Nucleosides are overlooked fuels in central carbon metabolism.

Nucleosides and nucleic acids are abundant in our diet, but their nutritional value has been poorly investigated. Nucleosides maintain the viability of cells and organs when glucose is limited. Specific nucleoside phosphorylases, including uridine phosphorylase 1/2 (UPP1/2), thymidine phosphorylase (TYMP), and purine nucleoside phosphorylase (PNP), catalyze nucleoside cleavage and release of the ribose moiety, which can enter the glycolytic pathway, thus fueling central carbon metabolism. UPP1/2 integrate genetic and environmental signals to regulate uridine catabolism. Energy production from nucleosides has major implications for metabolism, immunity, and cancer. From our daily nutrition and synthesis within cells, nucleosides enter the bloodstream and circulate throughout the body and tissues. Nucleosides and nucleotides are classically viewed as precursors of nucleic acids, but recently they have emerged as a novel energy source for central carbon metabolism. Through catabolism by nucleoside phosphorylases, the ribose sugar group is released and can provide substrates for lower steps in glycolysis. In environments with limited glucose, such as at sites of infection or in the tumor microenvironment (TME), cells can use, and may even require, this alternative energy source. Here, we discuss the implications of these new findings in health and disease and speculate on the potential new roles of nucleosides and nucleic acids in energy metabolism. [ABSTRACT FROM AUTHOR]