Simplified scheme depicting intracellular metabolism of folates. THF indicates tetrahydrofolate; DHF, dihydrofolate; CH2-THF, methylene-THF; CH3-THF, methyl-THF; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; dTMP, deoxy thymidine monophosphate; dUMP, deoxy uridine monophosphate; TS, thymidylate synthase; MTHFR, methylenetetrahydrofolate reductase; MTHFD, methylenetetrahydrofolate dehydrogenase; MTR, methionine synthase; MTRR, methionine synthase reductase; SHMT, serine-hydroxymethyltransferase; DHFR, dihydrofolate reductase; RFC, reduced folate carrier; FR, folate receptors, and MTG-PG, methotrexate-polyglutamate. Food folate (CH3-THF) and MTX enter the cell by way of FR or the RFC.