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Definitions and folate forms

Folic acid (FA, pteroylmonoglutamic acid) is the synthetic and the most stable form of the vitamin. FA is fully oxidized and consists of a 2-amino-4-hydroxy-pteridine ring linked at the C-6 position to a p-aminobenzoic acid (pABA), and L-glutamic acid. FA is the preferred form that is used in dietary supplements and fortified foods, because of its taste- and odorless characteristics.

Naturally occurring folate forms consist of derivatives of 5,6,7,8-tetrahydropteroyl-γ-glutamate (THF) that are fully reduced at 5, 6, 7, and 8 positions of the pyrazine ring. Natural folate forms are polyglutamates, with five to eight glutamate residues prevailing in the mammalian cell (1). Folates exhibit a one-carbon unit at the N-5 and/or N-10 positions, which can be transferred by means of certain enzymes. Reduced folates function as acceptors and donors of “one-carbon units”. One hundred different vitamers have been detected in biological tissues (2). The chemical differences are strongly related to the bioavailability, cellular distribution, and functions of the different folate forms. In the folate dependent remethylation of homocysteine (Hcy), 5-methylTHF folate donates its methyl group to Hcy to give THF and methionine (3). Methionine is further converted to SAM by the ATP-dependent methionine adenosyltransferase. SAM is an important methyl donor for DNA, RNA, proteins, phospholipids, and neurotransmitters.



1.     Cook RJ. Folate metabolism. In: Carmel R, Jacobsen DW, eds. Homocysteine in Health and Disease. Cambridge, UK: Cambridge University Press, 2001:113-34.
2.     Krumdieck CL, Tamura T, Eto I. Synthesis and analysis of the pteroylpolyglutamates. Vitam Horm 1983;40:45-104.
3.     Shane B, Stokstad EL. Vitamin B12-folate interrelationships. Annu Rev Nutr 1985;5:115-41.