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Deoxycytidine kinase (dCK) is an enzyme which is encoded by the DCK gene in humans. [ 5 ] dCK predominantly phosphorylates deoxycytidine (dC) and converts dC into deoxycytidine monophosphate .
Deoxycytidine is a deoxyribonucleoside, a component of deoxyribonucleic acid. It is similar to the ribonucleoside cytidine , but with one hydroxyl group removed from the C2' position. Deoxycytidine can be phosphorylated at C5' of the deoxyribose by deoxycytidine kinase , converting it to deoxycytidine monophosphate (dCMP), a DNA precursor.
Thymidylate kinase can phosphorylate TMP into thymidine diphosphate, which nucleoside diphosphate kinase can phosphorylate into thymidine triphosphate. The nucleosides cytidine and deoxycytidine can be salvaged along the uracil pathway by cytidine deaminase, which converts them to uridine and deoxyuridine, respectively.
In mammalian cells, the phosphorylation of purine deoxyribonucleosides is mediated predominantly by two deoxyribonucleoside kinases, cytosolic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. The protein encoded by this gene is responsible for phosphorylation of purine deoxyribonucleosides in the mitochondrial matrix. In addition ...
Arabinoside, a commonly used chemotherapy for leukemia and lymphomas, is converted into cytosine arabinoside triphosphate by deoxycytidine kinase. Mutation of deoxycytidine kinase or loss of expression results in resistance to arabinoside. [2] Growth factor expression levels can also promote resistance to antineoplastic therapies. [2]
This family includes deoxycytidine kinase (cytosolic) as well as the two mitochondrial enzymes deoxyguanosine kinase and thymidine kinase 2 in humans. The base specificity is generally broader than for the TK-1 family. Non-TK1 family members are widespread and found in eukaryotes as well as prokaryotes.
Clofarabine can be administered intravenously or given orally. Clofarabine enters cells via hENT1, hENT2, and hCNT2, where upon it is phosphorylated by deoxycytidine kinase to generate clofarabine-5´-monophosphate. The rate-limiting step in clofarabine metabolism is clofarabine-5´-diphosphosphate.
Deoxycytidine monophosphate is a molecule of interest in treating genetic disorders such as thymidine kinase 2 (TK2) deficiency.In the case of TK2 deficiency, dCMP in conjunction with deoxythymidine monophosphate (dTMP) to bypass the deficiency in the TK2 enzyme. [2]