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]
^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. PMC129699. PMID 12359872.
^"Biochemistry: The One-Carbon Pool: Folate and B12 Metabolism". liveonearth.livejournal.com. 2008-02-23. Retrieved 2020-12-15.
^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. PMC5079580. PMID 27780269.
^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. PMC1570488. PMID 16988104.
^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. PMC1357684. PMID 5881255.
tetrahydrofolic, acid, confused, with, tetrahydrofuran, thfa, tetrahydrofolate, folic, acid, derivative, names, iupac, name, amino, hexahydropteridin, methyl, amino, benzoyl, glutamic, acid, systematic, iupac, name, amino, hexahydropteridin, methyl, amino, ben. Not to be confused with Tetrahydrofuran Tetrahydrofolic acid THFA or tetrahydrofolate is a folic acid derivative Tetrahydrofolic acid Names IUPAC name N 4 63 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 63 2 Amino 4 oxo 1 4 5 6 7 8 hexahydropteridin 6 yl methyl amino benzamido pentanedioic acid Identifiers CAS Number 135 16 0 Y 3D model JSmol Interactive image 3DMet B04806 Beilstein Reference 101189 ChEBI CHEBI 20506 Y ChemSpider 82572 Y DrugBank DB00116 Y IUPHAR BPS 4675 KEGG C00101 Y MeSH 5 6 7 8 tetrahydrofolic acid PubChem CID 91443 UNII 43ZWB253H4 Y 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 YKey MSTNYGQPCMXVAQ KIYNQFGBSA N YInChI 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 s1Key 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 Melting point 250 C 482 F 523 K Solubility in water 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 N verify what is Y N Infobox references Contents 1 Metabolism 1 1 Human synthesis 1 2 Bacterial synthesis 2 Functions 3 References 4 External linksMetabolism editHuman synthesis edit 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 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 nbsp Pathway of tetrahydrofolate and antimetabolitesFunctions editTetrahydrofolic 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 nbsp Dihydrofolic acid nbsp 5 10 Methylenetetrahydrofolic acid nbsp 10 Formyltetrahydrofolic acidReferences edit 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 Biochemistry The One Carbon Pool Folate and B12 Metabolism liveonearth livejournal com 2008 02 23 Retrieved 2020 12 15 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 Aslinia F Mazza J J Yale S H 2006 09 01 Megaloblastic Anemia and Other Causes of Macrocytosis Clinical Medicine amp Research 4 3 236 241 doi 10 3121 cmr 4 3 236 ISSN 1539 4182 PMC 1570488 PMID 16988104 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 External links editTetrahydrofolate bound to proteins in the PDB Retrieved from https en wikipedia org w index php title Tetrahydrofolic acid amp oldid 1183539583, wikipedia, wiki, book, books, library,
