)=O)\C(CCC(O)=O)=C3CC(O)=OformulaC42H46N4O16inchiInChI=1S/C42H46N4O16/c1-41(17-39(59)60)23(5-9-35(51)52)29-14-27-21(11-37(55)56)19(3-7-33(47)48)25(43-27)13-26-20(4-8-34(49)50)22(12-38(57)58)28(44-26)15-31-42(2,18-40(61)62)24(6-10-36(53)54)30(46-31)16-32(41)45-29/h13-16,23-24,44-45H,3-12,17-18H2,1-2H3,(H,47,48)(H,49,50)(H,51,52)(H,53,54)(H,55,56)(H,57,58)(H,59,60)(H,61,62)/b25-13-,29-14-,31-15-,32-16-/t23-,24-,41+,42+/m1/s1inchikeyKWIZRXMMFRBUML-AHGFGAHVSA-Npolar_surface_area355.76refractivity209.38polarizability89.44rotatable_bond_count20acceptor_count18donor_count10physiological_charge-8formal_charge0Porphyrin and chlorophyll metabolismec00860Porphyrin 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.
PW000936Metabolicsiroheme biosynthesisPWY-5194Specdb::NmrOneD298705Specdb::NmrOneD298706Specdb::NmrOneD298707Specdb::NmrOneD298708Specdb::NmrOneD298709Specdb::NmrOneD298710Specdb::NmrOneD298711Specdb::NmrOneD298712Specdb::NmrOneD298713Specdb::NmrOneD298714Specdb::NmrOneD298715Specdb::NmrOneD298716Specdb::NmrOneD298717Specdb::NmrOneD298718Specdb::NmrOneD298719Specdb::NmrOneD298720Specdb::NmrOneD298721Specdb::NmrOneD298722Specdb::NmrOneD298723Specdb::NmrOneD298724Specdb::MsMs179124Specdb::MsMs179125Specdb::MsMs179126Specdb::MsMs181449Specdb::MsMs181450Specdb::MsMs181451196427C0577818023SIROHYDROCHLORINKeseler, 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 80:2939-2948.18331064Fazzio, T. G., Roth, J. R. (1996). "Evidence that the CysG protein catalyzes the first reaction specific to B12 synthesis in Salmonella typhimurium, insertion of cobalt." J Bacteriol 178:6952-6959.8955319Siroheme synthaseP0AEA8CYSG_ECOLIcysGhttp://ecmdb.ca/proteins/P0AEA8.xmlIron + Sirohydrochlorin >3 Hydrogen ion + SirohemeSIROHEME-FERROCHELAT-RXNPrecorrin 2 + NAD > Hydrogen ion + NADH + SirohydrochlorinR03947DIMETHUROPORDEHYDROG-RXNSiroheme + 2 Hydrogen ion <> Fe2+ + SirohydrochlorinR02864Precorrin 2 + NAD <> Sirohydrochlorin + NADH + Hydrogen ionR03947Sirohydrochlorin + Iron <> Hydrogen ion + SirohemeSIROHEME-FERROCHELAT-RXNPrecorrin-2 + NAD > Sirohydrochlorin + NADHSiroheme + 2 Hydrogen ion > Sirohydrochlorin + IronPrecorrin-2 + NAD > NADH + Hydrogen ion + SirohydrochlorinPW_R003491Sirohydrochlorin + Iron >2 Hydrogen ion + SirohemePW_R003492Precorrin 2 + NAD <> Sirohydrochlorin + NADH +2 Hydrogen ionPW_R005872