Key role of uridine kinase and uridine phosphorylase in the homeostatic regulation of purine and pyrimidine salvage in brain.

摘要: Uridine, the major circulating pyrimidine nucleoside, participating in regulation of a number physiological processes, is readily uptaken into mammalian cells. The balance between anabolism and catabolism intracellular uridine maintained by kinase, catalyzing first step UTP CTP salvage synthesis, phosphorylase, degradation to beta-alanine liver. In present study we report that two enzymes have an additional role homeostatic purine metabolism brain, which relies on synthesis nucleotides from preformed nucleosides nucleobases, rather than de novo simple precursors. experiments were performed rat brain extracts cultured human astrocytoma rationale reciprocal stands (i) inhibition exerted CTP, final products pathway, kinase (ii) widely accepted idea occurs at nucleoside level (mostly uridine), while 5-phosphoribosyl-1-pyrophosphate (PRPP)-mediated process, occurring nucleobase level. Thus, relatively low level, mainly anabolized nucleotides. On contrary, high levels channels towards phosphorolysis. ribose-1-phosphate then transformed PRPP, used for synthesis.