If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: folic acid salvage, folate salvage, THF salvage
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Folate Biosynthesis|
Pathway Summary from MetaCyc:
Tetrahydrofolate (vitamin B9) and its derivatives, commonly termed folates, are essential cofactors that facilitate the transfer of one-carbon units from donor molecules into important biosynthetic pathways leading to methionine, purine, and pyrimidine biosynthesis. Folates also mediate the interconversion of serine and glycine, play a role in histidine catabolism [Lucock00], and in plants are also involved in photorespiration, amino acid metabolism and chloroplastic protein biosynthesis [Hanson02] [Jabrin03].
Folates are abundant in green leaves, and folic acid was initially isolated from a large amount (four tons) of spinach leaves. The name folate is derived from the Latin folium (leaf) [Mitchell41].
Folates are modified by the addition of glutamate moieties conjugated one to another via a series of γ-glutamyl links to form an oligo-γ-glutamyl tail. The polyglutamylated forms are usually preferred by the enzymes that use folates since the turnover rate of those compounds is markedly increased [Cossins97, Scott00, Kirk94]. In addition, in eukaryotic cells the glutamylated forms of folate facilitate the retention of the vitamin within the cell and its subcellular compartments [Appling91].
tetrahydropteroyl mono-L-glutamate (H4PteGlu1) is merely the parent structure of this large family of coenzymes. Members of the family differ in the oxidation state of the pteridine ring, the character of the one-carbon substituent at the N5 and N10 positions (see folate transformations I), and the number of conjugated glutamate residues (see folate polyglutamylation).
About This Pathway
While plants and many microorganisms can synthesize folate coenzymes by the de novo synthesis pathway (see superpathway of tetrahydrofolate biosynthesis), many of them are also capable of salvaging folate from different varieties, such as the 5,10-methenyl form, or the 5- or 10-formyl forms. This pathway describes the conversion of pre-existing 5,10-methylene-tetrahydrofolate and N10-formyl-tetrahydrofolate to tetrahydrofolate.
As vertebrates are not able to synthesize folate in vivo, they are absolutely dependent on nutritional sources, making folate a vitamin. Food folates exist mainly as the polyglutamylated forms N5-methyl-tetrahydrofolate and N10-formyl-tetrahydrofolate (formyl-H4PteGlun) [Thien77]. The polyglutamyl folates are first hydrolyzed to monoglutamate forms by γ-glutamyl hydrolase, and subsequently metabolized into N5-methyl-tetrahydropteroyl mono-L-glutamate. More about that process is found at the pathway glutamate removal from folates.
Insufficient supply of the vitamin in vertebrates leads to anemia in adults, and has been shown to cause neural tube malformation in human embryos [Feinleib01]. In addition, folate defficiency has been linked to a number of other birth defects, several types of cancer, dementia, affective disorders, Down's syndrom, and serious conditions affecting pregnancy outcome (for a review, see [Lucock00]).
Superpathways: superpathway of tetrahydrofolate biosynthesis and salvage
Variants: 4-aminobenzoate biosynthesis , folate polyglutamylation , folate transformations I , folate transformations II , formylTHF biosynthesis I , superpathway of tetrahydrofolate biosynthesis , tetrahydrofolate biosynthesis
Pathway Evidence Glyph:
Feinleib01: Feinleib M, Beresford SA, Bowman BA, Mills JL, Rader JI, Selhub J, Yetley EA (2001). "Folate fortification for the prevention of birth defects: case study." Am J Epidemiol 154(12 Suppl);S60-9. PMID: 11744531
Jabrin03: Jabrin S, Ravanel S, Gambonnet B, Douce R, Rebeille F (2003). "One-carbon metabolism in plants. Regulation of tetrahydrofolate synthesis during germination and seedling development." Plant Physiol 131(3);1431-9. PMID: 12644692
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