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tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate

General Background 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 and play a role in histidine catabolism . 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) . Folates are modified by the addition of glutamate moieties conjugated one to another via a series of gamma-glutamyl links to form an oligo-gamma-glutamyl tail. The polyglutamylated forms are usually preferred by the enzymes that use folates since the turnover rate of those compounds is markedly increased . In addition, in eukaryotic cells the glutamylated forms of folate facilitate the retention of the vitamin within the cell and its subcellular compartments . : THF Tetrahydrofolate (tetrahydropteroylmonoglutamate, H4PteGlu1, THF) 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 : PWY-2201, and the number of conjugated glutamate residues, see : PWY-2161. About This Pathway While plants and many microorganisms can synthesize folate coenzymes by the de novo synthesis pathway (see : PWY-6612), 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 : METHYLENE-THF and :10-FORMYL-THF to : THF. 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 : 5-METHYL-THF and : 10-FORMYL-THF (formyl-H4PteGlun) . The polyglutamyl folates are hydrolyzed to monoglutamate forms by : HS06361-MONOMER, and metabolized 5-methyl-H4PteGlu1. More about that process is found at the pathway : PWY-2161B. Insufficient supply of the vitamin in vertebrates leads to anemia in adults, and has been shown to cause neural tube malformation in human embryos . 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 ).

from BIOCYC source record: HUMAN_PWY-6613
Type: pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
BSID:
547490

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