Journal
PHARMACOLOGY & THERAPEUTICS
Volume 107, Issue 1, Pages 1-30Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2005.01.003
Keywords
nucleotidase; nucleoside metabolism; nucleoside analogues
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Funding
- NCI NIH HHS [R01 CA34085] Funding Source: Medline
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The 5'-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 riboand 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 5'-nucleotidases will be covered in this review, as will the evidence that these enzymes can mediate resistance to nucleoside analogues. (c) 2005 Published by Elsevier Inc.
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