Metabolism

Folic acid occurs within the diet mainly as a polyglutamate compound. The latter is digested by the enzyme pteroyl polyglutamate hydrolase on the small intestine brush border into dihydro- and tetrahydrofolates. These substrates are kept in a reduced state by the presence of ascorbic acid.

Folate metabolites are absorbed into enterocytes by two key means:

• at physiological concentrations, by an active transport mechanism; the specific transporter is also used by the drug methotrexate
• at supraphysiological concentrations, by passive diffusion; this is the route taken by the majority of folate supplements

Cobalamin within cells is important for producing the metabolite tetrahydrofolate. Tetrahydrofolate is the metabolically active form of folate.