2.02012-05-31 14:52:51 -06002015-06-03 17:20:22 -0600ECMDB20601M2MDB001401Cyclic pyranopterin monophosphateCyclic pyranopterin monophosphate is a member of the chemical class known as Pterins and Derivatives. These are polycyclic aromatic compounds containing a pterin moeity, which consist of a pteridine ring bearing a ketone and an amine group to form 2-aminopteridin-4(3H)-one. cPMP is a precursor to molybdenum cofactor, which is required for the enyzme activity of sulfite oxidase, xanthine dehydrogenase/oxidase and aldehyde oxidase. The transition element molybdenum (Mo) has been long known as an essential micronutrient across the kingdoms of plants, animals, fungi and bacteria. However, molybdate itself is catalytically inactive and, with the exception of bacterial nitrogenase, needs to be activated through complexation by a special cofactor. There are several molybdenum cofactors, including molybdopterin (MPT), guanylyl molybdenum cofactor (MGD), cytidylyl molybdenum cofactor, or others. In Escherichia coli, the MoaD protein plays a central role in the conversion of precursor Z to molybdopterin (MPT) during molybdenum cofactor biosynthesis. (PMID 17223713) In Escherichia coli, MPT is formed by incorporation of two sulfur atoms into precursor Z, which is catalyzed by MPT synthase. (PMID 11459846)8-Amino-2,12,12-trihydroxy-4,4a,5a,6,9,10,11,11a,12,12a-decahydro-[1,3,2]dioxaphosphinino[4',5':5,6]pyrano[3,2-g]pteridine 2-oxide8-Amino-2,12,12-trihydroxy-4a,5a,6,9,11,11a,12,12a-octahydro[1,3,2]dioxaphosphinino[4',5':5,6]pyrano[3,2-g]pteridin-10(4H)-one 2-oxideCPMPCyclic pyranopterin monophosphateCyclic pyranopterin monophosphoric acidPrecursor zPrecursor-ZC10H14N5O8P363.2206363.057998961(4aR,5aR,11aR,12aS)-2,10,12,12-tetrahydroxy-8-imino-4,4a,5a,6,7,8,11,11a,12,12a-decahydro-2H-1,3,5-trioxa-6,7,9,11-tetraaza-2lambda5-phosphatetracen-2-one(4aR,5aR,11aR,12aS)-2,10,12,12-tetrahydroxy-8-imino-4,4a,5a,6,7,11,11a,12a-octahydro-1,3,5-trioxa-6,7,9,11-tetraaza-2lambda5-phosphatetracen-2-one[H][C@@]12COP(O)(=O)O[C@]1([H])C(O)(O)[C@]1([H])NC3=C(NC(=N)N=C3O)N[C@]1([H])O2InChI=1S/C10H14N5O8P/c11-9-14-6-3(7(16)15-9)12-4-8(13-6)22-2-1-21-24(19,20)23-5(2)10(4,17)18/h2,4-5,8,12,17-18H,1H2,(H,19,20)(H4,11,13,14,15,16)/t2-,4-,5+,8-/m1/s1CZAKJJUNKNPTTO-AJFJRRQVSA-NCytosollogp-1.97logs-1.60solubility9.05e+00 g/llogp-3.2pka_strongest_acidic1.8pka_strongest_basic3.96iupac(4aR,5aR,11aR,12aS)-2,10,12,12-tetrahydroxy-8-imino-4,4a,5a,6,7,8,11,11a,12,12a-decahydro-2H-1,3,5-trioxa-6,7,9,11-tetraaza-2lambda5-phosphatetracen-2-oneaverage_mass363.2206mono_mass363.057998961smiles[H][C@@]12COP(O)(=O)O[C@]1([H])C(O)(O)[C@]1([H])NC3=C(NC(=N)N=C3O)N[C@]1([H])O2formulaC10H14N5O8PinchiInChI=1S/C10H14N5O8P/c11-9-14-6-3(7(16)15-9)12-4-8(13-6)22-2-1-21-24(19,20)23-5(2)10(4,17)18/h2,4-5,8,12,17-18H,1H2,(H,19,20)(H4,11,13,14,15,16)/t2-,4-,5+,8-/m1/s1inchikeyCZAKJJUNKNPTTO-AJFJRRQVSA-Npolar_surface_area197.98refractivity93.04polarizability29.91rotatable_bond_count0acceptor_count11donor_count8physiological_charge0formal_charge0Folate biosynthesisThe biosynthesis of folic acid begins with a product of purine nucleotides de novo biosynthesis pathway, GTP. This compound is involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphatased through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter compound reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. This compound reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. The latter compound is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate.
Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter compound then reacts through an aminodeoxychorismate lyase resulting in pyruvic acid,hydrogen ion and p-aminobenzoic acid.
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react through a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthetase / dihydrofolate synthetase resulting in a 7,8-dihydrofolate monoglutamate. This compound is reduced through an NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate.
This product goes on to a one carbon pool by folate pathway.
PW000908ec00790MetabolicMetabolic pathwayseco01100GTP degradationGTP, produced in the nucleotide de novo biosyntheis pathway, interacts with a water molecule through a GTP cyclohydrolase resulting in a formate, hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound interacts with a water molecule through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, a hydrogen ion and a 7,8-dihydroneopterin 3'-phosphate. The latter compound interacts with water spontaneously resulting in the release of a phosphate and a 7,8 dihydroneopterin. The latter compound interacts with a dihydroneopterin aldolase resulting in the release of a glycolaldehyde and a 6-hydroxymethyl-7,8-dihydropterin. This compound then is then diphosphorylated by reacting with a ATP driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in the release of a hydrogen ion, an AMP and 6-hydroxymethyl-7,8-dihydropterin diphosphate.
GTP interacts with a cyclic pyranopterin monophosphate synthase resulting in the release of a diphosphate and a cyclic pyranopterin phosphate. The latter compound interacts with a thiocarboxylated small subunit of molybdopterin synthase (a protein) and a water molecule through a molybdopterin synthase resulting in the release of 4 hydrogen ions, 2 small subunits of molybdopterin synthase and a molybdopterin. The molybdopterin interacts with an ATP and a hydrogen ion through a molybdopterin adenylyltransferase resulting in the release of a diphosphate and a molybdopterin adenine dinucleotide.PW001888Metabolicmolybdenum cofactor biosynthesisPWY-6823Specdb::CMs34723Specdb::CMs47831Specdb::CMs133650Specdb::CMs141384Specdb::NmrOneD51742Specdb::NmrOneD51743Specdb::NmrOneD51744Specdb::NmrOneD51745Specdb::NmrOneD51746Specdb::NmrOneD51747Specdb::NmrOneD51748Specdb::NmrOneD51749Specdb::NmrOneD51750Specdb::NmrOneD51751Specdb::NmrOneD51752Specdb::NmrOneD51753Specdb::NmrOneD51754Specdb::NmrOneD51755Specdb::NmrOneD51756Specdb::NmrOneD51757Specdb::NmrOneD51758Specdb::NmrOneD51759Specdb::NmrOneD51760Specdb::NmrOneD51761Specdb::MsMs28154Specdb::MsMs28155Specdb::MsMs28156Specdb::MsMs34712Specdb::MsMs34713Specdb::MsMs34714Specdb::MsMs2452708Specdb::MsMs2452709Specdb::MsMs2452710Specdb::MsMs2482123Specdb::MsMs2482124Specdb::MsMs248212525202908C18239PRECURSOR-ZKeseler, 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-D114.22080510Winder, 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 80:2939-2948.18331064Gutzke, G., Fischer, B., Mendel, R. R., Schwarz, G. (2001). "Thiocarboxylation of molybdopterin synthase provides evidence for the mechanism of dithiolene formation in metal-binding pterins." J Biol Chem 276:36268-36274.11459846Molybdopterin synthase sulfur carrier subunitP30748MOAD_ECOLImoaDhttp://ecmdb.ca/proteins/P30748.xmlMolybdopterin synthase catalytic subunitP30749MOAE_ECOLImoaEhttp://ecmdb.ca/proteins/P30749.xmlMolybdenum cofactor biosynthesis protein AP30745MOAA_ECOLImoaAhttp://ecmdb.ca/proteins/P30745.xmlMolybdenum cofactor biosynthesis protein CP0A738MOAC_ECOLImoaChttp://ecmdb.ca/proteins/P0A738.xmlGuanosine triphosphate + Water <> Cyclic pyranopterin monophosphate + PyrophosphateR09394Cyclic pyranopterin monophosphate + Copper + 2 MoaD Protein with thiocarboxylate >5 Hydrogen ion +2 MoaD Protein with carboxylate + MolybdopterinCyclic pyranopterin monophosphate + 2 Sulfur donor <> MolybdopterinR09395Guanosine triphosphate > Cyclic pyranopterin monophosphate + PyrophosphateRXN-8340Cyclic pyranopterin monophosphate + Water + Thiocarboxylated-MPT-synthases > Molybdopterin + MPT-SynthasesRXN-8342Cyclic pyranopterin monophosphate + 2 [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH(2)-C(O)SH + Water > molybdopterin forma +2 [molybdopterin-synthase sulfur-carrier protein]Guanosine triphosphate > Cyclic pyranopterin monophosphate + PyrophosphatePW_R005152Cyclic pyranopterin monophosphate + Water + thiocarboxylated small subunit of molybdopterin synthase >4 Hydrogen ion +2 thiocarboxylated small subunit of molybdopterin synthase + Molybdopterin + MolybdopterinPW_R005153Cyclic pyranopterin monophosphate + 2 Sulfur donor <> MolybdopterinGuanosine triphosphate + Water <> Cyclic pyranopterin monophosphate + PyrophosphateCyclic pyranopterin monophosphate + 2 Sulfur donor <> Molybdopterin