Tetrahydrofolic acid

Tetrahydrofolic acid
Names


IUPAC name (2S)-2-{[4-({[(6S)-2-amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
Identifiers
CAS Number	135-16-0^N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:20506^Y
ChemSpider	82572^Y
DrugBank	DB00116^Y
ECHA InfoCard	100.004.711
IUPHAR/BPS	4675
KEGG	C00101^Y
MeSH	5,6,7,8-tetrahydrofolic+acid
PubChem CID	91443
UNII	43ZWB253H4^N
InChI 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^Y Key: MSTNYGQPCMXVAQ-KIYNQFGBSA-N^Y 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 Key: MSTNYGQPCMXVAQ-KIYNQFGBBC
SMILES O=C(O)[C@@H](NC(=O)c1ccc(cc1)NCC3N/C2=C(/N/C(=N\C2=O)N)NC3)CCC(=O)O
Properties
Chemical formula	C₁₉H₂₃N₇O₆
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 ^YN ?)
Infobox references

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

Metabolism

Synthesis pathway of tetrahydrofolic acid (click to enlarge).

Human synthesis

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

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

Functions

Tetrahydrofolic acid is a cofactor in many reactions, especially in the synthesis (or anabolism) 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]

Enzyme cofactors

Active forms

vitamins	TPP / ThDP (B₁) FMN, FAD (B₂) NAD⁺, NADH, NADP⁺, NADPH (B₃) Coenzyme A (B₅) PLP / P5P (B₆) Biotin (B₇) THFA / H₄FA, DHFA / H₂FA, MTHF (B₉) AdoCbl, MeCbl (B₁₂) Ascorbic acid (C) Phylloquinone (K₁), Menaquinone (K₂) Coenzyme F420
non-vitamins	ATP CTP SAMe PAPS GSH Coenzyme B Cofactor F430 Coenzyme M Coenzyme Q Heme / Haem (A, B, C, O) Lipoic Acid Methanofuran Molybdopterin/Molybdenum cofactor PQQ THB / BH₄ THMPT / H₄MPT
minerals	Ca²⁺ Cu²⁺ Fe²⁺, Fe³⁺ Mg²⁺ Mn²⁺ Mo Ni²⁺ Zn²⁺

Base forms

vitamins: see vitamins

References

↑ 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. ISSN 0027-8424. PMC 129699 . PMID 12359872. doi:10.1073/pnas.172501499.
↑ Dawson W, Maudsley DV, West GB (December 1965). "Histamine formation in guinea-pigs". J. Physiol. (Lond.). 181 (4): 801–9. PMC 1357684 . PMID 5881255. doi:10.1113/jphysiol.1965.sp007798.

External links

Tetrahydrofolate bound to proteins in the PDB

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