Quantitative Analysis of NAD Synthesis-Breakdown Fluxes

Cell Metabolism

Volumn 27, Issue 5, 2018, Pages 1067-1080.e5

  Liu, Ling ^a,b   Su, Xiaoyang ^a,c   Quinn, William J ^d   Hui, Sheng ^a   Krukenberg, Kristin ^e,f   Frederick, David W ^d   Redpath, Philip ^g   Zhan, Le ^h   Chellappa, Karthikeyani ^d   White, Eileen ^h   Migaud, Marie ^g,i   Mitchison, Timothy J ^e   Baur, Joseph A ^d   Rabinowitz, Joshua D ^a,b  

^a PRINCETON UNIVERSITY   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f SHIRE   (United States)

^g QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^h RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

ⁱ UNIVERSITY OF SOUTH ALABAMA   (United States)

Author keywords

flux quantification; isotope tracers; mass spectrometry; mononucleotide; NAD; NADH; niacin; nicotinamide; redox cofactor; riboside

Indexed keywords

ADENOSINE DIPHOSPHATE RIBOSE; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE KINASE; NICOTINAMIDE RIBOSIDE; NICOTINAMIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; SIRTUIN; TRYPTOPHAN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL GROWTH; CONTROLLED STUDY; DNA DAMAGE; ENERGY METABOLISM; HUMAN; HUMAN CELL; ISOTOPE LABELING; ISOTOPE TRACING; LIVER CELL; METABOLIC FLUX ANALYSIS; MOUSE; NONHUMAN; NUCLEOTIDE METABOLISM; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; SKELETAL MUSCLE; SMALL INTESTINE; SPLEEN; TURNOVER TIME; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; FEMALE; HCT 116 CELL LINE; HEP-G2 CELL LINE; LIVER; METABOLISM;

ANIMALS; 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;

EID: 85045949864     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2018.03.018     Document Type: Article

References (65)

1. Antoniewicz, M.R., Kelleher, J.K., Stephanopoulos, G., Determination of confidence intervals of metabolic fluxes estimated from stable isotope measurements. Metab. Eng. 8 (2006), 324–337.
2. Beneke, S., Alvarez-Gonzalez, R., Bürkle, A., Comparative characterisation of poly(ADP-ribose) polymerase-1 from two mammalian species with different life span. Exp. Gerontol. 35 (2000), 989–1002.
3. Bogan, K.L., Brenner, C., Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu. Rev. Nutr. 28 (2008), 115–130.
4. Bonkowski, M.S., Sinclair, D.A., Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat. Rev. Mol. Cell Biol. 17 (2016), 679–690.
5. Buncel, E., Lee, C., Isotopes in Hydrogen Transfer Processes. 1976, Elsevier.
6. Camacho-Pereira, J., Tarragó, M.G., Chini, C.C.S., Nin, V., Escande, C., Warner, G.M., Puranik, A.S., Schoon, R.A., Reid, J.M., Galina, A., Chini, E.N., CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab. 23 (2016), 1127–1139.
7. Cantó, C., Houtkooper, R.H., Pirinen, E., Youn, D.Y., Oosterveer, M.H., Cen, Y., Fernandez-Marcos, P.J., Yamamoto, H., Andreux, P.A., Cettour-Rose, P., et al. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity. Cell Metab. 15 (2012), 838–847.
8. Chiang, S.H., Harrington, W.W., Luo, G., Milliken, N.O., Ulrich, J.C., Chen, J., Rajpal, D.K., Qian, Y., Carpenter, T., Murray, R., et al. Genetic ablation of CD38 protects against Western diet-induced exercise intolerance and metabolic inflexibility. PLoS One, 10, 2015, e0134927.
9. Chini, E.N., CD38 as a regulator of cellular NAD: a novel potential pharmacological target for metabolic conditions. Curr. Pharm. Des. 15 (2009), 57–63.
10. Chini, C.C.S., Guerrico, A.M., Nin, V., Camacho-Pereira, J., Escande, C., Barbosa, M.T., Chini, E.N., Targeting of NAD metabolism in pancreatic cancer cells: potential novel therapy for pancreatic tumors. Clin. Cancer Res 20 (2014), 120–130.
11. Chini, C., Tarrago, M., Chini, E., NAD and the aging process: role in life, death and everything in between. Mol. Cell Endocrinol. 455 (2017), 62–74.
12. Davar, D., Beumer, J.H., Hamieh, L., Tawbi, H., Role of PARP inhibitors in cancer biology and therapy. Curr. Med. Chem. 19 (2012), 3907–3921.
13. Fang, E.F., Scheibye-Knudsen, M., Brace, L.E., Kassahun, H., SenGupta, T., Nilsen, H., Mitchell, J.R., Croteau, D.L., Bohr, V.A., Defective mitophagy in XPA via PARP-1 hyperactivation and NAD+/SIRT1 reduction. Cell 157 (2014), 882–896.
14. Fang, E.F., Scheibye-Knudsen, M., Chua, K.F., Mattson, M.P., Croteau, D.L., Bohr, V.A., Nuclear DNA damage signalling to mitochondria in ageing. Nat. Rev. Mol. Cell Biol. 17 (2016), 308–321.
15. Fouquerel, E., Goellner, E.M., Yu, Z., Gagné, J.P., Barbi de Moura, M., Feinstein, T., Wheeler, D., Redpath, P., Li, J., Romero, G., et al. ARTD1/PARP1 negatively regulates glycolysis by inhibiting hexokinase 1 independent of NAD+ depletion. Cell Rep. 8 (2014), 1819–1831.
16. Frederick, D.W., Loro, E., Liu, L., Davila, A. Jr., Chellappa, K., Silverman, I.M., Quinn, W.J. 3rd, Gosai, S.J., Tichy, E.D., Davis, J.G., et al. Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab. 24 (2016), 269–282.
17. Gibson, B.A., Zhang, Y., Jiang, H., Hussey, K.M., Shrimp, J.H., Lin, H., Schwede, F., Yu, Y., Kraus, W.L., Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation. Science 353 (2016), 45–50.
18. Haigis, M.C., Sinclair, D.A., Mammalian sirtuins: biological insights and disease relevance. Annu. Rev. Pathol. 5 (2010), 253–295.
19. Hasmann, M., Schemainda, I., FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res. 63 (2003), 7436–7442.
20. Hassa, P.O., Haenni, S.S., Elser, M., Hottiger, M.O., Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?. Microbiol. Mol. Biol. Rev. 70 (2006), 789–829.
21. Hayaishi, O., Ijichi, H., Ichiyama, A., Studies on the biosynthesis of NAD by a direct method of tracing metabolism in vivo. Adv. Enzyme Regul. 5 (1967), 9–22.
22. He, L., Meng, S., Germain-Lee, E.L., Radovick, S., Wondisford, F.E., Potential biomarker of metformin action. J. Endocrinol. 221 (2014), 363–369.
23. Hillyard, D., Rechsteiner, M., Olivera, B., Pyridine nucleotide metabolism in mammalian cells in culture. J. Cell Physiol. 82 (1973), 165–179.
24. Hui, S., Ghergurovich, J.M., Morscher, R.J., Jang, C., Teng, X., Lu, W., Esparza, L.A., Reya, T., Le Zhan, Yanxiang Guo, J., et al. Glucose feeds the TCA cycle via circulating lactate. Nature 551 (2017), 115–118.
25. Ijichi, H., Ichiyama, A., Hayaishi, O., Studies on the biosynthesis of nicotinamide adenine dinucleotide. 3. Comparative in vivo studies on nicotinic acid, nicotinamide, and quinolinic acid as precursors of nicotinamide adenine dinucleotide. J. Biol. Chem. 241 (1966), 3701–3707.
26. Krukenberg, K.A., Jiang, R., Steen, J.A., Mitchison, T.J., Basal activity of a PARP1-NuA4 complex varies dramatically across cancer cell lines. Cell Rep 8 (2014), 1808–1818.
27. Langelier, M.F., Ruhl, D.D., Planck, J.L., Kraus, W.L., Pascal, J.M., The Zn3 domain of human poly(ADP-ribose) polymerase-1 (PARP-1) functions in both DNA-dependent poly(ADP-ribose) synthesis activity and chromatin compaction. J. Biol. Chem. 285 (2010), 18877–18887.
28. Liu, L., Shah, S., Fan, J., Park, J.O., Wellen, K.E., Rabinowitz, J.D., Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage. Nat. Chem. Biol. 12 (2016), 345–352.
29. Malavasi, F., Deaglio, S., Funaro, A., Ferrero, E., Horenstein, A.L., Ortolan, E., Vaisitti, T., Aydin, S., Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol. Rev. 88 (2008), 841–886.
30. Menear, K.A., Adcock, C., Boulter, R., Cockcroft, X.L., Copsey, L., Cranston, A., Dillon, K.J., Drzewiecki, J., Garman, S., Gomez, S., et al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl] -2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J. Med. Chem. 51 (2008), 6581–6591.
31. Mori, V., Amici, A., Mazzola, F., Di Stefano, M., Conforti, L., Magni, G., Ruggieri, S., Raffaelli, N., Orsomando, G., Metabolic profiling of alternative NAD biosynthetic routes in mouse tissues. PLoS One 9 (2014), 1–27.
32. National Research Council, Recommended Dietary Allowances. Tenth Edition, 1989, National Academy Press.
33. Nikiforov, A., Dolle, C., Niere, M., Ziegler, M., Pathways and subcellular compartmentation of NAD biosynthesis in human cells from entry of extracellular precursors to mitochondrial NAD generation. J. Biol. Chem. 286 (2011), 21767–21778.
34. Ohashi, K., Kawai, S., Murata, K., Identification and characterization of a human mitochondrial NAD kinase. Nat. Commun. 3 (2012), 1248–1249.
35. Pirinen, E., Canto, C., Jo, Y.S., Morato, L., Zhang, H., Menzies, K.J., Williams, E.G., Mouchiroud, L., Moullan, N., Hagberg, C., et al. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab. 19 (2014), 1034–1041.
36. Pollak, N., Dölle, C., Ziegler, M., The power to reduce: pyridine nucleotides – small molecules with a multitude of functions. Biochem. J. 402 (2007), 205–218.
37. Powanda, M.C., Wannemacher, R.W. Jr., Evidence for a linear correlation between the level of dietary tryptophan and hepatic NAD concentration and for a systematic variation in tissue NAD concentration in the mouse and the rat. J. Nutr. 100 (1970), 1471–1478.
38. Ratajczak, J., Joffraud, M., Trammell, S.A., Ras, R., Canela, N., Boutant, M., Kulkarni, S.S., Rodrigues, M., Redpath, P., Migaud, M.E., et al. NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nat. Commun., 7, 2016, 13103.
39. Rechsteiner, M., Hillyard, D., Olivera, B.M., Magnitude and significance of NAD turnover in human cell line D98/AH2. Nature 259 (1976), 695–696.
40. Rechsteiner, M., Hillyard, D., Olivera, B.M., Turnover at nicotinamide adenine dinucleotide in cultures of human cells. J. Cell Physiol. 88 (1976), 207–217.
41. Revollo, J.R., Korner, A., Mills, K.F., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R.R., et al. Nampt/PBEF/visfatin regulates insulin secretion in β cells as a systemic NAD biosynthetic enzyme. Cell Metab. 6 (2007), 363–375.
42. Rouleau, M., Patel, A., Hendzel, M.J., Kaufmann, S.H., Poirier, G.G., PARP inhibition: PARP1 and beyond. Nat. Rev. Cancer 10 (2010), 293–301.
43. Ryu, D., Zhang, H., Ropelle, E.R., Sorrentino, V., Mazala, D.A., Mouchiroud, L., Marshall, P.L., Campbell, M.D., Ali, A.S., Knowels, G.M., et al. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci. Transl. Med., 8, 2016, 361ra139.
44. Sahar, S., Nin, V., Barbosa, M.T., Chini, E.N., Sassone-Corsi, P., Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation. Aging (Albany, NY) 3 (2011), 794–802.
45. Sauve, A.A., Schramm, V.L., Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry. Biochemistry 42 (2003), 9249–9256.
46. Sauve, A.A., Munshi, C., Lee, H.C., Schramm, V.L., The reaction mechanism for CD38. A single intermediate is responsible for cyclization, hydrolysis, and base-exchange chemistries. Biochemistry 37 (1998), 13239–13249.
47. Schreiber, V., Dantzer, F., Ame, J.C., de Murcia, G., Poly(ADP-ribose): novel functions for an old molecule. Nat. Rev. Mol. Cell Biol. 7 (2006), 517–528.
48. Soetaert, K., Petzoldt, T., Setzer, R.W., Package deSolve: solving initial value differential equations in R. J. Stat. Softw. 33 (2010), 1–25.
49. Su, X., Lu, W., Rabinowitz, J.D., Metabolite spectral accuracy on orbitraps. Anal. Chem. 89 (2017), 5940–5948.
50. Trammell, S.A., Brenner, C., Targeted, LCMS-based metabolomics for quantitative measurement of NAD(+) metabolites. Comput. Struct. Biotechnol. J., 4, 2013, e201301012.
51. Trammell, S.A., Schmidt, M.S., Weidemann, B.J., Redpath, P., Jaksch, F., Dellinger, R.W., Li, Z., Abel, E.D., Migaud, M.E., Brenner, C., Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat. Commun., 7, 2016, 12948.
52. van de Ven, R.A.H., Santos, D., Haigis, M.C., Mitochondrial sirtuins and molecular mechanisms of aging. Trends Mol. Med. 23 (2017), 320–331.
53. Virág, L., Robaszkiewicz, A., Rodriguez-Vargas, J.M., Oliver, F.J., Poly(ADP-ribose) signaling in cell death. Mol. Aspects Med. 34 (2013), 1153–1167.
54. Wang, J., Zhai, Q., Chen, Y., Lin, E., Gu, W., McBurney, M.W., He, Z., A local mechanism mediates NAD-dependent protection of axon degeneration. J. Cell Biol. 170 (2005), 349–355.
55. Wang, J., Kim, T.H., Ahn, M.Y., Lee, J., Jung, J.H., Choi, W.S., Lee, B.M., Yoon, K.S., Yoon, S., Kim, H.S., Sirtinol, a class III HDAC inhibitor, induces apoptotic and autophagic cell death in MCF-7 human breast cancer cells. Int. J. Oncol. 41 (2012), 1101–1109.
56. Wang, T.T.Y., Schoene, N.W., Kim, E.K., Kim, Y.S., Pleiotropic effects of the sirtuin inhibitor sirtinol involves concentration-dependent modulation of multiple nuclear receptor-mediated pathways in androgen-responsive prostate cancer cell LNCaP. Mol. Carcinog 52 (2013), 676–685.
57. Wang, G., Han, T., Nijhawan, D., Theodoropoulos, P., Naidoo, J., Yadavalli, S., Mirzaei, H., Pieper, A.A., Ready, J.M., McKnight, S.L., P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell 158 (2014), 1324–1334.
58. Xiao, Y., Elkins, K., Durieux, J.K., Lee, L., Oeh, J., Yang, L.X., Liang, X., DelNagro, C., Tremayne, J., Kwong, M., et al. Dependence of tumor cell lines and patient-derived tumors on the NAD salvage pathway renders them sensitive to NAMPT inhibition with GNE-618. Neoplasia 15 (2013), 1151–1160.
59. Yang, Y., Sauve, A.A., NAD+ metabolism: bioenergetics, signaling and manipulation for therapy. Biochim. Biophys. Acta 1864 (2016), 1787–1800.
60. Yuan, J., Bennett, B.D., Rabinowitz, J.D., Kinetic flux profiling for quantitation of cellular metabolic fluxes. Nat. Protoc. 3 (2008), 1328–1340.
61. Yuan, J., Doucette, C.D., Fowler, W.U., Feng, X.J., Piazza, M., Rabitz, H.A., Wingreen, N.S., Rabinowitz, J.D., Metabolomics-driven quantitative analysis of ammonia assimilation in E. coli. Mol. Syst. Biol., 5, 2009, 302.
62. Zerp, S.F., Vens, C., Floot, B., Verheij, M., van Triest, B., NAD+ depletion by APO866 in combination with radiation in a prostate cancer model, results from an in vitro and in vivo study. Radiother. Oncol. 11 (2014), 348–354.
63. Zhao, Y.J., Zhu, W.J., Wang, X.W., Zhang, L.H., Lee, H.C., Determinants of the membrane orientation of a calcium signaling enzyme CD38. Biochim. Biophys. Acta 1853 (2015), 2095–2103.
64. Zhou, W., Ni, T.K., Wronski, A., Glass, B., Skibinski, A., Beck, A., Kuperwasser, C., The SIRT2 deacetylase stabilizes slug to control malignancy of basal-like breast cancer. Cell Rep. 17 (2016), 1302–1317.
65. Zong, W.X., Ditsworth, D., Bauer, D.E., Wang, Z.Q., Thompson, C.B., Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 18 (2004), 1272–1282.