Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans

Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans

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Summary: 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 LADIES ACCESSORIES LUGGAGE 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 Girls Halloween Dress 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.