Tetrahydrofolic acid

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Tetrahydrofolic acid
Skeletal formula of tetrahydrofolic acid
Space-filling model of the tetrahydrofolic acid molecule
IUPAC name
(2S)-2-{[4-({[(6R)-2-amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
135-16-0 N
ChEBI CHEBI:20506 YesY
ChemSpider 82572 YesY
DrugBank DB00116 YesY
Jmol 3D model Interactive image
KEGG C00101 YesY
MeSH 5,6,7,8-tetrahydrofolic+acid
PubChem 91443
Molar mass 445.43 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Tetrahydrofolic acid, or tetrahydrofolate, is a folic acid derivative.


Synthesis pathway of tetrahydrofolic acid (click to enlarge).

Human synthesis[edit]

It is produced from dihydrofolic acid by dihydrofolate reductase. This reaction is inhibited by methotrexate.[1]

It is converted into 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase.

Bacterial synthesis[edit]

Many bacteria use dihydropteroate synthetase to produce dihydropteroate, a molecule without function in humans. This makes it a useful target for sulfonamide antibiotics, which compete with the PABA precursor.

Pathway of tetrahydrofolate and antimetabolites


It is a cofactor in many reactions, especially in the metabolism of amino acids and nucleic acids. It acts as a donor of a group with one carbon atom. It gets this carbon atom by sequestering formaldehyde produced in other processes. A shortage in tetrahydrofolic acid (FH4) can cause megaloblastic anemia.

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.[2]


  1. ^ Rajagopalan, P. T. Ravi; Zhang, Zhiquan; McCourt, Lynn; Dwyer, Mary; Benkovic, Stephen J.; Hammes, Gordon G. (2002-10-15). "Interaction of dihydrofolate reductase with methotrexate: Ensemble and single-molecule kinetics". Proceedings of the National Academy of Sciences. 99 (21): 13481–13486. doi:10.1073/pnas.172501499. ISSN 0027-8424. PMC 129699free to read. PMID 12359872. 
  2. ^ Dawson W, Maudsley DV, West GB (December 1965). "Histamine formation in guinea-pigs". J. Physiol. (Lond.). 181 (4): 801–9. doi:10.1113/jphysiol.1965.sp007798. PMC 1357684free to read. PMID 5881255. 

External links[edit]