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Cytosine deaminase (CD) is an enzyme that catalyzes the hydrolytic deamination of cytosine to uracil and is notably absent in mammalian cells (UniProt: P05016) [1]. The yeast-derived version from Saccharomyces cerevisiae (yCD) is a primary component in Gene-Directed Enzyme Prodrug Therapy (GDEPT), where it serves as a suicide gene delivered to neoplastic tissues (PubMed: PMC3151111) [2]. Once expressed in target cells, yCD converts the non-toxic antifungal prodrug 5-fluorocytosine (5-FC) into the potent antimetabolite 5-fluorouracil (5-FU) (PubChem: CID 3366) [3]. This localized production of 5-FU creates a high concentration of the toxin within the tumor, leading to DNA damage and apoptosis while sparing healthy tissues from systemic chemotherapy exposure (PubMed: 25159255) [4]. The yCD/5-FC system has been extensively studied in clinical trials for various cancers, including brain and prostate tumors, often utilizing viral vectors for delivery (ClinicalTrials.gov: NCT01470794) [5].
The enzyme catalyzes the deamination of the prodrug 5-fluorocytosine (5-FC) into the active cytotoxic agent 5-fluorouracil (5-FU), which subsequently inhibits thymidylate synthase and incorporates into RNA/DNA to induce cell death (PubChem: CID 3366) [3].
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