Cytidine deaminase
Cytidine Deaminase (CDA) is an enzyme that in humans is encoded by the CDA gene. This enzyme plays a crucial role in pyrimidine metabolism, specifically in the deamination of cytidine to uridine and deoxycytidine to deoxyuridine. Cytidine deaminase is part of the larger family of deaminase enzymes, which are involved in removing amine groups from molecules. The activity of this enzyme is essential for the salvage pathway of nucleotide synthesis, which is critical for DNA repair and replication in all living cells.
Function
Cytidine deaminase catalyzes the hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively. This reaction is important for the regulation of the intracellular concentration of nucleosides and for the maintenance of the nucleotide pool balance within the cell. By converting cytidine into uridine, this enzyme facilitates the recycling of nucleosides and plays a vital role in pyrimidine salvage pathways, which are crucial for nucleic acid synthesis in rapidly dividing cells.
Clinical Significance
The activity of cytidine deaminase has significant implications in medicine and pharmacology, particularly in the metabolism of certain chemotherapeutic agents. For example, the enzyme's ability to deaminate cytidine analogs used in chemotherapy, such as gemcitabine and cytarabine, affects the efficacy and toxicity of these drugs. High levels of cytidine deaminase activity in cancer cells can lead to resistance to these chemotherapeutic agents, making the enzyme a potential target for cancer therapy.
Furthermore, genetic variations in the CDA gene can influence the activity of the enzyme, affecting drug metabolism and leading to variability in drug response among individuals. This has implications for personalized medicine, as determining an individual's CDA genotype could help predict their response to cytidine analog-based chemotherapy.
Genetic Structure
The CDA gene is located on chromosome 1p36.3 in humans. It consists of several exons and introns that encode the cytidine deaminase protein. Mutations in the CDA gene have been associated with altered enzyme activity and have been studied in the context of drug metabolism and resistance to chemotherapy.
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Contributors: Prab R. Tumpati, MD