Record Information
Version1.0
Created at2020-04-17 19:10:48 UTC
Updated at2020-12-07 19:11:37 UTC
CannabisDB IDCDB005115
Secondary Accession NumbersNot Available
Cannabis Compound Identification
Common NameTetrahydrofolic acid
DescriptionTetrahydrofolic acid, also known as tetrahydrofolate, belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety. Tetrahydrofolic acid is a moderately basic compound (based on its pKa). Tetrahydrofolic acid exists in all eukaryotes, ranging from yeast to humans. Many bacteria use dihydropteroate synthetase to produce dihydropteroate, a molecule without function in humans. Within humans, tetrahydrofolic acid participates in a number of enzymatic reactions. In particular, tetrahydrofolic acid can be converted into dihydrofolic acid; which is mediated by the enzyme dihydrofolate reductase. In addition, tetrahydrofolic acid and formic acid can be converted into 10-formyltetrahydrofolate; which is mediated by the enzyme C-1-tetrahydrofolate synthase, cytoplasmic. In humans, tetrahydrofolic acid is involved in the metabolic disorder called the methylenetetrahydrofolate reductase deficiency (mthfrd) pathway. 10-formyltetrahydrofolate acts as a donor of a group with one carbon atom. Methotrexate acts on dihydrofolate reductase, like pyrimethamine or trimethoprim, as an inhibitor and thus reduces the amount of tetrahydrofolate made. Tetrahydrofolic acid is involved in the conversion of formiminoglutamic acid to glutamic acid; this may reduce the amount of histidine available for decarboxylation and protein synthesis, and hence the urinary histamine and formiminoglutamic acid may be decreased. Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative. Tetrahydrofolic acid is a cofactor in many reactions, especially in the synthesis (or anabolism) of amino acids and nucleic acids. This may result in megaloblastic anemia. A shortage in tetrahydrofolic acid (FH4) can cause megaloblastic anemia. Tetrahydrofolic acid is expected to be in Cannabis as all living plants are known to produce and metabolize it.
Structure
Thumb
Synonyms
ValueSource
TetrahydrofolateGenerator
(6S)-TetrahydrofolateHMDB
(6S)-Tetrahydrofolic acidHMDB
5,6,7,8-TetrahydrofolateHMDB
5,6,7,8-Tetrahydrofolic acidHMDB
Tetra-H-folateHMDB
TetrahydrafolateHMDB
Tetrahydropteroyl mono-L-glutamateHMDB
TetrahydropteroylglutamateHMDB
Chemical FormulaC19H23N7O6
Average Molecular Weight445.43
Monoisotopic Molecular Weight445.171
IUPAC Name2-{[4-({[(6S)-4-hydroxy-2-imino-1,2,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
Traditional Name2-{[4-({[(6S)-4-hydroxy-2-imino-5,6,7,8-tetrahydro-1H-pteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
CAS Registry Number135-16-0
SMILES
NC1=NC(=O)C2=C(NC[C@H](CNC3=CC=C(C=C3)C(=O)NC(CCC(O)=O)C(O)=O)N2)N1
InChI Identifier
InChI=1S/C19H23N7O6/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/h1-4,11-12,21,23H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t11-,12?/m0/s1
InChI KeyMSTNYGQPCMXVAQ-PXYINDEMSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentXanthines
Alternative Parents
Substituents
  • Xanthine
  • Purinone
  • 6-oxopurine
  • Alkaloid or derivatives
  • Pyrimidone
  • Pyrimidine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Azole
  • Urea
  • Lactam
  • Azacycle
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Source:

Biological location:

Role

Industrial application:

Physical Properties
StateNot Available
Experimental Properties
PropertyValueReference
Melting Point250 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.27 g/LNot Available
logP-2.7Not Available
Predicted Properties
PropertyValueSource
logP-0.96ALOGPS
logP-3.6ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)2.04ChemAxon
pKa (Strongest Basic)5.76ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area208.26 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity132.4 m³·mol⁻¹ChemAxon
Polarizability44.57 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
EI-MS/GC-MS
TypeDescriptionSplash KeyView
Predicted GC-MSTetrahydrofolic acid, non-derivatized, Predicted GC-MS Spectrum - 70eV, Positivesplash10-0uka-4676900000-780e78301e85c240ab73Spectrum
Predicted GC-MSTetrahydrofolic acid, 2 TMS, Predicted GC-MS Spectrum - 70eV, Positivesplash10-006x-1311190000-af98cc8be4da08f9b782Spectrum
MS/MS
TypeDescriptionSplash KeyView
MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0002-7796610000-0937514a7f23431b726eSpectrum
MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0nor-3269210000-20105ed6a7a6e24e2441Spectrum
MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00kr-1935200000-a9449c19c1ae3b0d70daSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0032-0431900000-ff1f3948e47561161293Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0952300000-ed9d84bc39d490f6210eSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-0920000000-0d0efcb6c323340d20b9Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0001900000-abb4cec0eb79b0bd2de1Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0v4l-2356900000-2fd17d2f587bbd5e882cSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9441000000-8c630c7a3633467d6bb3Spectrum
NMR
TypeDescriptionView
1D NMR1H NMR SpectrumSpectrum
2D NMR[1H,1H] 2D NMR SpectrumSpectrum
2D NMR[1H,13C] 2D NMR SpectrumSpectrum
Pathways
Pathways
Protein Targets
Enzymes
Protein NameGene NameLocusUniprot IDDetails
Methionine synthaseMTR1q43Q99707 details
Methylenetetrahydrofolate reductaseMTHFR1p36.3P42898 details
Trifunctional purine biosynthetic protein adenosine-3GART21q22.11P22102 details
Formimidoyltransferase-cyclodeaminaseFTCD21q22.3O95954 details
Aminomethyltransferase, mitochondrialAMT3p21.2-p21.1P48728 details
Dihydrofolate reductaseDHFR5q11.2-q13.2P00374 details
Serine hydroxymethyltransferase, mitochondrialSHMT212q12-q14P34897 details
Serine hydroxymethyltransferase, cytosolicSHMT117p11.2P34896 details
Folylpolyglutamate synthase, mitochondrialFPGS9q34.1Q05932 details
Bifunctional purine biosynthesis protein PURHATIC2q35P31939 details
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialMTHFD22p13.1P13995 details
C-1-tetrahydrofolate synthase, cytoplasmicMTHFD114q24P11586 details
Cytosolic 10-formyltetrahydrofolate dehydrogenaseALDH1L13q21.3O75891 details
Glycine cleavage system H protein, mitochondrialGCSHP23434 details
Gamma-glutamyl hydrolaseGGH8q12.3Q92820 details
Mitochondrial 10-formyltetrahydrofolate dehydrogenaseALDH1L212q23.3Q3SY69 details
Methionyl-tRNA formyltransferase, mitochondrialMTFMT15q22.31Q96DP5 details
Monofunctional C1-tetrahydrofolate synthase, mitochondrialMTHFD1L6q25.1Q6UB35 details
Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolaseMTHFD22p13.1Q7Z650 details
Dihydrofolate reductase, mitochondrialDHFRL13q11.1Q86XF0 details
HemK methyltransferase family member 1HEMK1Q9Y5R4 details
Methyltransferase-like protein 2BMETTL2BQ6P1Q9 details
Methyltransferase-like protein 6METTL6Q8TCB7 details
Uncharacterized methyltransferase WBSCR22WBSCR22O43709 details
Transporters
Protein NameGene NameLocusUniprot IDDetails
Cytosolic 10-formyltetrahydrofolate dehydrogenaseALDH1L13q21.3O75891 details
Mitochondrial 10-formyltetrahydrofolate dehydrogenaseALDH1L212q23.3Q3SY69 details
Metal Bindings
Protein NameGene NameLocusUniprot IDDetails
Methionine synthaseMTR1q43Q99707 details
Trifunctional purine biosynthetic protein adenosine-3GART21q22.11P22102 details
ReceptorsNot Available
Transcriptional Factors
Protein NameGene NameLocusUniprot IDDetails
Dihydrofolate reductaseDHFR5q11.2-q13.2P00374 details
Concentrations Data
Not Available
HMDB IDHMDB0001846
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022705
KNApSAcK IDNot Available
Chemspider ID82572
KEGG Compound IDC00101
BioCyc IDTHF
BiGG ID33856
Wikipedia LinkTetrahydrofolic acid
METLIN ID714
PubChem Compound91443
PDB IDNot Available
ChEBI ID20506
References
General ReferencesNot Available

Only showing the first 10 proteins. There are 29 proteins in total.

Enzymes

General function:
Involved in cobalamin binding
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 (By similarity).
Gene Name:
MTR
Uniprot ID:
Q99707
Molecular weight:
140525.91
General function:
Involved in methylenetetrahydrofolate reductase (NADPH) activity
Specific function:
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name:
MTHFR
Uniprot ID:
P42898
Molecular weight:
74595.895
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
GART
Uniprot ID:
P22102
Molecular weight:
107766.295
General function:
Involved in catalytic activity
Specific function:
Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool. Binds and promotes bundling of vimentin filaments originating from the Golgi (By similarity).
Gene Name:
FTCD
Uniprot ID:
O95954
Molecular weight:
58925.93
General function:
Involved in aminomethyltransferase activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine.
Gene Name:
AMT
Uniprot ID:
P48728
Molecular weight:
43945.65
General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular weight:
21452.61
General function:
Involved in catalytic activity
Specific function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Interconversion of serine and glycine. Associates with mitochondrial DNA.
Gene Name:
SHMT2
Uniprot ID:
P34897
Molecular weight:
54862.125
General function:
Involved in catalytic activity
Specific function:
Interconversion of serine and glycine.
Gene Name:
SHMT1
Uniprot ID:
P34896
Molecular weight:
53082.18
General function:
Involved in tetrahydrofolylpolyglutamate synthase activity
Specific function:
Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.
Gene Name:
FPGS
Uniprot ID:
Q05932
Molecular weight:
59173.37
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

Transporters

General function:
Involved in formyltetrahydrofolate dehydrogenase activity
Specific function:
Not Available
Gene Name:
ALDH1L1
Uniprot ID:
O75891
Molecular weight:
99752.535
General function:
Involved in formyltetrahydrofolate dehydrogenase activity
Specific function:
Not Available
Gene Name:
ALDH1L2
Uniprot ID:
Q3SY69
Molecular weight:
101744.98

Only showing the first 10 proteins. There are 29 proteins in total.