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Nat Commun. 2016 Oct 11;7:13103. doi: 10.1038/ncomms13103.

NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

Author information

1
Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, Switzerland.
2
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
3
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
4
Group of Research on Omic Methodologies (GROM), Universitat Rovira i Virgili, Reus 43204, Spain.
5
Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, Spain.
6
School of Pharmacy, Queen's University Belfast, Belfast BT7 1NN, UK.
7
Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
8
Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid 28029, Spain.
9
Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona 43007, Spain.

Abstract

NAD+ 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+ 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+ synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD+ synthesis from other NAD+ 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+. Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD+ synthesis, explaining the overlapping metabolic effects observed with the two compounds.

PMID:
27725675
PMCID:
PMC5476803
DOI:
10.1038/ncomms13103
[Indexed for MEDLINE]
Free PMC Article

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