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MethyleneTHF generated by SHMT is the one-carbon donor for the TYMS catalyzed conversion of dUMP to dTMP generating dihydrofolate (DHF).
TS catalyzes the conversion of dUMP into dTMP using 5,10-MTHF.
The substrate for MTHFR, 5,10-methylene-tetrahydrofolate (THF) is used for conversion of dUMP to dTMP by the enzyme thymidylate synthase (TS).
Methylene-THF, which is generated by SHMT, acts as a one-carbon donor for the TYMS-catalyzed conversion of dUMP to thymidylate, generating dihydrofolate.
In the absence of tdk, cells exclusively rely on tetrahydrofolate dependent conversion of dUMP to dTMP, which is inhibited during TMP treatment.
Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis.
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Another widespread folate-dependent metabolic step is the conversion of dTMP to dUMP, catalyzed by thymidylate synthase (ThyA, EC 2.1.1.45).
Many enzymes are involved in folate metabolism, among which, thymidylate synthase (TYMS) catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), using the 5, 10-methylenetetrahydrofolate as a methyl donor [ 13].
Thymidylate synthase is essential for de novo DNA synthesis, by catalyzing the conversion of deoxy-uridine monophosphate (dUMP) to deoxy-thymidine monophosphate (dTMP).
In a deoA- mutant, the cells lack the ability to degrade deoxyuridine and this may lead to the increased accumulation of dUMP and dUTP in the cells, possibly due to the conversion of the accumulated deoxyuridine to dUMP via thymidine kinase [ 49].
R90 also hydrogen bonds to the C4 oxygen of dUMP.
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