2.02012-05-31 13:52:03 -06002015-06-03 15:54:05 -0600ECMDB01412M2MDB0003767,8-Dihydropteroic acid7,8-dihydropteroate is an intermediate product in dihydrofolate synthesis. It occurs via the enzymic catalysis of the reaction of 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine pyrophosphate with p-aminobenzoate. The enzymes 6-hydroxymethylpterin pyrophosphokinase (EC 2.7.6.3, HPPK) and dihydropteroate synthase (EC 2.5.1.15, DHPS) catalyze sequential steps in folate biosynthesis. 4-[[(2-Amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoate4-[[(2-Amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoic acid4-[[(2-Amino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoate4-[[(2-Amino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoic acid7,8-Dihydropteroate7,8-Dihydropteroic acidDHPADihydropterateDihydropteric acidDihydropteroateDihydropteroic acidH2PteP-[[(2-Amino-7,8-dihydro-4-hydroxy-6-pteridinyl)methyl]amino]-BenzoateP-[[(2-Amino-7,8-dihydro-4-hydroxy-6-pteridinyl)methyl]amino]-Benzoic acidC14H14N6O3314.2994314.1127383444-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoic acid7,8-dihydropteroic acid2134-76-1NC1=NC2=C(N=C(CNC3=CC=C(C=C3)C(O)=O)CN2)C(=O)N1InChI=1S/C14H14N6O3/c15-14-19-11-10(12(21)20-14)18-9(6-17-11)5-16-8-3-1-7(2-4-8)13(22)23/h1-4,16H,5-6H2,(H,22,23)(H4,15,17,19,20,21)WBFYVDCHGVNRBH-UHFFFAOYSA-NSolidCytosollogp-0.21logs-3.36solubility1.37e-01 g/llogp-0.26pka_strongest_acidic4.72pka_strongest_basic1.76iupac4-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoic acidaverage_mass314.2994mono_mass314.112738344smilesNC1=NC2=C(N=C(CNC3=CC=C(C=C3)C(O)=O)CN2)C(=O)N1formulaC14H14N6O3inchiInChI=1S/C14H14N6O3/c15-14-19-11-10(12(21)20-14)18-9(6-17-11)5-16-8-3-1-7(2-4-8)13(22)23/h1-4,16H,5-6H2,(H,22,23)(H4,15,17,19,20,21)inchikeyWBFYVDCHGVNRBH-UHFFFAOYSA-Npolar_surface_area141.2refractivity93.1polarizability31.6rotatable_bond_count4acceptor_count8donor_count5physiological_charge-1formal_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 pathwayseco01100formylTHF biosynthesis I1CMET2-PWYtetrahydrofolate biosynthesisPWY-6614Specdb::CMs26375Specdb::CMs38061Specdb::CMs166850Specdb::NmrOneD96018Specdb::NmrOneD96019Specdb::NmrOneD96020Specdb::NmrOneD96021Specdb::NmrOneD96022Specdb::NmrOneD96023Specdb::NmrOneD96024Specdb::NmrOneD96025Specdb::NmrOneD96026Specdb::NmrOneD96027Specdb::NmrOneD96028Specdb::NmrOneD96029Specdb::NmrOneD96030Specdb::NmrOneD96031Specdb::NmrOneD96032Specdb::NmrOneD96033Specdb::NmrOneD96034Specdb::NmrOneD96035Specdb::NmrOneD96036Specdb::NmrOneD96037Specdb::MsMs25730Specdb::MsMs25731Specdb::MsMs25732Specdb::MsMs32288Specdb::MsMs32289Specdb::MsMs32290Specdb::MsMs2331551Specdb::MsMs2331552Specdb::MsMs2331553Specdb::MsMs2630168Specdb::MsMs2630169Specdb::MsMs2630170HMDB01412170165C0092145817-8-DIHYDROPTEROATE78HDihydropteroateKeseler, 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 80:2939-2948.18331064Bartels, Rainer; Bock, Lothar. Determination of pteroic acid by high-performance thin-layer chromatography. Contribution to the investigation of 7,8-dihydropteroate synthase. Journal of Chromatography (1994), 659(1), 185-9.Bifunctional protein folCP08192FOLC_ECOLIfolChttp://ecmdb.ca/proteins/P08192.xmlDihydropteroate synthaseP0AC13DHPS_ECOLIfolPhttp://ecmdb.ca/proteins/P0AC13.xmlAdenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Dihydrofolic acid + Hydrogen ion + PhosphateR02237DIHYDROFOLATESYNTH-RXNp-Aminobenzoic acid + 6-Hydroxymethyl-dihydropterin pyrophosphate > 7,8-Dihydropteroic acid + PyrophosphateH2PTEROATESYNTH-RXNAdenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Phosphate + Dihydrofolic acidR022376-Hydroxymethyl dihydropterin + p-Aminobenzoic acid <> 7,8-Dihydropteroic acid + WaterR030662-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate + p-Aminobenzoic acid + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate <> Pyrophosphate + 7,8-Dihydropteroic acidR03067L-Glutamate + 7,8-Dihydropteroic acid + Adenosine triphosphate > Hydrogen ion + Dihydrofolic acid + Phosphate + ADPDIHYDROFOLATESYNTH-RXN2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate + p-Aminobenzoic acid > Pyrophosphate + 7,8-Dihydropteroic acidAdenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate > ADP + Inorganic phosphate + Dihydrofolic acid6-Hydroxymethyl-dihydropterin pyrophosphate + p-Aminobenzoic acid > Pyrophosphate + 7,8-Dihydropteroic acidPW_R0034017,8-Dihydropteroic acid + Adenosine triphosphate + L-Glutamic acid + L-Glutamate > Adenosine diphosphate + Phosphate + Hydrogen ion + 7,8-dihydrofolate monoglutamate + ADP + Dihydrofolic acidPW_R003404Adenosine triphosphate + 7 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Dihydrofolic acid + Hydrogen ion + Phosphate6 6-Hydroxymethyl dihydropterin + p-Aminobenzoic acid <>7 7,8-Dihydropteroic acid + Water6 6-Hydroxymethyl dihydropterin + p-Aminobenzoic acid <>7 7,8-Dihydropteroic acid + Water