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methylenetetrahydrofolate mthf cofactor carbon metabolism formyl tetrahydrofolate thymidylate synthase homocysteine cycle folic acid mthfr mutation synthesis methionine vitamin b12 methyl thf supplement diastereoisomer pyrimidine biosynthesis biomodulator coenzyme cancer tumor enzyme 3d rendering chemical biochemistry biology biomolecule molecule molecular structural structure formula metabolite mechanism pathway biosynthetic precursor derivative bioprecursor metabolic