2.0 2012-05-31 13:52:03 -0600 2015-06-03 15:54:05 -0600 ECMDB01412 M2MDB000376 7,8-Dihydropteroic acid 7,8-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]-Benzoate 4-[[(2-Amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoic acid 4-[[(2-Amino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoate 4-[[(2-Amino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoic acid 7,8-Dihydropteroate 7,8-Dihydropteroic acid DHPA Dihydropterate Dihydropteric acid Dihydropteroate Dihydropteroic acid H2Pte P-[[(2-Amino-7,8-dihydro-4-hydroxy-6-pteridinyl)methyl]amino]-Benzoate P-[[(2-Amino-7,8-dihydro-4-hydroxy-6-pteridinyl)methyl]amino]-Benzoic acid C14H14N6O3 314.2994 314.112738344 4-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoic acid 7,8-dihydropteroic acid 2134-76-1 NC1=NC2=C(N=C(CNC3=CC=C(C=C3)C(O)=O)CN2)C(=O)N1 InChI=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-N Solid Cytosol logp -0.21 ALOGPS logs -3.36 ALOGPS solubility 1.37e-01 g/l ALOGPS logp -0.26 ChemAxon pka_strongest_acidic 4.72 ChemAxon pka_strongest_basic 1.76 ChemAxon iupac 4-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoic acid ChemAxon average_mass 314.2994 ChemAxon mono_mass 314.112738344 ChemAxon smiles NC1=NC2=C(N=C(CNC3=CC=C(C=C3)C(O)=O)CN2)C(=O)N1 ChemAxon formula C14H14N6O3 ChemAxon inchi InChI=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) ChemAxon inchikey WBFYVDCHGVNRBH-UHFFFAOYSA-N ChemAxon polar_surface_area 141.2 ChemAxon refractivity 93.1 ChemAxon polarizability 31.6 ChemAxon rotatable_bond_count 4 ChemAxon acceptor_count 8 ChemAxon donor_count 5 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Folate biosynthesis The 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. PW000908 ec00790 Metabolic Metabolic pathways eco01100 formylTHF biosynthesis I 1CMET2-PWY tetrahydrofolate biosynthesis PWY-6614 Specdb::CMs 26375 Specdb::CMs 38061 Specdb::CMs 166850 Specdb::NmrOneD 96018 Specdb::NmrOneD 96019 Specdb::NmrOneD 96020 Specdb::NmrOneD 96021 Specdb::NmrOneD 96022 Specdb::NmrOneD 96023 Specdb::NmrOneD 96024 Specdb::NmrOneD 96025 Specdb::NmrOneD 96026 Specdb::NmrOneD 96027 Specdb::NmrOneD 96028 Specdb::NmrOneD 96029 Specdb::NmrOneD 96030 Specdb::NmrOneD 96031 Specdb::NmrOneD 96032 Specdb::NmrOneD 96033 Specdb::NmrOneD 96034 Specdb::NmrOneD 96035 Specdb::NmrOneD 96036 Specdb::NmrOneD 96037 Specdb::MsMs 25730 Specdb::MsMs 25731 Specdb::MsMs 25732 Specdb::MsMs 32288 Specdb::MsMs 32289 Specdb::MsMs 32290 Specdb::MsMs 2331551 Specdb::MsMs 2331552 Specdb::MsMs 2331553 Specdb::MsMs 2630168 Specdb::MsMs 2630169 Specdb::MsMs 2630170 HMDB01412 170 165 C00921 4581 7-8-DIHYDROPTEROATE 78H Dihydropteroate 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 Bartels, 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 folC P08192 FOLC_ECOLI folC http://ecmdb.ca/proteins/P08192.xml Dihydropteroate synthase P0AC13 DHPS_ECOLI folP http://ecmdb.ca/proteins/P0AC13.xml Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Dihydrofolic acid + Hydrogen ion + Phosphate R02237 DIHYDROFOLATESYNTH-RXN p-Aminobenzoic acid + 6-Hydroxymethyl-dihydropterin pyrophosphate > 7,8-Dihydropteroic acid + Pyrophosphate H2PTEROATESYNTH-RXN Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Phosphate + Dihydrofolic acid R02237 6-Hydroxymethyl dihydropterin + p-Aminobenzoic acid <> 7,8-Dihydropteroic acid + Water R03066 2-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 acid R03067 L-Glutamate + 7,8-Dihydropteroic acid + Adenosine triphosphate > Hydrogen ion + Dihydrofolic acid + Phosphate + ADP DIHYDROFOLATESYNTH-RXN 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate + p-Aminobenzoic acid > Pyrophosphate + 7,8-Dihydropteroic acid Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate > ADP + Inorganic phosphate + Dihydrofolic acid 6-Hydroxymethyl-dihydropterin pyrophosphate + p-Aminobenzoic acid > Pyrophosphate + 7,8-Dihydropteroic acid PW_R003401 7,8-Dihydropteroic acid + Adenosine triphosphate + L-Glutamic acid + L-Glutamate > Adenosine diphosphate + Phosphate + Hydrogen ion + 7,8-dihydrofolate monoglutamate + ADP + Dihydrofolic acid PW_R003404 Adenosine triphosphate + 7 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Dihydrofolic acid + Hydrogen ion + Phosphate 6 6-Hydroxymethyl dihydropterin + p-Aminobenzoic acid <>7 7,8-Dihydropteroic acid + Water 6 6-Hydroxymethyl dihydropterin + p-Aminobenzoic acid <>7 7,8-Dihydropteroic acid + Water