Thymidylate synthase and nucleic acids (TYMS/NA)

Thymidylate synthase (TYMS) is a pivotal enzyme in the folate metabolism pathway, responsible for the de novo synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) from 2'-deoxyuridine-5'-monophosphate (dUMP). This reaction is the sole intracellular source of thymidylate, making it a rate-limiting step essential for DNA replication and repair [1, 3]. Nucleic acids, including DNA and RNA, serve as both structural templates and functional targets for antimetabolite drugs. Chemotherapeutic agents such as 5-fluorouracil (5-FU) exert their cytotoxic effects through a dual mechanism: the irreversible inhibition of TYMS and the misincorporation of fraudulent fluorinated nucleotides into DNA and RNA [2, 4]. This combined action leads to "thymineless death," significant DNA damage, and the disruption of RNA processing and protein synthesis. Consequently, this target complex is a cornerstone in the treatment of various solid tumors, particularly colorectal, breast, and gastric cancers [2, 3].

Other names

TYMSThymidylate synthetaseTSDNARNADeoxyribonucleic acidRibonucleic acid

Irreversible inhibition of thymidylate synthase and fraudulent incorporation of nucleotide analogs into DNA and RNA