FIGURE 1

FIGURE 1

Folate-mediated one-carbon metabolism. (A) Structure of folate derivatives. (B) FOCM consists of multiple reactions and contributes to amino acid metabolism, nucleotide synthesis and SAM formation. The enzymes involved in FOCM include: FPGS, folylpolyglutamate synthase; GGH: γ-glutamylhydrolase; DHFR, dihydrofolate reductase, SHMT1, cytosolic serine hydroxymethyltransferase; SHMT2, mitochondrial SHMT; MTHFD1, cytosolic tri-functional enzyme, C1-THF-synthetase; MTHFD2/2L, mitochondrial bi-functional enzyme (5,10-methylene-THF dehydrogenase/5,10-methenyl-THF cyclohydrolase); MTHFD1L, mitochondrial 10-formy-THF synthetase; FDH, 10-formyltetrahydrofolate dehydrogenase; MTHFS, 5-formyltetrahydrofolate cyclo-ligase; MTR, 5-methyltetrahydrofolate-homocysteine methyltransferase; MAT, methionine adenosyltransferase; AHCY, adenosylhomocysteinase; MTHFR, 5,10-methylene-THF dehydrogenase; TS, thymidylate synthetase; GAR/AICAR TF, glycinamide ribonucleotide/aminoimidazole carboxamide ribonucleotide transformylase. T, folate transporters; MFT, mitochondrial folate transporter; the green area indicates the folate cycle, and yellow area indicates the methionine cycle.