Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.

TitleQuantitative Analysis of NAD Synthesis-Breakdown Fluxes.
Publication TypeJournal Article
Year of Publication2018
AuthorsLiu, L, Su, X, Quinn, WJ, Hui, S, Krukenberg, K, Frederick, DW, Redpath, P, Zhan, L, Chellappa, K, White, E, Migaud, M, Mitchison, TJ, Baur, JA, Rabinowitz, JD
JournalCell Metab
Volume27
Issue5
Pagination1067-1080.e5
Date Published2018 May 01
ISSN1932-7420
KeywordsAnimals, Female, HCT116 Cells, Hep G2 Cells, Humans, Intestine, Small, Liver, Mice, Mice, Inbred C57BL, Muscle, Skeletal, NAD, Niacinamide, Poly(ADP-ribose) Polymerases, Sirtuins, Spleen, Tryptophan
Abstract

<p>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.</p>

DOI10.1016/j.cmet.2018.03.018
Alternate JournalCell Metab.
PubMed ID29685734
PubMed Central IDPMC5932087
Grant ListR01 DK098656 / DK / NIDDK NIH HHS / United States
DP1 DK113643 / DK / NIDDK NIH HHS / United States
P30 CA072720 / CA / NCI NIH HHS / United States
R01 GM039565 / GM / NIGMS NIH HHS / United States
R01 CA163591 / CA / NCI NIH HHS / United States
R01 GM023928 / GM / NIGMS NIH HHS / United States
BB/N001842/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 CA188096 / CA / NCI NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
R01 CA130893 / CA / NCI NIH HHS / United States
R01 AG043483 / AG / NIA NIH HHS / United States