Cytidine deaminase (CDA) is an enzyme encoded by the CDA gene in humans. This enzyme plays a crucial role in the pyrimidine salvage pathway, which is essential for maintaining the cellular pyrimidine pool. The enzyme catalyzes the irreversible hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively .
Cytidine deaminase forms a homotetramer, meaning it consists of four identical subunits. This structure is vital for its function, as it allows the enzyme to efficiently catalyze the deamination process. The enzyme’s activity is dependent on zinc ions, which are required for its catalytic function .
Cytidine deaminase is involved in the pyrimidine salvage pathway, which recycles pyrimidine nucleosides for nucleotide synthesis. This pathway is crucial for maintaining the balance of nucleotides within the cell, which is essential for DNA and RNA synthesis. The enzyme’s activity ensures that cytidine and deoxycytidine are converted to uridine and deoxyuridine, preventing the accumulation of cytidine and maintaining the cellular nucleotide pool .
Mutations in the CDA gene can lead to decreased sensitivity to cytosine nucleoside analogs, such as cytosine arabinoside, which are used in the treatment of certain childhood leukemias. This resistance can impact the effectiveness of chemotherapy treatments, making it a significant area of study in cancer research .
Human recombinant cytidine deaminase is produced using recombinant DNA technology, which involves inserting the CDA gene into a suitable expression system, such as bacteria or yeast. This allows for the large-scale production of the enzyme for research and therapeutic purposes. Recombinant cytidine deaminase is used in various biochemical assays and studies to understand its function and role in nucleotide metabolism .
Cytidine deaminase is widely used in research to study nucleotide metabolism and the pyrimidine salvage pathway. It is also used in the development of gene-editing technologies, such as base editors, which utilize cytidine deaminases to introduce specific mutations in DNA. These technologies have significant potential for therapeutic applications, including the treatment of genetic disorders and cancers .