Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases

Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monoph osphates are converted to their corresponding diphosphate form. These enzym es play an important role in the synthesis of nucleotides that are required for a variety of cellular metabolic processes, as well as for RNA and DNA synthesis. Human tissues contain a thymidylate kinase, a uridylate-cytidyla te kinase, five isozymes of adenylate kinase, and several guanylate kinases . Nucleoside monophosphate kinases are also required for the pharmacologica l activation of therapeutic nucleoside and nucleotide analogs. This overvie w is focused on the substrate specificity, tissue distribution, and subcell ular location of the mammalian monophosphate kinases and their role in the activation of nucleoside and nucleotide analogs. (C) 2000 Elsevier Science Inc. All rights reserved.