Tetrahydrofolic acid

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Tetrahydrofolic acid
Tetrahydrofolic acid.svg
Tetrahydrofolic-acid-3D-spacefill.png
Names
IUPAC name
N-[4-({[(6Ξ)-2-Amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamic acid
Systematic IUPAC name
(2S)-2-[4-({[(6Ξ)-2-Amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzamido]pentanedioic acid
Identifiers
3D model (JSmol)
101189
ChEBI
ChemSpider
DrugBank
KEGG
MeSH 5,6,7,8-tetrahydrofolic+acid
PubChem CID
UNII
  • 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 Yes check.svgY
    Key: MSTNYGQPCMXVAQ-KIYNQFGBSA-N Yes check.svgY
  • 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
  • O=C(O)[C@@H](NC(=O)c1ccc(cc1)NCC3N/C2=C(/N/C(=N\C2=O)N)NC3)CCC(=O)O
Properties
C19H23N7O6
Molar mass 445.43 g/mol
Melting point 250 °C (482 °F; 523 K)
0.27 g/L
Acidity (pKa)3.51
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative.

Contents

Metabolism

Pathway of tetrahydrofolate and antimetabolites Pathway of tetrahydrofolate and antimetabolites.pdf
Pathway of tetrahydrofolate and antimetabolites

In humans, tetrahydrofolic acid 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.

Many bacteria produce tetrahydrofolic acid via dihydropteroate.[ citation needed ] 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. [2] [3] [4]

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. [5]

References

  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. Bibcode:2002PNAS...9913481R. doi: 10.1073/pnas.172501499 . ISSN   0027-8424. PMC   129699 . PMID   12359872.
  2. ↑ "Biochemistry: The One-Carbon Pool: Folate and B12 Metabolism". liveonearth.livejournal.com. 2008-02-23. Retrieved 2020-12-15.
  3. ↑ Yadav, Manish K.; Manoli, Nandini M.; Madhunapantula, SubbaRao V. (2016-10-25). Roemer, Klaus (ed.). "Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia". PLOS ONE. 11 (10): e0164559. Bibcode:2016PLoSO..1164559Y. doi: 10.1371/journal.pone.0164559 . ISSN   1932-6203. PMC   5079580 . PMID   27780269.
  4. ↑ Aslinia, F.; Mazza, J. J.; Yale, S. H. (2006-09-01). "Megaloblastic Anemia and Other Causes of Macrocytosis". Clinical Medicine & Research. 4 (3): 236–241. doi:10.3121/cmr.4.3.236. ISSN   1539-4182. PMC   1570488 . PMID   16988104.
  5. ↑ Dawson W, Maudsley DV, West GB (December 1965). "Histamine formation in guinea-pigs". J. Physiol. 181 (4): 801–9. doi:10.1113/jphysiol.1965.sp007798. PMC   1357684 . PMID   5881255.
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