定量分析 NAD 合成-分解通量。
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.
机构信息
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA; Department of Chemistry, Princeton University, Princeton, NJ 08540, USA; Diabetes Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA; Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08904, USA.
出版信息
Cell Metab. 2018 May 1;27(5):1067-1080.e5. doi: 10.1016/j.cmet.2018.03.018.
The redox cofactor nicotinamide adenine dinucleotide (NAD) plays a central role in metabolism and is a substrate for signaling enzymes including poly-ADP-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.
氧化还原辅助因子烟酰胺腺嘌呤二核苷酸 (NAD) 在新陈代谢中起着核心作用，是包括多聚 ADP-核糖聚合酶 (PARPs) 和沉默调节蛋白在内的信号酶的底物。随着年龄的增长，NAD 浓度下降，这引发了人们对提高 NAD 水平的策略的浓厚兴趣。对 NAD 代谢的理解受到对浓度测量的依赖的限制。在这里，我们提出了用于 NAD 通量定量的同位素示踪方法。在细胞系中，NAD 是由烟酰胺合成的，主要被 PARPs 和沉默调节蛋白消耗。在体内，NAD 是从色氨酸有选择地在肝脏中合成的，然后肝脏排泄烟酰胺。NAD 通量在组织之间差异很大，小肠和脾脏的通量高，骨骼肌的通量低。烟酰胺核糖苷或单核苷酸的静脉内给药将完整的分子输送到多个组织，但口服给予的相同试剂在肝脏中代谢为烟酰胺。因此，通量分析可以揭示组织特异性的 NAD 代谢。
Zotero 插件