BIOC 311 Lecture Notes - Lecture 26: Thymidylate Synthase, De Novo Synthesis, Neural Tube Defect
12 Feb 2020
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Dump comes through dephosphorylation of dutp (via dutpase) Dtmp is made via dump, with the help of folate. This is a target for drugs against cancer, bacteria and viruses. Needed for dna synthesis: thymidylate syn(the)t(h)ase. Reaction: dump + tetrahydrofolate dtmp + demethylated dihydrofolate. Essentially you steal the ch2 and another h from the folate. Thymidylate synthase is inhibited by fdump: dump with fluorine, you put it where the methyl would go and it blocks the enzyme via covalent modification (suicide inhibitor) The two n"s in red are the carriers. 3 carbon oxidation state carried in 5 forms: Carried as ch3: methanol, formaldehyde, formate. Know the name of the folate derivatives: regeneration of thf. Dhf is reduced back to thf via dihydrofolate reductase. The inhibitors look like dhf (particularly aminotreptin and methotrexate) Other drugs, such as sulfonamides, inhibit the de novo synthesis of folate: these are antibiotics, because humans take folate from food sources, competitive inhibitor, regeneration of n5,n10-methylene-thf.
