5-Fluorouracil thymine nucleotide synthesis

The treatment of cancer frequently involves drugs that interfere with DNA synthesis. For example, 5-fluorouracil (5-FU) prevents the conversion of dUMP to dTMP, reducing the level of thymine nucleotides required for DNA synthesis. Methotrexate prevents formation of tetrahy-drofolate from its more oxidized precursors. As a result, the formation of both thymine for DNA synthesis and the purines for DNA and RNA synthesis is inhibited. 

B. 5-Fluorouracil prevents conversion of dUMP to dTMP. DNA synthesis is inhibited because of a lack of thymine nucleotides, so this compound is used to treat cancer. 

Colin Tuma is being treated with 5-fluorouracil (5-FU), a pyrimidine base similar to uracil and thymine. 5-FU inhibits the synthesis of the thymine nucleotides required for DNA replication. Thymine is normally produced by a reaction catalyzed by thymidylate synthase, an enzyme that converts deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). 5-FU is converted in the body to F-dUMP, which binds tightly to thymidylate synthase in a transition state complex and inhibits the reaction (recall that thymine is 5-methyl uracil). Thus, thymine nucleotides cannot be generated for DNA synthesis, and the rate of cell proliferation decreases. 

Fluorouracil (5-FU) undergoes metabolism to form 5-fluoro-2 -deoxyuridine 5 -phosphate (5-dUMP). This metabolite forms a covalently bound ternary complex with thymidylate synthase and its coenzyme A-methylenetetrahydrofolate. The synthesis of thymine nucleotides is blocked, and a thymineless death of cells results. The answer is (E). 

Fluorouracil produces a nucleotide that binds to thymidylate synthetase and prevents the conversion of dUMP to dTMP. This inhibition of the synthesis of thymine prevents DNA synthesis and thus affects the proliferation of cells. 

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