The Regulation of Brain Nucleoside Utilization
Piero L. Ipata and Francesco Balestri
Affiliation: Department of Biology, Unit of Biochemistry - University of Pisa, Via San Zeno 51, 56127 Pisa, Italy.
The homeostatic regulation of intracellular purine and pyrimidine pools has long been studied at the level of de
novo nucleotide synthesis. However, brain maintains the proper qualitative and quantitative nucleotide balance by salvaging
preformed nucleosides, imported from blood stream, rather than by de novo synthesis from simple precursors. The
main salvage enzymes are the nucleoside-kinases, catalyzing the ATP mediated phosphorylation of nucleosides in their
5’-position. Salvaged nucleoside-monophosphates are then either further phosphorylated, or converted back to nucleosides
by a set of 5’-nucleotidases. This poses the following problem: why are nucleosides produced from nucleosidemonophosphates,
to be converted back to the same compounds at the expense of ATP? As discussed in this article, the
quantitative and qualitative intracellular balance of brain purine and pyrimidine compounds is maintained i) by the intracellular
interplay between the rates of nucleoside-kinases and 5’-nucleotidases, ii) by the relative rates of the inward and
outward nucleoside transport through equilibrative and concentrative transport systems, iii) by the metabolic cross-talk between
extracellularly exported nucleoside-triphosphate breakdown and the intracellular process of nucleoside-triphosphate
Keywords: Substrate cycles, 5'-nucleotidases, cN-I, cN-II, cN-III, nucleoside recycling.
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