Conversion of 5-fluorocytosine to 5-fluorouracil

The conversion of 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) is an enzymatic process mediated by cytosine deaminase. This conversion is exploited in gene-directed enzyme prodrug therapy (GDEPT), where tumor cells are engineered to express cytosine deaminase, which then converts the relatively nontoxic prodrug 5-FC into the potent antimetabolite chemotherapeutic agent 5-FU. This targeted approach aims to generate cytotoxic drug selectively within tumor tissue, minimizing systemic toxicity. The locally generated 5-FU inhibits thymidylate synthase and incorporates into RNA/DNA, disrupting nucleic acid metabolism and leading to cell death.

Enzymatic conversion of 5-FC to 5-FU, resulting in inhibition of thymidylate synthase and incorporation into RNA/DNA