Tetrahydrofolic acid
{{distinguish|Tetrahydrofuran}}
{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 470604221
| ImageFile = Tetrahydrofolic acid.svg
| ImageClass= skin-invert-image
| ImageSize = 260px
| ImageAlt = Skeletal formula of tetrahydrofolic acid
| ImageFile1 = Tetrahydrofolic-acid-3D-spacefill.png
| ImageSize1 = 250
| ImageAlt1 = Space-filling model of the tetrahydrofolic acid molecule
| IUPACName = N-[4-({[(6Ξ)-2-Amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamic acid
| SystematicName = (2S)-2-[4-({[(6Ξ)-2-Amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzamido]pentanedioic acid
| OtherNames =
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4675
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 82572
| InChI = 1/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
| InChIKey = MSTNYGQPCMXVAQ-KIYNQFGBBC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MSTNYGQPCMXVAQ-KIYNQFGBSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 135-16-0
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 43ZWB253H4
| PubChem = 91443
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00116
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 20506
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00101
| 3DMet = B04806
| Beilstein = 101189
| SMILES = O=C(O)[C@@H](NC(=O)c1ccc(cc1)NCC3N/C2=C(/N/C(=N\C2=O)N)NC3)CCC(=O)O
| MeSHName = 5,6,7,8-tetrahydrofolic+acid
}}
|Section2={{Chembox Properties
| Formula = {{chem2|C19H23N7O6}}
| MolarMass = 445.43 g/mol
| Appearance =
| Density =
| MeltingPtC = 250
| BoilingPt =
| pKa = 3.51
| Solubility = 0.27 g/L
}}
|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}
Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative.
Metabolism
File:Pathway of tetrahydrofolate and antimetabolites.pdf
In humans, tetrahydrofolic acid is produced from dihydrofolic acid by dihydrofolate reductase. This reaction is inhibited by methotrexate.{{Cite journal|last1=Rajagopalan|first1=P. T. Ravi|last2=Zhang|first2=Zhiquan|last3=McCourt|first3=Lynn|last4=Dwyer|first4=Mary|last5=Benkovic|first5=Stephen J.|last6=Hammes|first6=Gordon G.|date=2002-10-15|title=Interaction of dihydrofolate reductase with methotrexate: Ensemble and single-molecule kinetics|journal=Proceedings of the National Academy of Sciences|language=en|volume=99|issue=21|pages=13481–13486|doi=10.1073/pnas.172501499|issn=0027-8424|pmc=129699|pmid=12359872|bibcode=2002PNAS...9913481R|doi-access=free}} It is converted into 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase.
Many bacteria produce tetrahydrofolic acid via dihydropteroate.{{cn|date=January 2025}} Humans lack the enzymes to do this, thus molecules that shut down these enzymes are effective antibacterial compounds. For example, sulfonamide antibiotics competitively binds the active site of dihydropteroate synthetase, excluding the binding of the dihydropteroate precuror, 4-aminobenzoic acid (PABA).
Functions
Tetrahydrofolic acid is a cofactor in many reactions, especially in the synthesis (or anabolism) of amino acids and nucleic acids. In addition, it serves as a carrier molecule for single-carbon moieties, that is, groups containing one carbon atom e.g. methyl, methylene, methenyl, formyl, or formimino. When combined with one such single-carbon moiety as in 10-formyltetrahydrofolate, it acts as a donor of a group with one carbon atom. Tetrahydrofolate gets this extra carbon atom by sequestering formaldehyde produced in other processes. These single-carbon moieties are important in the formation of precursors for DNA synthesis. A shortage in tetrahydrofolic acid (FH4) can cause megaloblastic anemia.{{Cite web|date=2008-02-23|title=Biochemistry: The One-Carbon Pool: Folate and B12 Metabolism |url=https://liveonearth.livejournal.com/260487.html|archive-url=|archive-date=|access-date=2020-12-15|website=liveonearth.livejournal.com}}{{Cite journal |last1=Yadav |first1=Manish K. |last2=Manoli |first2=Nandini M. |last3=Madhunapantula |first3=SubbaRao V. |date=2016-10-25 |editor-last=Roemer |editor-first=Klaus |title=Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia |journal=PLOS ONE |language=en |volume=11 |issue=10 |pages=e0164559 |doi=10.1371/journal.pone.0164559 |issn=1932-6203 |pmc=5079580 |pmid=27780269|bibcode=2016PLoSO..1164559Y |doi-access=free }}{{Cite journal |last1=Aslinia |first1=F. |last2=Mazza |first2=J. J. |last3=Yale |first3=S. H. |date=2006-09-01 |title=Megaloblastic Anemia and Other Causes of Macrocytosis |journal=Clinical Medicine & Research |language=en |volume=4 |issue=3 |pages=236–241 |doi=10.3121/cmr.4.3.236 |issn=1539-4182 |pmc=1570488 |pmid=16988104}}
Methotrexate acts on dihydrofolate reductase, like pyrimethamine or trimethoprim, as an inhibitor and thus reduces the amount of tetrahydrofolate made. This may result in megaloblastic anemia.
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.{{cite journal |vauthors=Dawson W, Maudsley DV, West GB |title=Histamine formation in guinea-pigs |journal=J. Physiol. |volume=181 |issue=4 |pages=801–9 |date=December 1965 |pmid=5881255 |pmc=1357684 |doi=10.1113/jphysiol.1965.sp007798 }}
Image:Dihydrofolic acid.svg|Dihydrofolic acid
Image:5,10-methylenetetrahydrofolic acid.svg|5,10-Methylenetetrahydrofolic acid
Image:10-formyl-tetrahydrofolic acid.svg|10-Formyltetrahydrofolic acid
References
{{reflist}}
External links
- [http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=THG Tetrahydrofolate bound to proteins] in the PDB
{{Enzyme cofactors}}
{{Authority control}}
{{DEFAULTSORT:Tetrahydrofolic Acid}}