2 Nucleoside and Nucleotide Kinases

Publisher Summary This chapter describes kinases that phosphorylate nucleosides to nucleoside monophosphates and that phosphorylate these nucleoside monophosphates to the nucleoside diphosphates. Nucleoside kinases catalyze a phosphoryl transfer from a nucleoside triphosphate to an R–OH acceptor, which is typically the 5′-hydroxyl group in the sugar moiety of the nucleoside. Nicotinamide-adenine dinucleotide kinase catalyzes phosphoryl transfer to an R–OH group, the 2′-hydroxyl of a ribose. Nucleoside monophosphokinases transfer phosphate from a nucleoside triphosphate to an acceptor. The enzymes within each group are subdivided in the usual manner on the basis of their specificity with regard to the phosphoryl acceptor. These specificities are not distinct, vary for enzymes from different sources, and even sometimes with the experimental conditions under which substrate specificity is examined. For inosine–guanosine kinase, the enzymic activity is distributed much less widely than is adenosine kinase or is much less active in most tissues, and a well-purified preparation catalyzing these phosphorylations has not been reported. Adenosine kinase may have some weak activity with at least inosine. A more difficult problem is that the nucleosides are readily broken down to the free bases, which can then react with phosphoribosyl pyrophosphate to form the nucleotides by this route rather than by direct phosphorylation.