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Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans
- Source :
- Cell Reports; 20230101, Issue: Preprints
- Publication Year :
- 2023
-
Abstract
- 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 2H4-NAM in cultured cells, mice, and humans was determined by stable isotope tracing. 2H4-NAM is an NAD+precursor via the salvage pathway in cultured A549 cells and human PBMCs and in A549 cell xenografts and PBMCs from 2H4-NAM-dosed mice and humans, respectively. 2H4-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.
Details
- Language :
- English
- ISSN :
- 22111247
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Cell Reports
- Publication Type :
- Periodical
- Accession number :
- ejs62351792
- Full Text :
- https://doi.org/10.1016/j.celrep.2023.112218