title: The human NAD metabolome: Functions, metabolism and compartmentalization.
abstract: The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD(+) and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools.
authors.affiliation: a Institute of Nanobiotechnologies, St. Petersburg State Polytechnical University , St. Petersburg , Russia .|b Institute of Cytology, Russian Academy of Sciences , St. Petersburg , Russia , and.
authors.forename: Andrey
authors.initials: A
authors.lastname: Nikiforov
authors.affiliation: a Institute of Nanobiotechnologies, St. Petersburg State Polytechnical University , St. Petersburg , Russia .
authors.forename: Veronika
authors.initials: V
authors.lastname: Kulikova
authors.affiliation: c Department of Molecular Biology , University of Bergen , Bergen , Norway.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D055442:Metabolome; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D015388:Organelles / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D009243:NAD
keywords: ADP-ribosylation; NAD biosynthesis; calcium signaling; extracellular NAD degradation; protein deacetylation; subcellular NAD pools
references.citation: FASEB J. 2001 Jan;15(1):10-12
references.pmid: 11099492
references.citation: Nature. 2014 Apr 10;508(7495):258-62
references.pmid: 24717514
references.citation: Cell Metab. 2014 Dec 2;20(6):1059-68
references.pmid: 25470550
references.citation: Neurobiol Aging. 2013 Jun;34(6):1581-8
references.pmid: 23312803
references.citation: Biochem J. 2003 Sep 1;374(Pt 2):329-35
references.pmid: 12790796
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14178-82
references.pmid: 11106374
references.citation: Biochem J. 2012 Apr 1;443(1):241-7
references.pmid: 22185573
references.citation: FASEB J. 2008 Mar;22(3):861-9
references.pmid: 17928361
references.citation: J Biol Chem. 1958 Aug;233(2):488-92
references.pmid: 13563526
references.citation: FEBS J. 2013 Aug;280(15):3519-29
references.pmid: 23639026
references.citation: Science. 2011 Jun 17;332(6036):1443-6
references.pmid: 21680843
references.citation: Diabetologia. 2005 Sep;48(9):1776-83
references.pmid: 16059715
references.citation: Trends Endocrinol Metab. 2012 Sep;23(9):420-8
references.pmid: 22819213
references.citation: Nat Struct Mol Biol. 2013 Apr;20(4):508-14
references.pmid: 23474712
references.citation: Annu Rev Nutr. 2008;28:115-30
references.pmid: 18429699
references.citation: Biochem Soc Trans. 2007 Feb;35(Pt 1):109-14
references.pmid: 17233614
references.citation: J Biol Chem. 1995 Jan 27;270(4):1529-34
references.pmid: 7829480
references.citation: J Cell Sci. 2004 Nov 1;117(Pt 23):5633-42
references.pmid: 15509867
references.citation: J Biol Chem. 1989 Jan 25;264(3):1608-15
references.pmid: 2912976
references.citation: J Biol Chem. 1997 May 2;272(18):11895-901
references.pmid: 9115250
references.citation: Science. 2011 Nov 11;334(6057):806-9
references.pmid: 22076378
references.citation: Nat Rev Mol Cell Biol. 2012 Apr;13(4):225-38
references.pmid: 22395773
references.citation: Annu Rev Biochem. 2005;74:739-89
references.pmid: 15952902
references.citation: Clin Cancer Res. 2005 Sep 15;11(18):6550-7
references.pmid: 16166432
references.citation: Nature. 2008 Mar 27;452(7186):492-6
references.pmid: 18337721
references.citation: Mol Cell Biol. 2012 Dec;32(24):5022-34
references.pmid: 23045395
references.citation: Nat Chem Biol. 2011 Dec;7(12):885-7
references.pmid: 22002720
references.citation: PLoS One. 2014;9(6):e98972
references.pmid: 24905194
references.citation: Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18964-9
references.pmid: 24191052
references.citation: Cell Calcium. 2015 Jul;58(1):27-47
references.pmid: 25449298
references.citation: J Biol Chem. 1958 Aug;233(2):493-500
references.pmid: 13563527
references.citation: Cell. 2007 Sep 21;130(6):1095-107
references.pmid: 17889652
references.citation: Front Biosci. 2008;13:3046-82
references.pmid: 17981777
references.citation: Cell. 2007 May 4;129(3):473-84
references.pmid: 17482543
references.citation: Cell Metab. 2011 Oct 5;14(4):528-36
references.pmid: 21982712
references.citation: Curr Med Chem. 2009;16(11):1372-90
references.pmid: 19355893
references.citation: Eur J Biochem. 1989 Dec 8;186(1-2):205-11
references.pmid: 2513184
references.citation: Biol Chem. 2010 Jan;391(1):1-8
references.pmid: 19804362
references.citation: Cell Calcium. 2010 Jun;47(6):480-90
references.pmid: 20621760
references.citation: Biochemistry. 2008 Oct 21;47(42):11086-96
references.pmid: 18823127
references.citation: J Biol Chem. 1951 Mar;189(1):203-16
references.pmid: 14832232
references.citation: Cell Biochem Biophys. 2013;67(3):865-73
references.pmid: 23532607
references.citation: Trends Biochem Sci. 2010 Apr;35(4):208-19
references.pmid: 20106667
references.citation: EMBO J. 2013 May 2;32(9):1225-37
references.pmid: 23481255
references.citation: J Biol Chem. 2010 Oct 29;285(44):34106-14
references.pmid: 20724478
references.citation: Nat Struct Mol Biol. 2013 Apr;20(4):502-7
references.pmid: 23474714
references.citation: Trends Biochem Sci. 2004 Mar;29(3):111-8
references.pmid: 15003268
references.citation: J Biol Chem. 2004 Nov 19;279(47):48893-903
references.pmid: 15364945
references.citation: Cell Metab. 2007 Nov;6(5):363-75
references.pmid: 17983582
references.citation: Cell Mol Life Sci. 2006 Jan;63(2):123-43
references.pmid: 16378245
references.citation: J Biol Chem. 2004 Jun 25;279(26):27017-21
references.pmid: 15090536
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15026-31
references.pmid: 17015823
references.citation: Annu Rev Biochem. 2006;75:295-332
references.pmid: 16756494
references.citation: J Biol Chem. 2002 Jun 14;277(24):22103-6
references.pmid: 11934891
references.citation: Nat Rev Neurosci. 2014 Jun;15(6):394-409
references.pmid: 24840802
references.citation: Nature. 2000 Feb 17;403(6771):795-800
references.pmid: 10693811
references.citation: J Biol Chem. 2006 Feb 3;281(5):2489-96
references.pmid: 16316998
references.citation: J Neurochem. 2001 Aug;78(3):646-57
references.pmid: 11483668
references.citation: J Biol Chem. 2005 Feb 18;280(7):5343-9
references.pmid: 15574424
references.citation: Biochim Biophys Acta. 2012 Sep;1822(9):1374-86
references.pmid: 22206997
references.citation: Eur J Biochem. 1997 Jan 15;243(1-2):408-14
references.pmid: 9030766
references.citation: Int J Biochem Cell Biol. 2000 Apr;32(4):391-5
references.pmid: 10762064
references.citation: Mol Cell Biol. 2012 Sep;32(18):3743-55
references.pmid: 22801369
references.citation: Mol Pharmacol. 2011 Dec;80(6):1136-46
references.pmid: 21917911
references.citation: Immunity. 2003 Oct;19(4):571-82
references.pmid: 14563321
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16359-64
references.pmid: 17913880
references.citation: Int J Exp Diabetes Res. 2002 Apr-Jun;3(2):79-96
references.pmid: 11991201
references.citation: Cell Metab. 2012 Jun 6;15(6):838-47
references.pmid: 22682224
references.citation: J Endocrinol Invest. 2004 Jul-Aug;27(7):695-707
references.pmid: 15505998
references.citation: Biochem J. 2012 Jan 1;441(1):131-41
references.pmid: 21933152
references.citation: J Biol Chem. 2006 Feb 24;281(8):4671-7
references.pmid: 16373343
references.citation: J Biol Chem. 2006 Oct 20;281(42):31419-29
references.pmid: 16926152
references.citation: Physiol Rev. 2013 Jul;93(3):1139-206
references.pmid: 23899562
references.citation: J Neurosci Res. 2007 Nov 15;85(15):3378-85
references.pmid: 17853438
references.citation: Biochem Mol Biol Int. 1996 Feb;38(2):297-306
references.pmid: 8850525
references.citation: Genes Cancer. 2013 Mar;4(3-4):148-63
references.pmid: 24020006
references.citation: Curr Top Med Chem. 2013;13(23):2907-17
references.pmid: 24171775
references.citation: Biochim Biophys Acta. 2015 Sep;1853(9):2095-103
references.pmid: 25447548
references.citation: Curr Biol. 2008 Oct 28;18(20):1612-8
references.pmid: 18951023
references.citation: J Biol Chem. 2013 Sep 6;288(36):25938-49
references.pmid: 23880765
references.citation: Pharm Res. 2007 Mar;24(3):575-84
references.pmid: 17245649
references.citation: Annu Rev Pathol. 2010;5:253-95
references.pmid: 20078221
references.citation: Trends Endocrinol Metab. 2009 Apr;20(3):130-8
references.pmid: 19109034
references.citation: Mol Microbiol. 2007 Oct;66(1):14-25
references.pmid: 17725566
references.citation: Arch Biochem Biophys. 2014 Dec 15;564:156-63
references.pmid: 25250980
references.citation: Cell. 2004 May 14;117(4):495-502
references.pmid: 15137942
references.citation: J Biol Chem. 2011 Jun 17;286(24):21110-7
references.pmid: 21498885
references.citation: J Biol Chem. 2012 Sep 14;287(38):31633-40
references.pmid: 22822066
references.citation: J Biol Chem. 1951 Dec;193(2):497-507
references.pmid: 14907738
references.citation: FEBS J. 2005 Sep;272(18):4576-89
references.pmid: 16156780
references.citation: Oncogene. 2008 Nov 6;27(52):6679-89
references.pmid: 18724390
references.citation: J Biol Chem. 1995 Feb 3;270(5):2152-7
references.pmid: 7836444
references.citation: Curr Med Chem. 2013;20(34):4205-16
references.pmid: 23992316
references.citation: Carcinogenesis. 2011 Feb;32(2):138-45
references.pmid: 21045016
references.citation: Mol Cell Biol. 2009 Nov;29(21):5872-88
references.pmid: 19703994
references.citation: J Biol Chem. 2006 Jan 20;281(3):1524-31
references.pmid: 16291748
references.citation: QJM. 2005 Mar;98(3):215-26
references.pmid: 15728403
references.citation: Genomics. 2005 May;85(5):591-9
references.pmid: 15820311
references.citation: J Biol Chem. 2008 Jun 13;283(24):16332-41
references.pmid: 18411268
references.citation: Biochim Biophys Acta. 2002 Jan 31;1594(1):127-35
references.pmid: 11825615
references.citation: Biochem J. 1987 Jul 1;245(1):263-7
references.pmid: 2822015
references.citation: Arch Biochem Biophys. 1993 Aug 15;305(1):147-52
references.pmid: 8393643
references.citation: Cell Mol Life Sci. 2004 Jan;61(1):19-34
references.pmid: 14704851
references.citation: Trends Biochem Sci. 2007 Jan;32(1):12-9
references.pmid: 17161604
references.citation: FASEB J. 1999 Feb;13(2):273-83
references.pmid: 9973315
references.citation: Mol Biol Cell. 2005 Oct;16(10):4623-35
references.pmid: 16079181
references.citation: FEBS J. 2013 Aug;280(15):3530-41
references.pmid: 23617329
references.citation: FEBS J. 2012 Apr;279(8):1356-65
references.pmid: 22248144
references.citation: Genes Dev. 2007 Apr 15;21(8):920-8
references.pmid: 17437997
references.citation: Front Biosci. 2008;13:6135-54
references.pmid: 18508649
references.citation: Nat Rev Cancer. 2012 Nov;12(11):741-52
references.pmid: 23018234
references.citation: PLoS One. 2009;4(4):e5090
references.pmid: 19352492
references.citation: J Biol Chem. 2009 Nov 6;284(45):31249-59
references.pmid: 19745225
references.citation: Nat Chem Biol. 2013 May;9(5):300-6
references.pmid: 23455543
references.citation: Mol Aspects Med. 2013 Dec;34(6):1046-65
references.pmid: 23290998
references.citation: Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R139-47
references.pmid: 15809266
references.citation: J Biol Chem. 2006 May 19;281(20):14057-65
references.pmid: 16565078
references.citation: Curr Med Chem. 2004 Apr;11(7):857-72
references.pmid: 15078170
references.citation: Cell Mol Life Sci. 2015 Mar;72(6):1209-25
references.pmid: 25292337
references.citation: Genes Dev. 1995 Dec 1;9(23):2888-902
references.pmid: 7498786
references.citation: Trends Endocrinol Metab. 2014 Mar;25(3):138-45
references.pmid: 24388149
references.citation: J Biol Chem. 2003 Jan 17;278(3):1794-801
references.pmid: 12427752
references.citation: J Biol Chem. 2011 Dec 30;286(52):44480-90
references.pmid: 22033928
references.citation: J Biol Chem. 2009 Dec 11;284(50):34861-9
references.pmid: 19846558
references.citation: J Biol Chem. 1994 May 20;269(20):14835-40
references.pmid: 8182091
references.citation: Histol Histopathol. 1999 Oct;14(4):1321-40
references.pmid: 10506947
references.citation: J Biol Chem. 2012 May 11;287(20):16088-102
references.pmid: 22433848
references.citation: Biochim Biophys Acta. 2015 Sep;1854(9):1132-7
references.pmid: 25534250
references.citation: Proc Natl Acad Sci U S A. 2000 May 23;97(11):5807-11
references.pmid: 10811920
references.citation: Endocr Rev. 2010 Apr;31(2):194-223
references.pmid: 20007326
references.citation: Can J Vet Res. 2003 Jul;67(3):229-31
references.pmid: 12889731
references.citation: Nature. 2011 Sep 29;477(7366):616-20
references.pmid: 21892188
references.citation: Cell. 2006 Sep 8;126(5):941-54
references.pmid: 16959573
references.citation: Sci Signal. 2012;5(241):ra67
references.pmid: 22969159
references.citation: Eur J Neurosci. 2012 Feb;35(3):423-35
references.pmid: 22276961
references.citation: Science. 2005 Jan 21;307(5708):426-30
references.pmid: 15604363
references.citation: Cell Mol Life Sci. 2010 Feb;67(3):433-43
references.pmid: 19902144
references.citation: FASEB J. 1998 Nov;12(14):1507-20
references.pmid: 9806760
references.citation: J Immunol. 2007 Jul 1;179(1):186-94
references.pmid: 17579037
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6658-63
references.pmid: 10841563
references.citation: J Biol Chem. 2009 Jan 2;284(1):158-64
references.pmid: 19001417
references.citation: Biosci Biotechnol Biochem. 2013;77(9):1888-93
references.pmid: 24018665
references.citation: Front Biosci. 2008;13:6716-29
references.pmid: 18508690
references.citation: J Biol Chem. 2002 May 24;277(21):18535-44
references.pmid: 11893743
references.citation: Stem Cells Dev. 2011 Jul;20(7):1183-98
references.pmid: 20964598
references.citation: J Biol Chem. 2011 Jan 28;286(4):2455-60
references.pmid: 21097500
references.citation: J Biol Chem. 2009 Jun 26;284(26):17668-76
references.pmid: 19411252
references.citation: J Biol Chem. 2008 Mar 7;283(10):6367-74
references.pmid: 18180302
references.citation: J Biol Chem. 2006 Jan 13;281(2):705-13
references.pmid: 16278211
references.citation: J Physiol. 2011 Apr 1;589(Pt 7):1515-25
references.pmid: 21135052
references.citation: BMC Biochem. 2003 May 7;4:4
references.pmid: 12735798
references.citation: Front Biosci (Landmark Ed). 2015;20:389-404
references.pmid: 25553457
references.citation: Cell Metab. 2014 Jun 3;19(6):1042-9
references.pmid: 24814483
references.citation: Biochem Pharmacol. 2009 May 15;77(10):1612-20
references.pmid: 19426698
references.citation: Am J Physiol Renal Physiol. 2006 Feb;290(2):F486-95
references.pmid: 16189287
references.citation: J Cell Biol. 2012 Aug 6;198(3):371-85
references.pmid: 22869598
references.citation: J Biol Chem. 2011 Jun 17;286(24):21767-78
references.pmid: 21504897
references.citation: J Biol Chem. 1998 Sep 11;273(37):23629-32
references.pmid: 9726963
references.citation: Comput Struct Biotechnol J. 2013 May 27;4:e201301012
references.pmid: 24688693
references.citation: J Biol Chem. 1958 Apr;231(2):727-40
references.pmid: 13539007
references.citation: Pharmacol Ther. 2005 Jul;107(1):1-30
references.pmid: 15963349
references.citation: J Biol Chem. 2011 Apr 22;286(16):14271-81
references.pmid: 21349851
references.citation: Mol Aspects Med. 2013 Apr-Jun;34(2-3):465-84
references.pmid: 23266187
references.citation: Nature. 2001 May 31;411(6837):595-9
references.pmid: 11385575
references.citation: PLoS Biol. 2007 Oct 2;5(10):e263
references.pmid: 17914902
references.citation: Mol Cell Biol. 1994 Feb;14(2):1431-7
references.pmid: 8289818
references.citation: Physiol Rev. 2008 Jul;88(3):841-86
references.pmid: 18626062
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16687-91
references.pmid: 17075046
references.citation: ACS Chem Biol. 2012 Mar 16;7(3):443-63
references.pmid: 22220966
references.citation: J Biol Chem. 1992 May 25;267(15):10481-8
references.pmid: 1375222
references.citation: EMBO Mol Med. 2014 Jun;6(6):721-31
references.pmid: 24711540