2.0 2012-05-31 13:54:35 -0600 2015-06-03 15:54:12 -0600 ECMDB01562 M2MDB000421 N5-Formyl-H4F N5-Formyl-H4F is the active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. (6R,S)-5-Formyltetrahydrofolate (6R,S)-5-Formyltetrahydrofolic acid 10-Formyl-7,8-dihydrofolate 10-Formyl-7,8-dihydrofolic acid 5-CHO-THF 5-Formyl-5,6,7,8-tetrahydrofolate 5-Formyl-5,6,7,8-tetrahydrofolic acid 5-formyl-H4F 5-Formyl-THF 5-Formyl-THF leucovorin 5-Formyltetrahydrofolate 5-Formyltetrahydrofolic acid 5-Formyltetrahydropteroylglutamate 5-Formyltetrahydropteroylglutamic acid Citrovorum factor Folinate Folinate-SF Folinic acid Folinic acid-SF Formyl-H4F L-Leucovorin L-N-[p-[[(2-Amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-Glutamate L-N-[p-[[(2-Amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-Glutamic acid Leucal Levoleucovorin N5-Formyl-5,6,7,8-tetrahydrofolate N5-Formyl-5,6,7,8-tetrahydrofolic acid N5-formyl-thf N5-Formyltetrahydrofolate N5-Formyltetrahydrofolic acid N⁵-formyl-H4F N⁵-formyl-THF Welcovorin C20H23N7O7 473.4393 473.165896125 2-[(4-{[(2-amino-5-formyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid 2-[(4-{[(2-amino-5-formyl-4-oxo-3,6,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid 58-05-9 NC1=NC2=C(N(C=O)C(CNC3=CC=C(C=C3)C(=O)NC(CCC(O)=O)C(O)=O)CN2)C(=O)N1 InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32) VVIAGPKUTFNRDU-UHFFFAOYSA-N Solid Cytosol logp -1.56 ALOGPS logs -3.43 ALOGPS solubility 1.76e-01 g/l ALOGPS logp -2.3 ChemAxon pka_strongest_acidic 3.47 ChemAxon pka_strongest_basic 2.81 ChemAxon iupac 2-[(4-{[(2-amino-5-formyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid ChemAxon average_mass 473.4393 ChemAxon mono_mass 473.165896125 ChemAxon smiles NC1=NC2=C(N(C=O)C(CNC3=CC=C(C=C3)C(=O)NC(CCC(O)=O)C(O)=O)CN2)C(=O)N1 ChemAxon formula C20H23N7O7 ChemAxon inchi InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32) ChemAxon inchikey VVIAGPKUTFNRDU-UHFFFAOYSA-N ChemAxon polar_surface_area 215.55 ChemAxon refractivity 126.66 ChemAxon polarizability 46.54 ChemAxon rotatable_bond_count 9 ChemAxon acceptor_count 11 ChemAxon donor_count 7 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon One carbon pool by folate Dihydrofolic 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. PW000773 ec00670 Metabolic Metabolic pathways eco01100 One Carbon Pool by Folate I Dihydrofolic 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. PW001735 Metabolic Specdb::CMs 25520 Specdb::CMs 38127 Specdb::CMs 117810 Specdb::CMs 127258 Specdb::CMs 128849 Specdb::CMs 829601 Specdb::CMs 829602 Specdb::CMs 829603 Specdb::CMs 829604 Specdb::CMs 829605 Specdb::CMs 829606 Specdb::CMs 829607 Specdb::CMs 829608 Specdb::CMs 829609 Specdb::CMs 829610 Specdb::CMs 829611 Specdb::CMs 829612 Specdb::CMs 829613 Specdb::CMs 829614 Specdb::CMs 829615 Specdb::CMs 829616 Specdb::CMs 829617 Specdb::CMs 829618 Specdb::CMs 829619 Specdb::CMs 829620 Specdb::NmrOneD 201667 Specdb::NmrOneD 201668 Specdb::NmrOneD 201669 Specdb::NmrOneD 201670 Specdb::NmrOneD 201671 Specdb::NmrOneD 201672 Specdb::NmrOneD 201673 Specdb::NmrOneD 201674 Specdb::NmrOneD 201675 Specdb::NmrOneD 201676 Specdb::NmrOneD 201677 Specdb::NmrOneD 201678 Specdb::NmrOneD 201679 Specdb::NmrOneD 201680 Specdb::NmrOneD 201681 Specdb::NmrOneD 201682 Specdb::NmrOneD 201683 Specdb::NmrOneD 201684 Specdb::NmrOneD 201685 Specdb::NmrOneD 201686 Specdb::MsMs 26219 Specdb::MsMs 26220 Specdb::MsMs 26221 Specdb::MsMs 32777 Specdb::MsMs 32778 Specdb::MsMs 32779 Specdb::MsMs 3409760 Specdb::MsMs 3409761 Specdb::MsMs 3409762 Specdb::MsMs 3409763 Specdb::MsMs 3409764 Specdb::MsMs 3409765 HMDB01562 143 140 C03479 5-FORMYL-THF folinate 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 Perry TL, Applegarth DA, Evans ME, Hansen S, Jellum E: Metabolic studies of a family with massive formiminoglutamic aciduria. Pediatr Res. 1975 Mar;9(3):117-22. 235753 Garbis SD, Melse-Boonstra A, West CE, van Breemen RB: Determination of folates in human plasma using hydrophilic interaction chromatography-tandem mass spectrometry. 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Serine hydroxymethyltransferase P0A825 GLYA_ECOLI glyA http://ecmdb.ca/proteins/P0A825.xml Aminomethyltransferase P27248 GCST_ECOLI gcvT http://ecmdb.ca/proteins/P27248.xml Uncharacterized protein ygfA P0AC28 YGFA_ECOLI ygfA http://ecmdb.ca/proteins/P0AC28.xml Water + 5,10-Methenyltetrahydrofolate > N5-Formyl-H4F + Hydrogen ion N5-Formyl-H4F + Hydrogen ion > Water + 5,10-Methenyltetrahydrofolate R02300 RXN-6321 N5-Formyl-H4F <> 5,10-Methenyltetrahydrofolate + Water R02300 5,10-Methenyltetrahydrofolate + Water Hydrogen ion + N5-Formyl-H4F RXN-6321 N5-Formyl-H4F + Adenosine triphosphate > 5,10-Methenyltetrahydrofolate + ADP + Phosphate 5-FORMYL-THF-CYCLO-LIGASE-RXN Adenosine triphosphate + N5-Formyl-H4F <> ADP + Phosphate + 5,10-Methenyltetrahydrofolate R02301 Water + 5,10-Methenyltetrahydrofolic acid > N5-Formyl-THF + N5-Formyl-H4F PW_R002552 N5-Formyl-H4F + Hydrogen ion > Water +5 5,10-Methenyltetrahydrofolate N5-Formyl-H4F + Hydrogen ion > Water +5 5,10-Methenyltetrahydrofolate