Folic acid, also called pteroylglutamic acid, consists of a pterin ring bonded via a methylene bridge to ρ-aminobenzoic acid which is conjugated by a peptide-like bond to L-glutamic acid. Although folic acid refers specifically to pteroylglutamic acid, it is used as a generic term along with folate and folacin, to refer to a number of compounds that have similar structures and the same vitamin action in humans. Most foods contain some folates, but green leafy plant foods are generally good sources of folates, along with legumes and liver. Cooking typically reduced the folic acid content of foods considerably. Deficiency of folate causes megaloblastic haematopoiesis (release of large immature red blood cells), which is clinically indistinguishable from vitamin B12 deficiency. Folate insufficiency can raise plasma homocysteine levels and increase the risk of cardiovascular disease. Folates in high doses cause no toxicity, but folate appears to have no pharmacological action.
Most folates in foods are conjugates of pteroylglutamic acid, with the number of glutamate residues varying up to nine. Such conjugates require the action of conjugase in the plant and animal tissue, or in the intestine of humans, to liberate monoglutamate forms. The liberated monoglutamates are then transported by an active process into the enterocytes. Within the enterocytes the folate monoglutamates are reduced to tetrahydrofolate (THF). These reduced monoglutamate forms are transported in the blood bound to specific carrier proteins and enter cells, where they are conjugated to polyglutamates to form functioning co-enzymes. Tetrahydrofolate accept 1-carbon units from various degradation pathways for amino acids in either its N5 or N10 position, or balanced between both to form a five-member ring. These 1‑carbom units are then used in synthetic pathways. Folate is used in the interconversion of serine and glycine, in methionine regeneration from homocysteine, deamination of histidine, and in purine and pyrimidine synthesis.
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