English: Folate transport and C1 metabolism. A schematic is shown depicting cellular uptake by facilitative transport via RFC or PCFT or by endocytosis via FRα. Intracellular folates are metabolized to polyglutamate conjugates. Folate “monoglutamates” are transported into the mitochondria by SLC25A32. In the mitochondria, serine is catabolized by sequential SHMT2, MTHFD2/L, and MTHFD1L through which the C1 moiety from serine C3 is incorporated into formate, thus providing C1 units for cellular biosynthesis in the cytosol. Abbreviations are as follows: 10-CHO-THF, 10-formyl tetrahydrofolate; 5,10-me-THF, 5,10-methylene tetrahydrofolate; AICAR, 5-aminoimidazole-4-carboxamide; ALDH1L2, aldehyde dehydrogenase 1 family member L2; ATIC, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase; DHF, dihydrofolate; DHFR, dihydrofolate reductase; FAICAR, formyl 5-aminoimidazole-4-carboxamide ribonucleotide; fGAR, formyl glycinamide ribonucleotide; FPGS, folylpoly-γ-glutamate synthetase; GAR, glycinamide ribonucleotide; GARFTase, glycinamide ribonucleotide formyltransferase; GR, glutathione reductase; GS, glutathione synthetase; GSH, glutathione; MTFMT, methionyl tRNA formyltransferase; MTHFD1, methylenetetrahydrofolate dehydrogenase 1; MTHFD2(L), methylene tetrahydrofolate dehydrogenase 2(-like); MTHFR, methylenetetrahydrofolate reductase; MTR, methionine synthase; PCFT, proton-coupled folate transporter; PGs, polyglutamates; PRPP, phosphoribosyl pyrophosphate; RFC, reduced folate carrier; SAM, S-adenosylmethionine; SHMT1/2, serine hydroxymethyltransferase 1/2; THF, tetrahydrofolate; and TS, thymidylate synthase.