烟酰胺单核苷酸
NAD+激酶
烟酰胺
生物化学
辅因子
烟酰胺腺嘌呤二核苷酸
新陈代谢
烟酰胺
酶
烟酰胺磷酸核糖转移酶
化学
细胞外
生物
作者
Joanna Ratajczak,Magali Joffraud,Samuel A.J. Trammell,Rosa Ras,Núria Canela-Canela,Marie Boutant,Sameer S. Kulkarni,Marcelo Rodrigues Rodrigues,Philip Redpath,Marie E. Migaud,Johan Auwerx,Óscar Yanes,Charles Brenner,Carles Cantó
摘要
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.
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