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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:03:38 UTC
HMDB IDHMDB00972
Secondary Accession NumbersNone
Metabolite Identification
Common Name10-Formyltetrahydrofolate
Description10-Formyltetrahydrofolate (10-CHO-THF) is form of tetrahydrofolate that acts as a donor of formyl groups in anabolism. In particular, 10-CHO-THF is used as a substrate in a number of formyltransferase reactions. It plays an important role in purine biosynthesis, where 10-CHO-THF is a substrate for phosphoribosylaminoimidazolecarboxamide formyltransferase, as well as in the formylation of the methionyl initiator tRNA (fMet-tRNA), when 10-CHO-THF is a substrate for methionyl-tRNA formyltransferase. 10-Formyltetrahydrofolate is a substrate for Trifunctional purine biosynthetic protein adenosine-3, Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (mitochondrial), 10-formyltetrahydrofolate dehydrogenase, Folylpolyglutamate synthase (mitochondrial), Bifunctional purine biosynthesis protein PURH and C-1-tetrahydrofolate synthase (cytoplasmic).
Structure
Thumb
Synonyms
ValueSource
10-Formyl-THFKegg
10-Formyltetrahydrofolic acidGenerator
10-Formyl-(6Rs)-tetrahydrofolic acidHMDB
10-Formyl-H4pteglu1HMDB
10-Formyl-tetrahydrofolateHMDB
10-FormyltetrahydropteroylglutamateHMDB
10-Formyltetrahydropteroylglutamic acidHMDB
10-FTHFHMDB
N-[P-[N-[(2-amino-5,6,7,8-tetrahydro-4-Hydroxy-6-pteridinyl)methyl]formamido]benzoyl]-glutamateHMDB
N-[P-[N-[(2-amino-5,6,7,8-tetrahydro-4-Hydroxy-6-pteridinyl)methyl]formamido]benzoyl]-glutamic acidHMDB
N-[P-[N-[(2-amino-5,6,7,8-tetrahydro-4-Hydroxy-6-pteridinyl)methyl]formamido]benzoyl]-L-glutamateHMDB
N-[P-[N-[(2-amino-5,6,7,8-tetrahydro-4-Hydroxy-6-pteridinyl)methyl]formamido]benzoyl]-L-glutamic acidHMDB
N10-Formyl-5,6,7,8-tetrahydrofolateHMDB
N10-Formyl-5,6,7,8-tetrahydrofolic acidHMDB
N10-Formyl-H4FHMDB
N10-Formyl-THFHMDB
N10-FormyltetrahydrofolateHMDB
N10-Formyltetrahydrofolic acidHMDB
N10-FormyltetrahydropteroylglutamateHMDB
Chemical FormulaC20H23N7O7
Average Molecular Weight473.4393
Monoisotopic Molecular Weight473.165896125
IUPAC Name(2S)-2-[(4-{N-[(2-amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]formamido}phenyl)formamido]pentanedioic acid
Traditional Name(2S)-2-[(4-{N-[(2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pteridin-6-yl)methyl]formamido}phenyl)formamido]pentanedioic acid
CAS Registry Number2800-34-2
SMILES
NC1=NC(=O)C2=C(NCC(CN(C=O)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2)N1
InChI Identifier
InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)23-11(7-22-16)8-27(9-28)12-3-1-10(2-4-12)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,11,13,23H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,22,25,26,32)/t11?,13-/m0/s1
InChI KeyInChIKey=AUFGTPPARQZWDO-YUZLPWPTSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassPterins and derivatives
Direct ParentTetrahydrofolic acids
Alternative Parents
Substituents
  • Tetrahydrofolic acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Aminobenzoic acid or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Benzoic acid or derivatives
  • Benzamide
  • Aminobenzamide
  • Benzoyl
  • Secondary aliphatic/aromatic amine
  • Pyrimidone
  • Amino fatty acid
  • Fatty acyl
  • Benzenoid
  • Pyrimidine
  • Primary aromatic amine
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary carboxylic acid amide
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Secondary amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Endogenous
Biofunction
  • Component of Glyoxylate and dicarboxylate metabolism
ApplicationNot Available
Cellular locations
  • Extracellular
  • Mitochondria
  • Lysosome
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.34 mg/mLALOGPS
logP-1.5ALOGPS
logP-4.4ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)2.73ChemAxon
pKa (Strongest Basic)3.58ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area215.55 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity124.68 m3·mol-1ChemAxon
Polarizability46.21 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Mitochondria
  • Lysosome
Biofluid LocationsNot Available
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Adenine phosphoribosyltransferase deficiency (APRT)SMP00535Not Available
Adenosine Deaminase DeficiencySMP00144Not Available
Adenylosuccinate Lyase DeficiencySMP00167Not Available
AICA-RibosiduriaSMP00168Not Available
Azathioprine PathwaySMP00427Not Available
Cystathionine Beta-Synthase DeficiencySMP00177Not Available
Folate malabsorption, hereditarySMP00724Not Available
Folate MetabolismSMP00053map00670
Glycine N-methyltransferase DeficiencySMP00222Not Available
Gout or Kelley-Seegmiller SyndromeSMP00365Not Available
Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation typeSMP00570Not Available
HypermethioninemiaSMP00341Not Available
Lesch-Nyhan Syndrome (LNS)SMP00364Not Available
Mercaptopurine PathwaySMP00428Not Available
Methionine Adenosyltransferase DeficiencySMP00221Not Available
Methionine MetabolismSMP00033map00270
Methotrexate PathwaySMP00432Not Available
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)SMP00543Not Available
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)SMP00340Not Available
Mitochondrial DNA depletion syndromeSMP00536Not Available
Molybdenum Cofactor DeficiencySMP00203Not Available
Myoadenylate deaminase deficiencySMP00537Not Available
Purine MetabolismSMP00050map00230
Purine Nucleoside Phosphorylase DeficiencySMP00210Not Available
S-Adenosylhomocysteine (SAH) Hydrolase DeficiencySMP00214Not Available
Thioguanine PathwaySMP00430Not Available
Xanthine Dehydrogenase Deficiency (Xanthinuria)SMP00220Not Available
Xanthinuria type ISMP00512Not Available
Xanthinuria type IISMP00513Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022345
KNApSAcK IDNot Available
Chemspider ID109092
KEGG Compound IDC00234
BioCyc ID10-FORMYL-THF
BiGG ID34337
Wikipedia Link10-formyl-tetrahydrofolate
NuGOwiki LinkHMDB00972
Metagene LinkHMDB00972
METLIN ID5912
PubChem Compound122347
PDB IDNot Available
ChEBI ID15637
References
Synthesis ReferenceDenis V; Daignan-Fornier B Synthesis of glutamine, glycine and 10-formyl tetrahydrofolate is coregulated with purine biosynthesis in Saccharomyces cerevisiae. Molecular & general genetics : MGG (1998), 259(3), 246-55.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Xu L, Li C, Olson AJ, Wilson IA: Crystal structure of avian aminoimidazole-4-carboxamide ribonucleotide transformylase in complex with a novel non-folate inhibitor identified by virtual ligand screening. J Biol Chem. 2004 Nov 26;279(48):50555-65. Epub 2004 Sep 7. [15355974 ]
  2. Baggott JE, Tamura T: Bioactivity of orally administered unnatural isomers, [6R]-5-formyltetrahydrofolate and [6S]-5,10-methenyltetrahydrofolate, in humans. Biochim Biophys Acta. 1999 Oct 18;1472(1-2):323-32. [10572954 ]
  3. Johlin FC, Swain E, Smith C, Tephly TR: Studies on the mechanism of methanol poisoning: purification and comparison of rat and human liver 10-formyltetrahydrofolate dehydrogenase. Mol Pharmacol. 1989 Jun;35(6):745-50. [2733692 ]
  4. Kirksey TJ, Appling DR: Site-directed mutagenesis of a highly conserved aspartate in the putative 10-formyl-tetrahydrofolate binding site of yeast C1-tetrahydrofolate synthase. Arch Biochem Biophys. 1996 Sep 1;333(1):251-9. [8806778 ]
  5. Baggott JE, Robinson CB, Johnston KE: Bioactivity of [6R]-5-formyltetrahydrofolate, an unusual isomer, in humans and Enterococcus hirae, and cytochrome c oxidation of 10-formytetrahydrofolate to 10-formyldihydrofolate. Biochem J. 2001 Feb 15;354(Pt 1):115-22. [11171086 ]
  6. Boger DL, Labroli MA, Marsilje TH, Jin Q, Hedrick MP, Baker SJ, Shim JH, Benkovic SJ: Conformationally restricted analogues designed for selective inhibition of GAR Tfase versus thymidylate synthase or dihydrofolate reductase. Bioorg Med Chem. 2000 May;8(5):1075-86. [10882019 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
GART
Uniprot ID:
P22102
Molecular weight:
107766.295
Reactions
10-Formyltetrahydrofolate + Glycineamideribotide → Tetrahydrofolic acid + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamidedetails
10-Formyltetrahydrofolate + Glycineamideribotide → Tetrahydrofolic acid + 5'-Phosphoribosyl-N-formylglycinamidedetails
General function:
Involved in IMP cyclohydrolase activity
Specific function:
Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.
Gene Name:
ATIC
Uniprot ID:
P31939
Molecular weight:
64615.255
Reactions
10-Formyltetrahydrofolate + AICAR → Tetrahydrofolic acid + Phosphoribosyl formamidocarboxamidedetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
MTHFD2
Uniprot ID:
P13995
Molecular weight:
37894.775
Reactions
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolatedetails
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolate + Hydrogen Iondetails
General function:
Involved in formate-tetrahydrofolate ligase activity
Specific function:
Not Available
Gene Name:
MTHFD1
Uniprot ID:
P11586
Molecular weight:
101530.36
Reactions
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolatedetails
Adenosine triphosphate + Formic acid + Tetrahydrofolic acid → ADP + Phosphoric acid + 10-Formyltetrahydrofolatedetails
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolate + Hydrogen Iondetails
General function:
Involved in formyltetrahydrofolate dehydrogenase activity
Specific function:
Not Available
Gene Name:
ALDH1L1
Uniprot ID:
O75891
Molecular weight:
99752.535
Reactions
10-Formyltetrahydrofolate + NADP + Water → Tetrahydrofolic acid + CO(2) + NADPHdetails
10-Formyltetrahydrofolate + NADP + Water → Tetrahydrofolic acid + Carbon dioxide + NADPH + Hydrogen Iondetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
MTHFD2L
Uniprot ID:
Q9H903
Molecular weight:
37315.11
Reactions
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolatedetails
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolate + Hydrogen Iondetails
General function:
Involved in formyltetrahydrofolate dehydrogenase activity
Specific function:
Not Available
Gene Name:
ALDH1L2
Uniprot ID:
Q3SY69
Molecular weight:
101744.98
Reactions
10-Formyltetrahydrofolate + NADP + Water → Tetrahydrofolic acid + CO(2) + NADPHdetails
10-Formyltetrahydrofolate + NADP + Water → Tetrahydrofolic acid + Carbon dioxide + NADPH + Hydrogen Iondetails
General function:
Involved in methionyl-tRNA formyltransferase activity
Specific function:
Formylates methionyl-tRNA in mitochondria. A single tRNA(Met) gene gives rise to both an initiator and an elongator species via an unknown mechanism (By similarity).
Gene Name:
MTFMT
Uniprot ID:
Q96DP5
Molecular weight:
43831.73
Reactions
10-Formyltetrahydrofolate + L-methionyl-tRNA(fMet) → Tetrahydrofolic acid + N-formylmethionyl-tRNA(fMet)details
L-Methionyl-tRNA + 10-Formyltetrahydrofolate → Tetrahydrofolic acid + N-Formylmethionyl-tRNAdetails
General function:
Involved in formate-tetrahydrofolate ligase activity
Specific function:
May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism in embryonic an transformed cells complementing thus the enzymatic activities of MTHFD2 (By similarity).
Gene Name:
MTHFD1L
Uniprot ID:
Q6UB35
Molecular weight:
105888.19
Reactions
Adenosine triphosphate + Formic acid + Tetrahydrofolic acid → ADP + Phosphoric acid + 10-Formyltetrahydrofolatedetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
MTHFD2
Uniprot ID:
Q7Z650
Molecular weight:
26849.1