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The conversion of THF (the reduced form of folic acid) to 5,10-methylene-THF by 10-formyl-THF and 5,10-methenyl-THF is catalysed by the trifunctional enzyme methylene-THF dehydrogenase (MTHFD), which exhibits the activities of formyl-THF synthase, methenyl-THF cyclohydrolase, and methenyl-THF dehydrogenase [35]