Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9015881 | Pharmacology & Therapeutics | 2005 | 30 Pages |
Abstract
The 5â²-nucleotidases are a family of enzymes that catalyze the dephosphorylation of nucleoside monophosphates and regulate cellular nucleotide and nucleoside levels. While the nucleoside kinases responsible for the initial phosphorylation of salvaged nucleosides have been well studied, many of the catabolic nucleotidases have only recently been cloned and characterized. Aside from maintaining balanced ribo- and deoxyribonucleotide pools, substrate cycles that are formed with kinase and nucleotidase activities are also likely to regulate the activation of nucleoside analogues, a class of anticancer and antiviral agents that rely on the nucleoside kinases for phosphorylation to their active forms. Both clinical and in vitro studies suggest that an increase in nucleotidase activity can inhibit nucleoside analogue activation and result in drug resistance. The physiological role of the 5â²-nucleotidases will be covered in this review, as will the evidence that these enzymes can mediate resistance to nucleoside analogues.
Keywords
CLLPRPPcN-IIdNTPTK2DGKCDNAZTdFdCFdUMPAMPCPIMPDHinosine monophosphate dehydrogenaseMDNDNCdNMPS-adenosylhomocysteineNDPKHGPRT2,3-BPGSAH3′-azido-2′,3′-dideoxythymidineAZTMPdCKAZT monophosphateNTParaCTPdNDPDFSCDAPNPDDI5-fluorodeoxyuridine monophosphatedFdCMPAMLTK11-β-d-arabinofuranosylcytosine2′,3′-dideoxyinosine2′,3′-dideoxycytidine2-chloro-2′-deoxyadenosine2,3-bisphosphoglycerate5′-NT5′-Nucleotidase5-phosphoribosyl 1-pyrophosphatecAMPcyclic 3′,5′-adenosine monophosphateddCMitochondrial DNAadenosine deaminaseadenosine kinaseNucleoside analoguesEcto-5′-nucleotidaseDisease free survivaloverall survivaltumor necrosis factor-αThymidylate kinaseThymidine phosphorylaseThymidine kinase 1Thymidine kinase 2AraCdeoxyribonucleoside triphosphatedeoxycytidine kinaseNucleoside diphosphate kinaseDeoxyguanosine kinasemtDNARibonucleotide reductaseribonucleoside triphosphatethymidylate synthaseTNF-αacute myeloid leukemiaAcute lymphoblastic leukemiaChronic lymphoblastic leukemiaNucleoside MetabolismwildtypeNucleotidaseALLADAPurine nucleoside phosphorylase
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Authors
Sally Anne Hunsucker, Beverly S. Mitchell, Jozef Spychala,