dUMP biosynthetic process

Definition

Target type: biologicalprocess

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

The dUMP biosynthetic process is a crucial step in the synthesis of deoxythymidine monophosphate (dTMP), a key component of DNA. This process involves the conversion of deoxyuridine monophosphate (dUMP) to dTMP through the action of the enzyme thymidylate synthase (TS).

The process starts with dUMP, a deoxyribonucleotide that lacks a methyl group at the 5-position of its pyrimidine ring. TS catalyzes the transfer of a methyl group from tetrahydrofolate (THF) to the 5-position of dUMP, converting it to dTMP.

The reaction proceeds in two main steps:

1. **Formation of a covalent intermediate:** TS binds to both dUMP and THF, forming a ternary complex. This complex facilitates the transfer of a one-carbon unit from THF to dUMP.
2. **Reduction and release of dihydrofolate:** The transferred one-carbon unit is reduced to a methyl group, generating dihydrofolate (DHF). DHF is released from the enzyme, and dTMP is produced.

The dUMP biosynthetic process is essential for DNA replication and repair. Deficiencies in this pathway can lead to severe health consequences, including impaired cell proliferation and DNA damage.

This pathway is also a target for several anticancer drugs. These drugs, known as thymidylate synthase inhibitors, block the activity of TS, thereby inhibiting DNA synthesis and cell proliferation in cancer cells.'
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