What reaction does the enzyme thymidylate synthase Catalyse?
The enzyme thymidylate synthase (TSase), an important chemotherapeutic drug target, catalyzes the formation of 2′-deoxythymidine-5′-monophosphate (dTMP), a precursor of one of the DNA building blocks.
What are the products of thymidylate synthase reaction?
Thymidylate synthase (TS) (EC 2.1. 1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA.
What is thymidylate synthesis?
Thymidylate synthesis occurs at a greater rate during DNA replication when cells are in S-phase of the cell cycle. De novo thymidylate biosynthesis is impaired by folate or vitamin B12 deficiency. Impaired de novo thymidylate biosynthesis causes uracil misincorporation into DNA and DNA instability.
What is the coenzyme for thymidylate synthase?
The methylation of the uracil moiety (present in RNA) to 5-methyl uracil (thymine, present in DNA) requires participation of a folic acid coenzyme, N5, N10-methylenetetrahydrofolate as a methyl donor. The functioning of thymidylate synthetase is coupled with the activity of DHF reductase.
Is thymidylate synthase required for RNA synthesis?
Thymidylate synthase is required for the synthesis of DNA. Folic acid can be synthesized by bacteria, but not animals. Drugs that inhibit H2 folate reductase, or thymidylate synthase, are effective anticancer agents.
Which is a potent inhibitor of thymidylate synthase?
The antipyrimidine drug, 5-fluorouracil (5-FU), as its active metabolite, FdUMP, is a potent inhibitor of thymidylate synthase (TS), and this is generally considered to be its primary mechanism of action (Pratt et al., 1994).
What is the mechanism of action of 5-fluorouracil?
5-Fluorouracil (5-FU) can activate p53 by more than one mechanism: incorporation of fluorouridine triphosphate (FUTP) into RNA, incorporation of fluorodeoxyuridine triphosphate (FdUTP) into DNA and inhibition of thymidylate synthase (TS) by fluorodeoxyuridine monophosphate (FdUMP) with resultant DNA damage.