烟酰胺的来源决定了它在培养细胞、小鼠和人类中的代谢命运。
Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans.
作者信息
Dutta Tumpa, Kapoor Nidhi, Mathew Meril, Chakraborty Suban S, Ward Nathan P, Prieto-Farigua Nicolas, Falzone Aimee, DeLany James P, Smith Steven R, Coen Paul M, DeNicola Gina M, Gardell Stephen J
机构信息
Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA.
Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA.
出版信息
Cell Rep. 2023 Mar 28;42(3):112218. doi: 10.1016/j.celrep.2023.112218. Epub 2023 Mar 9.
Metabolic routing of nicotinamide (NAM) to NAD or 1-methylnicotinamide (MeNAM) has impacts on human health and aging. NAM is imported by cells or liberated from NAD. The fate of H-NAM in cultured cells, mice, and humans was determined by stable isotope tracing. H-NAM is an NAD precursor via the salvage pathway in cultured A549 cells and human PBMCs and in A549 cell xenografts and PBMCs from H-NAM-dosed mice and humans, respectively. H-NAM is a MeNAM precursor in A549 cell cultures and xenografts, but not isolated PBMCs. NAM released from NAD is a poor MeNAM precursor. Additional A549 cell tracer studies yielded further mechanistic insight. NAMPT activators promote NAD synthesis and consumption. Surprisingly, NAM liberated from NAD in NAMPT activator-treated A549 cells is also routed toward MeNAM production. Metabolic fate mapping of the dual NAM sources across the translational spectrum (cells, mice, humans) illuminates a key regulatory node governing NAD and MeNAM synthesis.
烟酰胺（NAM）向烟酰胺腺嘌呤二核苷酸（NAD）或1-甲基烟酰胺（MeNAM）的代谢途径对人类健康和衰老有影响。NAM由细胞摄取或从NAD中释放出来。通过稳定同位素示踪法确定了H-NAM在培养细胞、小鼠和人类中的去向。在培养的A549细胞和人外周血单个核细胞（PBMC）中，以及在来自给予H-NAM的小鼠和人类的A549细胞异种移植物和PBMC中，H-NAM分别通过补救途径作为NAD的前体。在A549细胞培养物和异种移植物中，H-NAM是MeNAM的前体，但在分离的PBMC中不是。从NAD释放的NAM是一种较差的MeNAM前体。更多的A549细胞示踪研究提供了进一步的机制见解。烟酰胺磷酸核糖转移酶（NAMPT）激活剂促进NAD的合成和消耗。令人惊讶的是，在NAMPT激活剂处理的A549细胞中从NAD释放的NAM也会导向MeNAM的产生。跨翻译谱（细胞、小鼠、人类）对两种NAM来源的代谢命运图谱揭示了一个控制NAD和MeNAM合成的关键调节节点。
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