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5,6,7,8-Tetrahydrofolic acid (YMDB00483)

Identification
YMDB IDYMDB00483
Name5,6,7,8-Tetrahydrofolic acid
SpeciesSaccharomyces cerevisiae
StrainBaker's yeast
Descriptiontetrahydrofolate, also known as (6S)-thfa, belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom. tetrahydrofolate is a strong basic compound (based on its pKa). tetrahydrofolate may be a unique S. cerevisiae (yeast) metabolite. tetrahydrofolate and UDP-4-deoxy-4-formamido-beta-L-arabinose can be biosynthesized from 10-formyltetrahydrofolate and 4-amino-4-deoxy-L-arabinose through its interaction with the enzyme UDP-L-ara4n formyltransferase / UDP-glca C-4"-decarboxylase. In yeast, tetrahydrofolate is involved in the metabolic pathway called the one carbon pool by folate I pathway.
Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
  • (6s)-tetrahydrofolate
  • (6s)-tetrahydrofolic acid
  • (6s)-thfa
  • 5,6,7,8-Tetrahydrofolate
  • 5,6,7,8-tetrahydrofolic acid
  • folate-H4
  • H4PteGlu
  • H4PteGlu1
  • tetra-H-folate
  • tetrahydrafolate
  • Tetrahydrofolate
  • tetrahydrofolic acid
  • tetrahydropteroyl mono-L-glutamate
  • tetrahydropteroylglutamate
  • th-folate
  • THF
  • thf, tetrahydrofolate
  • vitamin B9
  • 5,6,7,8-Tetrahydrofolic acid, (D-(-))-isomer
  • 5,6,7,8-Tetrahydrofolic acid, (L)-isomer
  • 5,6,7,8-Tetrahydrofolic acid, ion (2-)-isomer
CAS number135-16-0
WeightAverage: 445.4292
Monoisotopic: 445.170981503
InChI KeyMSTNYGQPCMXVAQ-KIYNQFGBSA-N
InChIInChI=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
IUPAC Name(2S)-2-[(4-{[(2-amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
Traditional IUPAC Nametetrahydrofolic acid
Chemical FormulaC19H23N7O6
SMILESNC1=NC2=C(NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CN2)C(=O)N1
Chemical Taxonomy
Description belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGlutamic acid and derivatives
Alternative Parents
Substituents
  • Glutamic acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Pterin
  • Aminobenzamide
  • Aminobenzoic acid or derivatives
  • Pteridine
  • Benzamide
  • Benzoic acid or derivatives
  • Aniline or substituted anilines
  • Benzoyl
  • Phenylalkylamine
  • Hydroxypyrimidine
  • Secondary aliphatic/aromatic amine
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Amino acid
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Organoheterocyclic compound
  • Azacycle
  • Carboxylic acid
  • Secondary amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Amine
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physical Properties
StateSolid
Charge0
Melting point250 °C
Experimental Properties
PropertyValueReference
Water SolubilityNot AvailablePhysProp
LogPNot AvailablePhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.27 g/LALOGPS
logP-0.96ALOGPS
logP-4.2ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.51ChemAxon
pKa (Strongest Basic)3.58ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area207.27 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity121.39 m³·mol⁻¹ChemAxon
Polarizability42.95 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations
  • mitochondrion
  • cytoplasm
Organoleptic PropertiesNot Available
SMPDB Pathways
One Carbon Pool by Folate IPW002468 ThumbThumb?image type=greyscaleThumb?image type=simple
Pantothenate and CoA biosynthesisPW002463 ThumbThumb?image type=greyscaleThumb?image type=simple
glycine metabolismPW002398 ThumbThumb?image type=greyscaleThumb?image type=simple
purine nucleotides de novo biosynthesisPW002478 ThumbThumb?image type=greyscaleThumb?image type=simple
serine metabolismPW002402 ThumbThumb?image type=greyscaleThumb?image type=simple
KEGG Pathways
Folate biosynthesisec00790 Map00790
Glycine, serine and threonine metabolismec00260 Map00260
Methane metabolismec00680 Map00680
One carbon pool by folateec00670 Map00670
Pantothenate and CoA biosynthesisec00770 Map00770
SMPDB ReactionsNot Available
KEGG Reactions
Alpha-Ketoisovaleric acid + water + 5,10-Methylene-THF → 2-Dehydropantoic acid + 5,6,7,8-Tetrahydrofolic acid
NADPH + hydron + Dihydrofolic acid → NADP + 5,6,7,8-Tetrahydrofolic acid
Adenosine triphosphate + 5,6,7,8-Tetrahydrofolic acid + Formic acid → N10-Formyl-THF + phosphate + ADP
NAD + Glycine + 5,6,7,8-Tetrahydrofolic acid → NADH + Carbon dioxide + 5,10-Methylene-THF + Ammonium
L-Serine + 5,6,7,8-Tetrahydrofolic acid ↔ Glycine + water + 5,10-Methylene-THF
Concentrations
Intracellular ConcentrationsNot Available
Extracellular ConcentrationsNot Available
Spectra
Spectra
References
References:
  • Herrgard, M. J., Swainston, N., Dobson, P., Dunn, W. B., Arga, K. Y., Arvas, M., Bluthgen, N., Borger, S., Costenoble, R., Heinemann, M., Hucka, M., Le Novere, N., Li, P., Liebermeister, W., Mo, M. L., Oliveira, A. P., Petranovic, D., Pettifer, S., Simeonidis, E., Smallbone, K., Spasic, I., Weichart, D., Brent, R., Broomhead, D. S., Westerhoff, H. V., Kirdar, B., Penttila, M., Klipp, E., Palsson, B. O., Sauer, U., Oliver, S. G., Mendes, P., Nielsen, J., Kell, D. B. (2008). "A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology." Nat Biotechnol 26:1155-1160.18846089
  • Cherest, H., Thomas, D., Surdin-Kerjan, Y. (2000). "Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae." J Biol Chem 275:14056-14063.10799479
  • McNeil, J. B., Bognar, A. L., Pearlman, R. E. (1996). "In vivo analysis of folate coenzymes and their compartmentation in Saccharomyces cerevisiae." Genetics 142:371-381.8852837
  • Suliman, H. S., Sawyer, G. M., Appling, D. R., Robertus, J. D. (2005). "Purification and properties of cobalamin-independent methionine synthase from Candida albicans and Saccharomyces cerevisiae." Arch Biochem Biophys 441:56-63.16083849
  • Briza, P., Kalchhauser, H., Pittenauer, E., Allmaier, G., Breitenbach, M. (1996). "N,N'-Bisformyl dityrosine is an in vivo precursor of the yeast ascospore wall." Eur J Biochem 239:124-131.8706696
Synthesis Reference:Not Available
External Links:
ResourceLink
CHEBI ID20506
HMDB IDHMDB01846
Pubchem Compound ID91443
Kegg IDC00101
ChemSpider ID82572
FOODB IDFDB031192
WikipediaTetrahydrofolic_acid
BioCyc IDTHF

Enzymes

Protein Details
1. Phosphoribosylglycinamide formyltransferase
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:
ADE8
Uniprot ID:
P04161
Molecular weight:
23540.0
Reactions
10-formyltetrahydrofolate + N(1)-(5-phospho-D-ribosyl)glycinamide → tetrahydrofolate + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide.
Protein Details
2. Serine hydroxymethyltransferase, cytosolic
General function:
Involved in catalytic activity
Specific function:
Interconversion of serine and glycine
Gene Name:
SHM2
Uniprot ID:
P37291
Molecular weight:
52218.0
Reactions
5,10-methylenetetrahydrofolate + glycine + H(2)O → tetrahydrofolate + L-serine.
Protein Details
3. Serine hydroxymethyltransferase, mitochondrial
General function:
Involved in catalytic activity
Specific function:
Interconversion of serine and glycine
Gene Name:
SHM1
Uniprot ID:
P37292
Molecular weight:
53686.0
Reactions
5,10-methylenetetrahydrofolate + glycine + H(2)O → tetrahydrofolate + L-serine.
Protein Details
4. Dihydrolipoyl dehydrogenase, mitochondrial
General function:
Involved in oxidoreductase activity
Specific function:
Lipoamide dehydrogenase is a component of the alpha- ketoacid dehydrogenase complexes. This includes the pyruvate dehydrogenase complex, which catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). Acts also as component of the glycine cleavage system (glycine decarboxylase complex), which catalyzes the degradation of glycine
Gene Name:
LPD1
Uniprot ID:
P09624
Molecular weight:
54009.69922
Reactions
Protein N(6)-(dihydrolipoyl)lysine + NAD(+) → protein N(6)-(lipoyl)lysine + NADH.
Protein Details
5. Dihydrofolate reductase
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:
DFR1
Uniprot ID:
P07807
Molecular weight:
24260.80078
Reactions
5,6,7,8-tetrahydrofolate + NADP(+) → 7,8-dihydrofolate + NADPH.
Protein Details
6. C-1-tetrahydrofolate synthase, mitochondrial
General function:
Involved in formate-tetrahydrofolate ligase activity
Specific function:
5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH
Gene Name:
MIS1
Uniprot ID:
P09440
Molecular weight:
106216.0
Reactions
5,10-methylenetetrahydrofolate + NADP(+) → 5,10-methenyltetrahydrofolate + NADPH.
5,10-methenyltetrahydrofolate + H(2)O → 10-formyltetrahydrofolate.
ATP + formate + tetrahydrofolate → ADP + phosphate + 10-formyltetrahydrofolate.
Protein Details
7. Bifunctional purine biosynthesis protein ADE17
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:
ADE17
Uniprot ID:
P38009
Molecular weight:
65262.60156
Reactions
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.
Protein Details
8. Bifunctional purine biosynthesis protein ADE16
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:
ADE16
Uniprot ID:
P54113
Molecular weight:
65281.80078
Reactions
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.
Protein Details
9. Methionyl-tRNA formyltransferase, mitochondrial
General function:
Involved in methionyl-tRNA formyltransferase activity
Specific function:
Formylates methionyl-tRNA in mitochondria
Gene Name:
FMT1
Uniprot ID:
P32785
Molecular weight:
44616.19922
Reactions
10-formyltetrahydrofolate + L-methionyl-tRNA(fMet) + H(2)O → tetrahydrofolate + N-formylmethionyl-tRNA(fMet).
Protein Details
10. C-1-tetrahydrofolate synthase, cytoplasmic
General function:
Involved in formate-tetrahydrofolate ligase activity
Specific function:
5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH
Gene Name:
ADE3
Uniprot ID:
P07245
Molecular weight:
102204.0
Reactions
5,10-methylenetetrahydrofolate + NADP(+) → 5,10-methenyltetrahydrofolate + NADPH.
5,10-methenyltetrahydrofolate + H(2)O → 10-formyltetrahydrofolate.
ATP + formate + tetrahydrofolate → ADP + phosphate + 10-formyltetrahydrofolate.
Protein Details
11. 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase
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:
MET6
Uniprot ID:
P05694
Molecular weight:
85859.20313
Reactions
5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine → tetrahydropteroyltri-L-glutamate + L-methionine.
Protein Details
12. 3-methyl-2-oxobutanoate hydroxymethyltransferase
General function:
Involved in 3-methyl-2-oxobutanoate hydroxymethyltransferase activity
Specific function:
5,10-methylenetetrahydrofolate + 3-methyl-2- oxobutanoate + H(2)O = tetrahydrofolate + 2-dehydropantoate
Gene Name:
ECM31
Uniprot ID:
P38122
Molecular weight:
34464.69922
Reactions
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H(2)O → tetrahydrofolate + 2-dehydropantoate.
Protein Details
13. Spore wall maturation protein DIT1
General function:
Secondary metabolites biosynthesis, transport and catabolism
Specific function:
Involved in spore wall maturation. Catalyzes a two step reaction that leads to the LL-dityrosine containing precursor of the spore wall
Gene Name:
DIT1
Uniprot ID:
P21623
Molecular weight:
61390.10156
Reactions
Protein Details
14. Folylpolyglutamate synthase
General function:
Coenzyme transport and metabolism
Specific function:
Conversion of folates to polyglutamate derivatives
Gene Name:
MET7
Uniprot ID:
Q08645
Molecular weight:
62150.89844
Reactions
ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate → ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).