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Folic acid metabolism and 5-MTHF transport across the choroid plexus epithelium in the brain

Red arrows and red crosses indicate the alternative pathway induced by FRα deficiency. Blue arrows indicate effects of folinic acid treatment. Legend: 5MTHF: 5-methylenetetrahydrofolate; B6: vitamin B6; B12: vitamin B12; CSF: cerebrospinal fluid; DHRF: dihydrofolate reductase; FRα: folate receptor alpha; Gly: glycine; GSH: glutathione reduced states; GSSG: glutathione oxidized states; MS: methionine synthase; MTHFD: methylenetetrahydrofolate dehydrogenase; MTHFR: methylenetetrahydrofolate reductase; MTHFS: methylenetetrahydrofolate synthase; PC: phosphatidylcholine; PCFT: proton-coupled folate transporter; PI: phosphatidylinositol; RFC: reduced folate carrier; SAH: S-adenosyl homocysteine; SAM: S-adenosyl-methionine; Ser: Serine; SHMT: serine-hydroxy methyl transferase; SM: sphingomyelin. (Source: Mafi S, Laroche-Raynaud C, et al. Pharmacoresistant epilepsy in childhood: think of the cerebral folate deficiency, a treatable disease. Brain Sci 2020;10(11):762.) (Creative Commons Attribution 4.0 International license.)

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