Cannabis Compound Database: Showing Compound Card for Tetrahydrofolic acid (CDB005115)

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Record Information

Version

1.0

Created at

2020-04-17 19:10:48 UTC

Updated at

2020-12-07 19:11:37 UTC

CannabisDB ID

CDB005115

Secondary Accession Numbers

Not Available

Cannabis Compound Identification

Common Name

Tetrahydrofolic acid

Description

Tetrahydrofolic 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

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Tetrahydrofolate	Generator
(6S)-Tetrahydrofolate	HMDB
(6S)-Tetrahydrofolic acid	HMDB
5,6,7,8-Tetrahydrofolate	HMDB
5,6,7,8-Tetrahydrofolic acid	HMDB
Tetra-H-folate	HMDB
Tetrahydrafolate	HMDB
Tetrahydropteroyl mono-L-glutamate	HMDB
Tetrahydropteroylglutamate	HMDB

Chemical Formula

C₁₉H₂₃N₇O₆

Average Molecular Weight

445.43

Monoisotopic Molecular Weight

445.171

IUPAC Name

2-{[4-({[(6S)-4-hydroxy-2-imino-1,2,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid

Traditional Name

2-{[4-({[(6S)-4-hydroxy-2-imino-5,6,7,8-tetrahydro-1H-pteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid

CAS Registry Number

135-16-0

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 Key

MSTNYGQPCMXVAQ-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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Imidazopyrimidines

Sub Class

Purines and purine derivatives

Direct Parent

Xanthines

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

purine alkaloid (CHEBI:27732 )
trimethylxanthine (CHEBI:27732 )
Purine alkaloids (C07481 )
a small molecule (1-3-7-TRIMETHYLXANTHINE )

Ontology

Disposition

Source:

Endogenous

Biological location:

Role

Industrial application:

Drug

Food and nutrition:

Nutritional supplement

Physical Properties

State

Not Available

Experimental Properties

Property	Value	Reference
Melting Point	250 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	0.27 g/L	Not Available
logP	-2.7	Not Available

Predicted Properties

Property	Value	Source
logP	-0.96	ALOGPS
logP	-3.6	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	2.04	ChemAxon
pKa (Strongest Basic)	5.76	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	12	ChemAxon
Hydrogen Donor Count	9	ChemAxon
Polar Surface Area	208.26 Å²	ChemAxon
Rotatable Bond Count	9	ChemAxon
Refractivity	132.4 m³·mol⁻¹	ChemAxon
Polarizability	44.57 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	No	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

EI-MS/GC-MS

Type	Description	Splash Key	View
Predicted GC-MS	Tetrahydrofolic acid, non-derivatized, Predicted GC-MS Spectrum - 70eV, Positive	splash10-0uka-4676900000-780e78301e85c240ab73	Spectrum
Predicted GC-MS	Tetrahydrofolic acid, 2 TMS, Predicted GC-MS Spectrum - 70eV, Positive	splash10-006x-1311190000-af98cc8be4da08f9b782	Spectrum
Predicted GC-MS	Tetrahydrofolic acid, non-derivatized, Predicted GC-MS Spectrum - 70eV, Positive	Not Available	Spectrum

MS/MS

Type	Description	Splash Key	View
MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-0002-7796610000-0937514a7f23431b726e	2018-05-25	View Spectrum
MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0nor-3269210000-20105ed6a7a6e24e2441	2018-05-25	View Spectrum
MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-00kr-1935200000-a9449c19c1ae3b0d70da	2018-05-25	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0032-0431900000-ff1f3948e47561161293	2016-06-03	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001i-0952300000-ed9d84bc39d490f6210e	2016-06-03	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-0920000000-0d0efcb6c323340d20b9	2016-06-03	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-0001900000-abb4cec0eb79b0bd2de1	2016-08-03	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0v4l-2356900000-2fd17d2f587bbd5e882c	2016-08-03	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9441000000-8c630c7a3633467d6bb3	2016-08-03	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0080900000-73480c24ce118e5e02f3	2021-09-23	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-0491100000-0b5df4d0f168f8f15275	2021-09-23	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0089-0962000000-9a988cf519f340f5d7cf	2021-09-23	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-005c-0002900000-9587282a39f915386f95	2021-09-24	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0zi3-2807900000-28355749389d1e225f7b	2021-09-24	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0udi-3911000000-e7b1ccb0c9f2d7c8269a	2021-09-24	View Spectrum

NMR

Type	Description	View
1D NMR	¹H NMR Spectrum (1D, 600 MHz, H₂O, experimental)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Spectrum
2D NMR	[¹H, ¹H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)	Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Spectrum

Pathways

Name	SMPDB/Pathwhiz	KEGG
Pterine Biosynthesis
Folate Metabolism
Glycine and Serine Metabolism
Betaine Metabolism
Histidine Metabolism

Protein Targets

Enzymes

Protein Name	Gene Name	Locus	Uniprot ID	Details
Methionine synthase	MTR	1q43	Q99707	details
Methylenetetrahydrofolate reductase	MTHFR	1p36.3	P42898	details
Trifunctional purine biosynthetic protein adenosine-3	GART	21q22.11	P22102	details
Formimidoyltransferase-cyclodeaminase	FTCD	21q22.3	O95954	details
Aminomethyltransferase, mitochondrial	AMT	3p21.2-p21.1	P48728	details
Dihydrofolate reductase	DHFR	5q11.2-q13.2	P00374	details
Serine hydroxymethyltransferase, mitochondrial	SHMT2	12q12-q14	P34897	details
Serine hydroxymethyltransferase, cytosolic	SHMT1	17p11.2	P34896	details
Folylpolyglutamate synthase, mitochondrial	FPGS	9q34.1	Q05932	details
Bifunctional purine biosynthesis protein PURH	ATIC	2q35	P31939	details
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial	MTHFD2	2p13.1	P13995	details
C-1-tetrahydrofolate synthase, cytoplasmic	MTHFD1	14q24	P11586	details
Cytosolic 10-formyltetrahydrofolate dehydrogenase	ALDH1L1	3q21.3	O75891	details
Glycine cleavage system H protein, mitochondrial	GCSH		P23434	details
Gamma-glutamyl hydrolase	GGH	8q12.3	Q92820	details
Mitochondrial 10-formyltetrahydrofolate dehydrogenase	ALDH1L2	12q23.3	Q3SY69	details
Methionyl-tRNA formyltransferase, mitochondrial	MTFMT	15q22.31	Q96DP5	details
Monofunctional C1-tetrahydrofolate synthase, mitochondrial	MTHFD1L	6q25.1	Q6UB35	details
Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase	MTHFD2	2p13.1	Q7Z650	details
Dihydrofolate reductase, mitochondrial	DHFRL1	3q11.1	Q86XF0	details
HemK methyltransferase family member 1	HEMK1		Q9Y5R4	details
Methyltransferase-like protein 2B	METTL2B		Q6P1Q9	details
Methyltransferase-like protein 6	METTL6		Q8TCB7	details
Uncharacterized methyltransferase WBSCR22	WBSCR22		O43709	details

Transporters

Protein Name	Gene Name	Locus	Uniprot ID	Details
Cytosolic 10-formyltetrahydrofolate dehydrogenase	ALDH1L1	3q21.3	O75891	details
Mitochondrial 10-formyltetrahydrofolate dehydrogenase	ALDH1L2	12q23.3	Q3SY69	details

Metal Bindings

Protein Name	Gene Name	Locus	Uniprot ID	Details
Methionine synthase	MTR	1q43	Q99707	details
Trifunctional purine biosynthetic protein adenosine-3	GART	21q22.11	P22102	details

Receptors

Not Available

Transcriptional Factors

Protein Name	Gene Name	Locus	Uniprot ID	Details
Dihydrofolate reductase	DHFR	5q11.2-q13.2	P00374	details

Concentrations Data

Not Available

External Links

HMDB ID

HMDB0001846

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FoodDB ID

FDB022705

KNApSAcK ID

Not Available

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Wikipedia Link

METLIN ID

PubChem Compound

PDB ID

Not Available

ChEBI ID

20506

References

General References

Not Available

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

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Enzymes

Enzyme Details

1. Methionine synthase

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

Enzyme Details

2. Methylenetetrahydrofolate reductase

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

Enzyme Details

3. Trifunctional purine biosynthetic protein adenosine-3

General function:: Involved in catalytic activity
Specific function:: Not Available
Gene Name:: GART
Uniprot ID:: P22102
Molecular weight:: 107766.295

Enzyme Details

4. Formimidoyltransferase-cyclodeaminase

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

Enzyme Details

5. Aminomethyltransferase, mitochondrial

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

Enzyme Details

6. Dihydrofolate reductase

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

Enzyme Details

7. Serine hydroxymethyltransferase, mitochondrial

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

Enzyme Details

8. Serine hydroxymethyltransferase, cytosolic

General function:: Involved in catalytic activity
Specific function:: Interconversion of serine and glycine.
Gene Name:: SHMT1
Uniprot ID:: P34896
Molecular weight:: 53082.18

Enzyme Details

9. Folylpolyglutamate synthase, mitochondrial

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

Enzyme Details

10. Bifunctional purine biosynthesis protein PURH

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

Enzyme Details

1. Cytosolic 10-formyltetrahydrofolate dehydrogenase

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

Enzyme Details

2. Mitochondrial 10-formyltetrahydrofolate dehydrogenase

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.

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Showing Compound Card for Tetrahydrofolic acid (CDB005115)

Structure for CDB005115 (Tetrahydrofolic acid)

Enzymes

Transporters