dTMP biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of dTMP, deoxyribosylthymine monophosphate (2'-deoxyribosylthymine 5'-phosphate). [ISBN:0198506732]

The biosynthesis of dTMP (deoxythymidine monophosphate) is a crucial step in DNA replication, ensuring the correct incorporation of thymine bases into the newly synthesized DNA strands. The process starts with the conversion of dUMP (deoxyuridine monophosphate) to dTMP, catalyzed by the enzyme thymidylate synthase (TS). This reaction involves a one-carbon unit transfer from tetrahydrofolate (THF) to dUMP, forming dTMP and dihydrofolate (DHF). THF acts as a carrier of one-carbon units, and its reduced form, dihydrofolate (DHF), is required for the reaction. The enzyme TS utilizes a unique catalytic mechanism, involving a covalent intermediate with dUMP, facilitating the transfer of the one-carbon unit from THF. This process requires the presence of methylenetetrahydrofolate reductase (MTHFR), which converts dihydrofolate back to tetrahydrofolate, allowing the cycle to continue. The dTMP produced is then incorporated into DNA by DNA polymerase, replacing dUMP with dTMP in the growing DNA strand. The dTMP biosynthesis pathway is a critical target for anticancer drugs, as inhibiting TS can effectively prevent DNA replication and cell growth. Several drugs, like methotrexate and 5-fluorouracil, act by inhibiting different steps in this pathway. These drugs disrupt the supply of dTMP, halting cell proliferation and demonstrating the importance of dTMP biosynthesis in maintaining cellular function.'
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Proteins (5)

Compounds (26)