2.0 2012-05-31 13:51:35 -0600 2015-09-17 15:41:11 -0600 ECMDB01396 M2MDB000368 5-Methyltetrahydrofolic acid 5 methyltetrahydrofolic acid (5-MTHF) is the most biologically active form of the B-vitamin folic acid, also known generically as folate. It is a methylated derivate of tetrahydrofolate (THF, H4F). It is generated by methylenetetrahydrofolate reductase (MTHFR) from 5,10-methylenetetrahydrofolate (5,10-CH2-THF, MTHF) and used to recycle homocysteine back to methionine by 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) or methionine synthase (MS). 5-MTHF functions, in concert with vitamin B12, as a methyl-group donor involved in the conversion of the amino acid homocysteine to methionine. Methyl (CH3) group donation is vital to many cellular processes. 5-Methyl tetrahydrofolate 5-Methyl tetrahydrofolic acid 5-Methyl-5,6,7,8-tetrahydrofolate 5-Methyl-5,6,7,8-tetrahydrofolic acid 5-Methyl-5,6,7,8-tetrahydropteroyl-L-glutamate 5-Methyl-5,6,7,8-tetrahydropteroyl-L-glutamic acid 5-Methyl-tetrahydrofolate 5-Methyl-tetrahydrofolic acid 5-Methyl-THF 5-Methyltetrahydrofolate 5-Methyltetrahydropteroylglutamate 5-Methyltetrahydropteroylglutamic acid Me-THF Methyl folate Methyl folic acid Methyl-H4F Methyl-tetrahydrofolate Methyl-tetrahydrofolic acid Methyl-THF N( 5)-Methyltetrahydrofolate N( 5)-Methyltetrahydrofolic acid N-(4-(((2-Amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-Glutamate N-(4-(((2-Amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-Glutamic acid N-(5-Methyl-5,6,7,8-tetrahydropteroyl)-L-glutamate N-(5-Methyl-5,6,7,8-tetrahydropteroyl)-L-glutamic acid N5-Methyl-tetrahydrofolate N5-Methyl-tetrahydrofolic acid N5-methyl-THF N5-methyltetrahydrofolate N5-methyltetrahydrofolic acid N5-methyltetrahydropteroyl mono-L-glutamate N5-methyltetrahydropteroyl mono-L-glutamic acid [(6S)-5-methyl-5,6,7,8-tetrahydropteroyl]glutamate [(6S)-5-methyl-5,6,7,8-tetrahydropteroyl]glutamic acid C20H25N7O6 459.4558 459.186631567 (2S)-2-{[4-({[(6S)-2-amino-5-methyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid 5-methyltetrahydrofolate 134-35-0 CN1C(CNC2=CC=C(C=C2)C(=O)N[C@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)NC(N)=N2 InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12?,13-/m1/s1 ZNOVTXRBGFNYRX-ZGTCLIOFSA-N Solid Cytosol logp -0.58 ALOGPS logs -3.14 ALOGPS solubility 3.32e-01 g/l ALOGPS logp -3.8 ChemAxon pka_strongest_acidic 3.5 ChemAxon pka_strongest_basic 3.54 ChemAxon iupac (2S)-2-{[4-({[(6S)-2-amino-5-methyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid ChemAxon average_mass 459.4558 ChemAxon mono_mass 459.186631567 ChemAxon smiles CN1C(CNC2=CC=C(C=C2)C(=O)N[C@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)NC(N)=N2 ChemAxon formula C20H25N7O6 ChemAxon inchi InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12?,13-/m1/s1 ChemAxon inchikey ZNOVTXRBGFNYRX-ZGTCLIOFSA-N ChemAxon polar_surface_area 198.48 ChemAxon refractivity 126.68 ChemAxon polarizability 46.56 ChemAxon rotatable_bond_count 9 ChemAxon acceptor_count 12 ChemAxon donor_count 7 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Reductive carboxylate cycle (CO2 fixation) ec00720 Cysteine and methionine metabolism ec00270 Methane metabolism ec00680 Selenoamino acid metabolism ec00450 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 Microbial metabolism in diverse environments ec01120 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 S-adenosyl-L-methionine cycle The S-adenosyl-L-methionine cycle starts with S-adenosyl-L-methionine reacting with (a demethylated methyl donor ) dimethylglycine resulting in the release of a hydrogen ion, a betain (a methylated methyl donor) and a S-adenosyl-L-homocysteine. The s-adenosyl-L-homocysteine reacts with a water molecule through a S-adenosylhomocysteine nucleosidase resulting in the release of a adenine and a ribosyl-L-homocysteine. This compound in turn reacts with a s-ribosylhomocysteine lyase resulting in the release of a l-homocysteine and a autoinducer 2. The L-homocysteine reacts with a N5-methyl-tetrahydropteroyl tri-L-glutamate through a methionine synthase resulting in the release of a tetrahydropteroyl tri-L-glutamate and a methione. The methionine in turn reacts with a water molecule and ATP molecule through a methionine adenosyltransferase resulting in the release of a diphosphate, a phosphate and a s-adenosyl-L-methionine. PW002080 Metabolic formylTHF biosynthesis I 1CMET2-PWY methionine biosynthesis I HOMOSER-METSYN-PWY Specdb::CMs 1083332 Specdb::EiMs 3942 Specdb::MsMs 23384 Specdb::MsMs 23385 Specdb::MsMs 23386 Specdb::MsMs 30182 Specdb::MsMs 30183 Specdb::MsMs 30184 HMDB01396 439234 388371 C00440 15641 5-METHYL-THF THH 5-Methyltetrahydrofolate 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 Gennari, Federico. Process for producing 5-methyltetrahydrofolic acid and its salts. U.S. (1992), 6 pp. 5,10-methylenetetrahydrofolate reductase P0AEZ1 METF_ECOLI metF http://ecmdb.ca/proteins/P0AEZ1.xml Methionine synthase P13009 METH_ECOLI metH http://ecmdb.ca/proteins/P13009.xml 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase P25665 METE_ECOLI metE http://ecmdb.ca/proteins/P25665.xml 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid R00946 HOMOCYSMETB12-RXN 2 Hydrogen ion + 5,10-Methylene-THF + NADH > 5-Methyltetrahydrofolic acid + NAD R07168 1.5.1.20-RXN 5-Methyltetrahydrofolic acid + L-Homocysteine <> Tetrahydrofolic acid + L-Methionine R00946 5-Methyltetrahydrofolic acid + NADP <> 5,10-Methylene-THF + NADPH + Hydrogen ion R01224 5-Methyltetrahydrofolic acid + NAD <> 5,10-Methylene-THF + NADH + Hydrogen ion R07168 1.5.1.20-RXN L-Homocysteine + 5-Methyltetrahydrofolic acid L-Methionine + Tetrahydrofolic acid HOMOCYSMETB12-RXN 5-Methyltetrahydrofolic acid + NAD(P)(+) > 5,10-Methylene-THF + NAD(P)H 5-Methyltetrahydrofolic acid + L-Homocysteine > Tetrahydrofolic acid + L-Methionine 5-Methyltetrahydrofolic acid + NAD + NADP <> 5,10-Methylene-THF + NADH + NADPH + Hydrogen ion R01224 R07168 5,10-Methylene-THF + NADPH + Hydrogen ion + 5,10-Methylene-THF + NADPH > 5-Methyltetrahydrofolic acid + NADP + 5-Methyltetrahydrofolic acid PW_R002541 5-Methyltetrahydrofolic acid + Homocysteine + 5-Methyltetrahydrofolic acid + Homocysteine > Tetrahydrofolic acid + L-Methionine + Tetrahydrofolic acid PW_R002542 2 Hydrogen ion + 5 5,10-Methylene-THF + NADH >5 5-Methyltetrahydrofolic acid + NAD 5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid 2 Hydrogen ion + 5 5,10-Methylene-THF + NADH >5 5-Methyltetrahydrofolic acid + NAD 5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid