Metabolic Regulation of Uridine in the Brain

The importance of nucleoside metabolism in brain followed the recognition that i) adult nervous system maintains its nucleotide pools in the proper qualitative and quantitative balance by salvaging preformed purine and pyrimidine rings, rather than by synthesizing nucleosides de novo from simple precursors, ii) adenosine, a purine nucleoside, acts as an extracellular signal, and exerts its protective effects by interacting with plasmamembrane bound purinergic G-protein coupled P2X receptors. More recently uridine, a pyrimidine nucleoside, has received considerable attention. Most of the uridine content of brain is supplied by its uptake from the plasma. An increasing body of evidence suggests that uridine exerts its function intracellularly in three distinct ways. It is phosphorylated to UTP, a pyrimidine nucleotide acting as a precursors for RNA and DNA synthesis, and as an extracellular neurotrophic signal. In combination with the ω-3 fatty acid decosahexaenoic acid and choline, uridine accelerates formation of synaptic membrane, being an obligatory precursor for CDP-choline synthesis. Finally, uridine can preserve the ATP pool via the conversion of its ribose-1-phosphate moiety into energetic intermediates of glycolysis. This article summarizes our present knowledge on uridine metabolism in the brain, with special emphasis on the mechanisms maintaining its intracellular homeostasis and on the cross talk between intracellular and extracellular uridine metabolism.