Simplified scheme depicting intracellular metabolism of folates. For clarity reasons, the reaction catalysed by methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1) is not shown; MTHFD1 converts CH2-THF in 3 steps to THF and provides formyl-THF (CHO-THF) for purine synthesis. 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; MS, methionine synthase; MTRR, methionine synthase reductase; SHMT, serine-hydroxymethyltransferase; DHFR, dihydrofolate reductase; RFC, reduced folate carrier; MTX-PG, methotrexate-polyglutamate; and NADP, nicotinamide adenine dinucleotide.
