Thymidine Biosynthesis

Critical to the cell's process of replication is its ability to synthesize thymidine.5,6 This process involves several key enzymes including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyl transferase (SHMT) (Figure 1). The methylation of deoxyuridine 5'-monophosphate (dUMP) to produce deoxythymidine 5'-monophosphate (dTMP) is mediated by TS.7 The methyl group for dTMP is provided by N5,N10-methylene tetrahydrofolate (N5,N10-CH2-THF) through its conversion to 7,8-dihydrofolate (7,8-DHF). The 7,8-DHF must then

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