2.02012-05-31 09:57:42 -06002015-09-13 12:56:06 -0600ECMDB00121M2MDB000044Folic acidFolic acid is a member of the vitamin B family. Folic acid, being biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are transported across cells by receptor-mediated endocytosis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylated tRNA, and generate and use formate.AcifolicCytofolDosfolat B activFolacidFolacinFolateFolbalFolcidinFoldineFolettesFoliaminFolic acidFolicetFolipacFolsanFolsaureFolsavFolviteIncafolicLiver Lactobacillus casei factorMillafolN-(4-{[(2-Amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamateN-(4-{[(2-Amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acidN-Pteroyl-L-glutamateN-Pteroyl-L-glutamic acidN-[(4-{[(2-Amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)carbonyl]-L-glutamateN-[(4-{[(2-Amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)carbonyl]-L-glutamic acidN-[4-[[(2-Amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamateN-[4-[[(2-Amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acidPGAPteGluPteroyl-L-glutamatePteroyl-L-glutamic acidPteroyl-L-monoglutamatePteroyl-L-monoglutamic acidPteroylglutamatePteroylglutamic acidPteroylmonoglutamatePteroylmonoglutamic acidVitamin BcVitamin BeVitamin MC19H19N7O6441.3975441.139681375(2S)-2-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acidfolate59-30-3NC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1InChI=1S/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1OVBPIULPVIDEAO-LBPRGKRZSA-NSolidCytoplasmPeriplasmlogp-0.04logs-3.76solubility7.61e-02 g/lmelting_point250 oClogp-0.68pka_strongest_acidic3.37pka_strongest_basic2.09iupac(2S)-2-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acidaverage_mass441.3975mono_mass441.139681375smilesNC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1formulaC19H19N7O6inchiInChI=1S/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1inchikeyOVBPIULPVIDEAO-LBPRGKRZSA-Npolar_surface_area208.99refractivity111.01polarizability42.06rotatable_bond_count9acceptor_count12donor_count6physiological_charge-2formal_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.
PW000908ec00790MetabolicOne carbon pool by folateDihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes.
Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid.
Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase.
Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF
Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions.
Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF
Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF.
The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes:
1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate
2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate
3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate
4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate
10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and
5,10-methenyltetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a
5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF.
PW000773ec00670MetabolicOne Carbon Pool by Folate IDihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes.
Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid.
Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase.
Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF
Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions.
Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF
Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF.
The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes:
1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate
2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate
3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate
4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate
10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and
5,10-methenyltetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a
5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF.
PW001735MetabolicSpecdb::CMs22269Specdb::CMs37303Specdb::CMs165078Specdb::CMs1050360Specdb::CMs1050362Specdb::CMs1050364Specdb::CMs1050366Specdb::CMs1050367Specdb::CMs1050369Specdb::CMs1050371Specdb::CMs1050373Specdb::CMs1050375Specdb::CMs1050377Specdb::CMs1050379Specdb::CMs1050381Specdb::CMs1050382Specdb::CMs1050384Specdb::CMs1050386Specdb::CMs1050388Specdb::CMs1050390Specdb::CMs1050392Specdb::CMs1050394Specdb::CMs1050395Specdb::CMs1050397Specdb::CMs1050399Specdb::EiMs344Specdb::NmrOneD1092Specdb::NmrOneD2513Specdb::NmrOneD3211Specdb::NmrOneD5134Specdb::NmrOneD5135Specdb::NmrOneD5772Specdb::NmrOneD5773Specdb::NmrOneD5774Specdb::NmrOneD5775Specdb::NmrOneD5776Specdb::NmrOneD5777Specdb::NmrOneD5778Specdb::NmrOneD5779Specdb::NmrOneD5780Specdb::NmrOneD5781Specdb::NmrOneD5782Specdb::NmrOneD5783Specdb::NmrOneD5784Specdb::NmrOneD5785Specdb::NmrOneD5786Specdb::NmrOneD5787Specdb::NmrOneD5788Specdb::NmrOneD5789Specdb::NmrOneD5790Specdb::NmrOneD5791Specdb::MsMs174Specdb::MsMs175Specdb::MsMs176Specdb::MsMs2912Specdb::MsMs182913Specdb::MsMs182914Specdb::MsMs182915Specdb::MsMs183261Specdb::MsMs183262Specdb::MsMs183263Specdb::MsMs374579Specdb::MsMs439273Specdb::MsMs451198Specdb::MsMs2226655Specdb::MsMs2226878Specdb::MsMs2227812Specdb::MsMs2228083Specdb::MsMs2229178Specdb::MsMs2229235Specdb::MsMs2230246Specdb::MsMs2230263Specdb::MsMs2231457Specdb::MsMs2231502Specdb::MsMs2231600Specdb::MsMs2232575Specdb::NmrTwoD1150HMDB0012160375815C0050427470CPD-12826FOLFolic acidKeseler, I. 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Journal of Heterocyclic Chemistry (1987), 24(1), 279-82.http://hmdb.ca/system/metabolites/msds/000/000/082/original/HMDB00121.pdf?1358894364Dihydrofolate reductaseP0ABQ4DYR_ECOLIfolAhttp://ecmdb.ca/proteins/P0ABQ4.xmlTetrahydrofolic acid + 2 NAD <> Folic acid +2 NADH +2 Hydrogen ionR00937Tetrahydrofolic acid + 2 NADP <> Folic acid +2 NADPH +2 Hydrogen ionR00940Dihydrofolic acid + NAD <> Folic acid + NADH + Hydrogen ionR02235Dihydrofolic acid + NADP <> Folic acid + NADPH + Hydrogen ionR02236Dihydrofolic acid + NADP + Dihydrofolic acid > Folic acid + NADPH + Hydrogen ion + NADPHPW_R002537Folic acid + 2 NADPH + 2 Hydrogen ion + 2 NADPH > Tetrahydrofolic acid +2 NADP + Tetrahydrofolic acidPW_R004674