期刊
CELL METABOLISM
卷 27, 期 5, 页码 1067-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2018.03.018
关键词
-
资金
- NIH [DP1DK113643, R01CA163591, R01DK098656, R01AG043483]
- University of Pennsylvania Diabetes Research Center [P30DK0s19525]
- Stand Up To Cancer-Pancreatic Cancer Dream Team Research Grant [SU2CAACR-DT-20-16]
- Rutgers Cancer Institute of New Jersey) [R01 CA130893, R01 CA188096, P30 CA72720]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/N001842/1]
- Biotechnology and Biological Sciences Research Council [BB/N001842/1] Funding Source: researchfish
- BBSRC [BB/N001842/1] Funding Source: UKRI
The redox cofactor nicotinamide adenine dinucleotide (NAD) plays a central role in metabolism and is a substrate for signaling enzymes including polyADP-ribose-polymerases (PARPs) and sirtuins. NAD concentration falls during aging, which has triggered intense interest in strategies to boost NAD levels. A limitation in understanding NAD metabolism has been reliance on concentration measurements. Here, we present isotope-tracer methods for NAD flux quantitation. In cell lines, NAD was made from nicotinamide and consumed largely by PARPs and sirtuins. In vivo, NAD was made from tryptophan selectively in the liver, which then excreted nicotinamide. NAD fluxes varied widely across tissues, with high flux in the small intestine and spleen and low flux in the skeletal muscle. Intravenous administration of nicotinamide riboside or mononucleotide delivered intact molecules to multiple tissues, but the same agents given orally were metabolized to nicotinamide in the liver. Thus, flux analysis can reveal tissue-specific NAD metabolism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据