Faculty Opinions recommendation of NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

NAD þ is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases.Supplementation with NAD þ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals.Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD þ synthesis.Using genetic gain-and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD þ synthesis from other NAD þ precursors, such as nicotinamide or nicotinic acid, is dispensable.Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD þ .Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD þ synthesis, explaining the overlapping metabolic effects observed with the two compounds.