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

Tumpa Dutta; Nidhi Kapoor; Meril Mathew; Suban S. Chakraborty; Nathan P. Ward; Nicolas Prieto-Farigua; Aimee Falzone; James P. DeLany; Steven R. Smith; Paul M. Coen; Gina M. DeNicola; Stephen J. Gardell

Cell Reports (Mar 2023)

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

Tumpa Dutta,
Nidhi Kapoor,
Meril Mathew,
Suban S. Chakraborty,
Nathan P. Ward,
Nicolas Prieto-Farigua,
Aimee Falzone,
James P. DeLany,
Steven R. Smith,
Paul M. Coen,
Gina M. DeNicola,
Stephen J. Gardell

Affiliations

Tumpa Dutta: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA; Corresponding author
Nidhi Kapoor: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA
Meril Mathew: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA
Suban S. Chakraborty: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA
Nathan P. Ward: Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Nicolas Prieto-Farigua: Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Aimee Falzone: Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
James P. DeLany: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA
Steven R. Smith: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA
Paul M. Coen: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA
Gina M. DeNicola: Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Stephen J. Gardell: Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112218

Abstract

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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 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.

CP: Metabolism

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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