Quantitative Analysis of NAD Synthesis-Breakdown Fluxes

被引：406

作者：

Liu, Ling ^{[1
,2
,3
]}

Su, Xiaoyang ^{[1
,4
]}

Quinn, William J., III ^{[5
,6
]}

Hui, Sheng ^{[1
]}

Krukenberg, Kristin ^{[7
,8
]}

Frederick, David W. ^{[5
,6
]}

Redpath, Philip ^{[9
]}

Zhan, Le ^{[10
]}

Chellappa, Karthikeyani ^{[5
,6
]}

White, Eileen ^{[10
]}

Migaud, Marie ^{[9
,11
]}

Mitchison, Timothy J. ^{[7
]}

Baur, Joseph A. ^{[5
,6
]}

Rabinowitz, Joshua D. ^{[1
,2
,3
]}

机构：

[1] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA

[2] Princeton Univ, Dept Chem, Princeton, NJ 08540 USA

[3] Univ Penn, Diabet Res Ctr, Philadelphia, PA 19104 USA

[4] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08904 USA

[5] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA

[6] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA

[7] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA

[8] Shire, Lexington, MA 02421 USA

[9] Queens Univ Belfast, Sch Pharm, Belfast BT9 7BL, Antrim, North Ireland

[10] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA

[11] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36604 USA

来源：

CELL METABOLISM | 2018年 / 27卷 / 05期

基金：

英国生物技术与生命科学研究理事会;

关键词：

NICOTINAMIDE ADENINE-DINUCLEOTIDE; POLY(ADP-RIBOSE) POLYMERASE-1; CELL-DEATH; ACID NICOTINAMIDE; METABOLIC FLUXES; SKELETAL-MUSCLE; BASE-EXCHANGE; BREAST-CANCER; MECHANISM; RIBOSIDE;

D O I：

10.1016/j.cmet.2018.03.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The redox cofactor nicotinamide adenine dinucleotide (NAD) plays a central role in metabolism and is a substrate for signaling enzymes including polyADP-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.

引用

页码：1067 / +

页数：19

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