Catalyzes the hydrolytic deamination of cytosine to uracil. Is involved in the pyrimidine salvage pathway, which allows the cell to utilize cytosine for pyrimidine nucleotide synthesis. Is also able to catalyze deamination of isoguanine, a mutagenic oxidation product of adenine in DNA, and of isocytosine. To a lesser extent, also catalyzes the conversion of 5-fluorocytosine (5FC) to 5-fluorouracil (5FU); this activity allows the formation of a cytotoxic chemotherapeutic agent from a non-cytotoxic precursor. cytosine + H(+) + H2O = NH4(+) + uracil H(+) + H2O + isoguanine = NH4(+) + xanthine The purified enzyme contains a mixture of Fe(2+) and Zn(2+) bound in the active site, and a single equivalent of metal is required for full catalytic activity. After removal of the metal, the reconstitution of the enzyme with Fe(2+) gives the highest activity, followed by Mn(2+), and, to a much lesser extent, Co(2+) and Zn(2+). Fe(2+)-CDase is rapidly inactivated by H(2)O(2), whereas Mn(2+)-CDase, Co(2+)-CDase, and Zn(2+)-CDase are not inactivated by H(2)O(2). CDase is also inhibited by excess divalent cations (PubMed:8226944). Phosphonocytosine, a mimic of the tetrahedral reaction intermediate, inhibits the deamination of cytosine with a Ki of 52 nM (PubMed:21545144). kcat is 185 sec(-1) for the deamination of cytosine using Fe(2+) as cofactor, kcat is 92 sec(-1) using Mn(2+) as cofactor, kcat is 52 sec(-1) using Co(2+) as cofactor, and kcat is 32 sec(-1) using Zn(2+) as cofactor (PubMed:8226944). kcat is 165 sec(-1) for the deamination of cytosine and 75.6 sec(-1) for the deamination of 5-fluorocytosine (PubMed:15381761). kcat is 132 sec(-1) for the deamination of cytosine, 5.1 sec(-1) for the deamination of isocytosine, 5.6 sec(-1) for the deamination of creatinine and 2.3 sec(-1) for the hydrolysis of 3-oxauracil (PubMed:21545144). kcat is 45 sec(-1) for the deamination of cytosine and 49 sec(-1) for the deamination of isoguanine at pH 7.7 (PubMed:21604715). Activity is lost under pH 5 but not affected up to pH 10. Homohexamer. Cells lacking this gene have less than 1% of the isoguanine deaminase activity of the wild-type strain. Cytosine deaminase is being explored for use as a suicide gene for cancer gene therapy. The cytosine deaminase/5-fluorouracil combined therapy has been used successfully for a variety of animal tumor models and is currently under investigation for the treatment of human cancers. Belongs to the metallo-dependent hydrolases superfamily. Cytosine deaminase family. Extended N-terminus.