Record Information
Version 1.0
Update Date 1/22/2018 12:54:54 PM
Metabolite IDPAMDB000424
Name: Tetrahydrofolic acid
Description:Tetrahydrofolate is a soluble coenzyme (vitamin B9) that is synthesized de novo by plants and microorganisms, and absorbed from the diet by animals. It is composed of three distinct parts: a pterin ring, a p-ABA (p-aminobenzoic acid) and a polyglutamate chain with a number of residues varying between 1 and 8. Only the tetra-reduced form of the molecule serves as a coenzyme for C1 transfer reactions. In biological systems, the C1-units exist under various oxidation states and the different tetrahydrofolate derivatives constitute a family of related molecules named indistinctly under the generic term folate. (PMID 16042593)
  • (6S)-Tetrahydrofolate
  • (6S)-Tetrahydrofolic acid
  • 5,6,7,8-Tetrahydrofolate
  • 5,6,7,8-Tetrahydrofolic acid
  • FH4
  • Folate-H4
  • Folic acid-H4
  • H4F
  • H4PteGlu
  • H4PteGlu1
  • H4PteGlu1
  • Tetra-H-folate
  • Tetra-H-folic acid
  • Tetrahydrafolate
  • Tetrahydrafolic acid
  • Tetrahydrofolate
  • Tetrahydrofolic acid
  • Tetrahydropteroyl mono-L-glutamate
  • Tetrahydropteroyl mono-L-glutamic acid
  • Tetrahydropteroylglutamate
  • Tetrahydropteroylglutamic acid
  • Th-folate
  • Th-folic acid
  • THF
  • Vitamin B9
Chemical Formula: C19H23N7O6
Average Molecular Weight: 445.4292
Monoisotopic Molecular Weight: 445.170981503
CAS number: 135-16-0
IUPAC Name:(2S)-2-{[4-({[(6S)-4-hydroxy-2-imino-1,2,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
Traditional IUPAC Name: (2S)-2-{[4-({[(6S)-4-hydroxy-2-imino-5,6,7,8-tetrahydro-1H-pteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
Chemical Taxonomy
Taxonomy DescriptionThis compound belongs to the class of organic compounds known as hippuric acids. These are compounds containing hippuric acid, which consists of a of a benzoyl group linked to the N-terminal of a glycine.
Kingdom Organic compounds
Super ClassBenzenoids
Class Benzene and substituted derivatives
Sub ClassBenzamides
Direct Parent Hippuric acids
Alternative Parents
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Pterin
  • Pteridine
  • Aminobenzoic acid or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Benzoic acid or derivatives
  • Aminobenzamide
  • Phenylalkylamine
  • Substituted aniline
  • Benzoyl
  • Hydroxypyrimidine
  • Secondary aliphatic/aromatic amine
  • Aniline
  • Amino fatty acid
  • Fatty acyl
  • Pyrimidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular Framework Aromatic heteropolycyclic compounds
External Descriptors
Physical Properties
State: Solid
Melting point: 250 °C (523 K), decomp.
Experimental Properties:
Predicted Properties
Water Solubility0.215 mg/mLALOGPS
pKa (Strongest Acidic)-13ChemAxon
pKa (Strongest Basic)15ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area208.26 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity132.4 m3·mol-1ChemAxon
Polarizability44.33 Å3ChemAxon
Number of Rings3ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations: Cytoplasm
Dihydrofolic acid + Hydrogen ion + NADPH <> NADP + Tetrahydrofolic acid
Glycine + NAD + Tetrahydrofolic acid > Carbon dioxide + 5,10-Methylene-THF + NADH + Ammonium
5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acid
alpha-Ketoisovaleric acid + Water + 5,10-Methylene-THF + a-Ketoisovaleric acid <> 2-Dehydropantoate + Tetrahydrofolic acid
N10-Formyl-THF + Water <> Formic acid + Hydrogen ion + Tetrahydrofolic acid
N10-Formyl-THF + Uridine 5''-diphospho-{beta}-4-deoxy-4-amino-L-arabinose <> Hydrogen ion + Tetrahydrofolic acid + Uridine 5''-diphospho-{beta}-4-deoxy-4-formamido-L-arabinose
N10-Formyl-THF + Glycineamideribotide <> 5'-Phosphoribosyl-N-formylglycineamide + Hydrogen ion + Tetrahydrofolic acid
L-Serine + Tetrahydrofolic acid <> Glycine + Water + 5,10-Methylene-THF
N10-Formyl-THF + L-Methionyl-tRNA (Met) > N-Formylmethionyl-tRNA + Hydrogen ion + Tetrahydrofolic acid
N10-Formyl-THF + Phosphoribosyl formamidocarboxamide <> Phosphoribosyl formamidocarboxamide + Tetrahydrofolic acid
Tetrahydrofolic acid + NAD <> Dihydrofolic acid + NADH + Hydrogen ion
Tetrahydrofolic acid + 2 NAD <> Folic acid +2 NADH +2 Hydrogen ion
Tetrahydrofolic acid + 2 NADP <> Folic acid +2 NADPH +2 Hydrogen ion
Adenosine triphosphate + Tetrahydrofolic acid + L-Glutamate <> ADP + Phosphate + Tetrahydrofolyl-[Glu](2)
N10-Formyl-THF + Water <> Formic acid + Tetrahydrofolic acid
5-Methyltetrahydrofolic acid + L-Homocysteine <> Tetrahydrofolic acid + L-Methionine
Glycine + Tetrahydrofolic acid + NAD <> 5,10-Methylene-THF + Ammonia + Carbon dioxide + NADH + Hydrogen ion
L-Methionyl-tRNA + N10-Formyl-THF <> Tetrahydrofolic acid + N-Formylmethionyl-tRNA
S-Aminomethyldihydrolipoylprotein + Tetrahydrofolic acid + S-Aminomethyldihydrolipoylprotein <> Dihydrolipoylprotein + 5,10-Methylene-THF + Ammonia
N10-Formyl-THF + Glycineamideribotide <> Tetrahydrofolic acid + 5'-Phosphoribosyl-N-formylglycineamide
Glycineamideribotide + 5,10-Methenyltetrahydrofolate + Water <> 5'-Phosphoribosyl-N-formylglycineamide + Tetrahydrofolic acid
N10-Formyl-THF + AICAR <> Tetrahydrofolic acid + Phosphoribosyl formamidocarboxamide
N10-Formyl-THF + Uridine 5''-diphospho-{beta}-4-deoxy-4-amino-L-arabinose <> Tetrahydrofolic acid + Uridine 5''-diphospho-{beta}-4-deoxy-4-formamido-L-arabinose
Formaldehyde + Tetrahydrofolic acid > 5,10-Methylene-THF + Water
Water + alpha-Ketoisovaleric acid + 5,10-Methylene-THF <> 2-Dehydropantoate + Tetrahydrofolic acid
Adenosine triphosphate + Formic acid + Tetrahydrofolic acid > ADP + Phosphate + N10-Formyl-THF
N10-Formyl-THF + 4-Amino-4-deoxy-L-arabinose > Tetrahydrofolic acid + UDP-4-Deoxy-4-formamido-beta-L-arabinose
Tetrahydrofolic acid + NADP > Dihydrofolic acid + NADPH
N10-Formyl-THF + L-methionyl-tRNA(fMet) > Tetrahydrofolic acid + N-formylmethionyl-tRNA(fMet)
[Protein]-S(8)-aminomethyldihydrolipoyllysine + Tetrahydrofolic acid > [protein]-dihydrolipoyllysine + 5,10-Methylene-THF + Ammonia
5,10-Methylene-THF + a-Ketoisovaleric acid + Water > Tetrahydrofolic acid + 2-Dehydropantoate
Dihydrofolic acid + NADPH + Hydrogen ion + Dihydrofolic acid + NADPH > Tetrahydrofolic acid + NADP + Tetrahydrofolic acid
7,8-dihydrofolate monoglutamate + Hydrogen ion + NADPH + Dihydrofolic acid + NADPH > NADP + Tetrahydrofolic acid + Tetrahydrofolic acid
Folic acid + 2 NADPH + 2 Hydrogen ion + 2 NADPH > Tetrahydrofolic acid +2 NADP + Tetrahydrofolic acid
5-Methyltetrahydrofolic acid + Homocysteine + 5-Methyltetrahydrofolic acid + Homocysteine > Tetrahydrofolic acid + L-Methionine + Tetrahydrofolic acid
S-Aminomethyldihydrolipoylprotein; + Tetrahydrofolic acid + Tetrahydrofolic acid <> 5,10-Methylene-THF + Ammonia + dihydrolipoylprotein + 5,10-Methylene-THF
Tetrahydrofolic acid + L-Serine + Tetrahydrofolic acid + L-Serine <> 5,10-Methylene-THF + Glycine + Water + 5,10-Methylene-THF
Tetrahydrofolic acid + FAICAR + Tetrahydrofolic acid > 10-Formyltetrahydrofolate + AICAR + N10-Formyl-THF
Tetrahydrofolic acid + 5'-Phosphoribosyl-N-formylglycinamide + Tetrahydrofolic acid + 5'-Phosphoribosyl-N-formylglycineamide > Water + 5,10-Methenyltetrahydrofolic acid + Glycineamideribotide + Glycineamideribotide
Tetrahydrofolic acid + 5'-Phosphoribosyl-N-formylglycinamide + Tetrahydrofolic acid + 5'-Phosphoribosyl-N-formylglycineamide > 10-Formyltetrahydrofolate + Glycineamideribotide + N10-Formyl-THF + Glycineamideribotide
5'-phosphoribosyl-a-N-formylglycineamidine + Tetrahydrofolic acid + Tetrahydrofolic acid > Water + Glycineamideribotide + 5,10-Methenyltetrahydrofolic acid + Glycineamideribotide
Formic acid + Tetrahydrofolic acid + Tetrahydrofolic acid > Water + 10-Formyltetrahydrofolate + N10-Formyl-THF
Tetrahydrofolic acid + N-formylmethionyl-tRNA(fMet) + Tetrahydrofolic acid L-methionyl-tRNA(Met) + 10-Formyltetrahydrofolate + N10-Formyl-THF
a-Ketoisovaleric acid + 5,10-Methylene-THF + Water + 5,10-Methylene-THF > Tetrahydrofolic acid + 2-dehydropantoate + Tetrahydrofolic acid + 2-Dehydropantoate
Uridine 5''-diphospho-{beta}-4-deoxy-4-amino-L-arabinose + an N10-formyl-tetrahydrofolate + N10-Formyl-THF > UDP-4-Deoxy-4-formamido-beta-L-arabinose + Hydrogen ion + a tetrahydrofolate + Tetrahydrofolic acid

Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-005a-0321900000-806d326ed7665c62ee13View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0951300000-03607a01f0842f177170View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-0920000000-a669623379da5ac89208View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-002f-0001900000-535971052b80b0699a2eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fbc-1346900000-37b6b740cafe7f89f238View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9441000000-d269bea3204e174044ceView in MoNA
  • 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. Pubmed: 22080510
  • 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. Pubmed: 21097882
  • Sahr, T., Ravanel, S., Rebeille, F. (2005). "Tetrahydrofolate biosynthesis and distribution in higher plants." Biochem Soc Trans 33:758-762. Pubmed: 16042593
  • 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. Pubmed: 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. Pubmed: 18331064
Synthesis Reference: Not Available
Material Safety Data Sheet (MSDS) Download (PDF)
External Links:
Pubchem Compound ID1129
Kegg IDC00101
ChemSpider ID1097
WikipediaTetrahydrofolic acid
Ligand ExpoTHL


General function:
Involved in hydroxymethyl-, formyl- and related transferase activity
Specific function:
10-formyltetrahydrofolate + N(1)-(5-phospho-D- ribosyl)glycinamide = tetrahydrofolate + N(2)-formyl-N(1)-(5- phospho-D-ribosyl)glycinamide
Gene Name:
Locus Tag:
Molecular weight:
24.7 kDa
10-formyltetrahydrofolate + N(1)-(5-phospho-D-ribosyl)glycinamide = tetrahydrofolate + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide.
General function:
Involved in tetrahydrofolylpolyglutamate synthase activity
Specific function:
Conversion of folates to polyglutamate derivatives
Gene Name:
Locus Tag:
Molecular weight:
46.5 kDa
ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).
ATP + 7,8-dihydropteroate + L-glutamate = ADP + phosphate + 7,8-dihydropteroylglutamate.
General function:
Involved in catalytic activity
Specific function:
Interconversion of serine and glycine
Gene Name:
Locus Tag:
Molecular weight:
45.2 kDa
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine.
General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis
Gene Name:
Locus Tag:
Molecular weight:
18.2 kDa
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH.
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the reduction of dihydrofolate to tetrahydrofolate
Gene Name:
Locus Tag:
Molecular weight:
25.4 kDa
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH.
General function:
Involved in methionine synthase activity
Specific function:
Catalyzes the transfer of a methyl group from methyl- cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate
Gene Name:
Locus Tag:
Molecular weight:
135.1 kDa
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.
General function:
Involved in IMP cyclohydrolase activity
Specific function:
10-formyltetrahydrofolate + 5-amino-1-(5- phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5- formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
Gene Name:
Locus Tag:
Molecular weight:
57.7 kDa
10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.
IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.
General function:
Involved in methionyl-tRNA formyltransferase activity
Specific function:
Modifies the free amino group of the aminoacyl moiety of methionyl-tRNA(fMet). The formyl group appears to play a dual role in the initiator identity of N-formylmethionyl-tRNA by:(I) promoting its recognition by IF2 and (II) impairing its binding to EFTu-GTP
Gene Name:
Locus Tag:
Molecular weight:
33 kDa
10-formyltetrahydrofolate + L-methionyl-tRNA(fMet) + H(2)O = tetrahydrofolate + N-formylmethionyl-tRNA(fMet).
General function:
Involved in 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity
Specific function:
Catalyzes the transfer of a methyl group from 5- methyltetrahydrofolate to homocysteine resulting in methionine formation
Gene Name:
Locus Tag:
Molecular weight:
86.2 kDa
5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = tetrahydropteroyltri-L-glutamate + L-methionine.
General function:
Involved in aminomethyltransferase activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine
Gene Name:
Locus Tag:
Molecular weight:
38.9 kDa
[Protein]-S(8)-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH(3).
General function:
Involved in 3-methyl-2-oxobutanoate hydroxymethyltransferase activity
Specific function:
Catalyzes the reversible reaction in which hydroxymethyl group from 5,10-methylenetetrahydrofolate is tranferred onto alpha-ketoisovalerate to form ketopantoate
Gene Name:
Locus Tag:
Molecular weight:
27.9 kDa
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H(2)O = tetrahydrofolate + 2-dehydropantoate.
General function:
Involved in glycine dehydrogenase (decarboxylating) activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein
Gene Name:
Locus Tag:
Molecular weight:
104.7 kDa
Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2).
General function:
Involved in ATP binding
Specific function:
Catalyzes two reactions:the first one is the production of beta-formyl glycinamide ribonucleotide (GAR) from formate, ATP and beta GAR; the second, a side reaction, is the production of acetyl phosphate and ADP from acetate and ATP
Gene Name:
Locus Tag:
Molecular weight:
42.3 kDa
Formate + ATP + 5'-phospho-ribosylglycinamide = 5'-phosphoribosyl-N-formylglycinamide + ADP + diphosphate.
General function:
Involved in hydroxymethyl-, formyl- and related transferase activity
Specific function:
Bifunctional enzyme that catalyzes the oxidative decarboxylation of UDP-glucuronic acid (UDP-GlcUA) to UDP-4-keto- arabinose (UDP-Ara4O) and the addition of a formyl group to UDP-4- amino-4-deoxy-L-arabinose (UDP-L-Ara4N) to form UDP-L-4-formamido- arabinose (UDP-L-Ara4FN). The modified arabinose is attached to lipid A and is required for resistance to polymyxin and cationic antimicrobial peptides
Gene Name:
Locus Tag:
Molecular weight:
74.4 kDa
UDP-alpha-D-glucuronate + NAD(+) = UDP-beta-L-threo-pentapyranos-4-ulose + CO(2) + NADH.
10-formyltetrahydrofolate + UDP-4-amino-4-deoxy-beta-L-arabinose = 5,6,7,8-tetrahydrofolate + UDP-4-deoxy-4-formamido-beta-L-arabinose.
General function:
Amino acid transport and metabolism
Specific function:
The glycine cleavage system catalyzes the degradation of glycine. The H protein shuttles the methylamine group of glycine from the P protein to the T protein
Gene Name:
Locus Tag:
Molecular weight:
13.6 kDa