Tetrahydrofolic acid

Not to be confused with Tetrahydrofuran.

Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative.

Tetrahydrofolic acid

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
CAS Number	135-16-0 Y
3D model (JSmol)	Interactive image
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 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
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 YN ?) Infobox references

Metabolism

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]

• 
  Dihydrofolic acid
• 
  5,10-Methylenetetrahydrofolic acid
• 
  10-Formyltetrahydrofolic acid