The power to reduce: pyridine nucleotides—small molecules with a multitude of functions
Open accessAbstract
The pyridine nucleotides NAD and NADP play vital roles in metabolic conversions as signal transducers and in cellular defence systems. Both coenzymes participate as electron carriers in energy transduction and biosynthetic processes. Their oxidized forms, NAD+ and NADP+, have been identified as important elements of regulatory pathways. In particular, NAD+ serves as a substrate for ADP-ribosylation reactions and for the Sir2 family of NAD+-dependent protein deacetylases as well as a precursor of the calcium mobilizing molecule cADPr (cyclic ADP-ribose). The conversions of NADP+ into the 2′-phosphorylated form of cADPr or to its nicotinic acid derivative, NAADP, also result in the formation of potent intracellular calcium-signalling agents. Perhaps, the most critical function of NADP is in the maintenance of a pool of reducing equivalents which is essential to counteract oxidative damage and for other detoxifying reactions. It is well known that the NADPH/NADP+ ratio is usually kept high, in favour of the reduced form. Research within the past few years has revealed important insights into how the NADPH pool is generated and maintained in different subcellular compartments. Moreover, tremendous progress in the molecular characterization of NAD kinases has established these enzymes as vital factors for cell survival. In the present review, we summarize recent advances in the understanding of the biosynthesis and signalling functions of NAD(P) and highlight the new insights into the molecular mechanisms of NADPH generation and their roles in cell physiology.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NAD+ is used to synthesize NADP+, whose reduced form NADPH is involved in defense against oxidative stress.
“NAD + is used to synthesize NADP + , whose reduced form NADPH is involved in defense against oxidative stress (91).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Global analysis of protein expression in yeast
Ghaemmaghami, S., Huh, W.-K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., & Weissman, J. S. (2003) · Nature · doi:10.1038/nature02046 · Cited by 3,750 · see citing works
Genes required for mycobacterial growth defined by high density mutagenesis
Sassetti, C. M., Boyd, D. H., & Rubin, E. J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03425.x · Cited by 2,544 · see citing works
Berger, F., Lau, C., Dahlmann, M., & Ziegler, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508660200 · Cited by 508 · see citing works
Self-citationMitochondrial NADPH, transhydrogenase and disease
Rydström, J. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.03.010 · Cited by 256 · see citing works
Flagged first, then by citations
Research works printed but not linked: 15
- Sasiak, K. and Saunders, P. P. (1996) Purification and properties of a human nicotinamide ribonucleoside kinase. Arch. Biochem. Biophys. 333, 414-418
- Paone, G., Wada, A., Stevens, L. A., Matin, A., Hirayama, T., Levine, R. L. and Moss, J. (2002) ADP ribosylation of human neutrophil peptide-1 regulates its biological properties. Proc. Natl. Acad. Sci. U.S.A. 99, 8231-8235
- Takamura-Enya, T., Watanabe, M., Totsuka, Y., Kanazawa, T., Matsushima-Hibiya, Y., Koyama, K., Sugimura, T. and Wakabayashi, K. (2001) Mono(ADP-ribosyl)ation of 2 -deoxyguanosine residue in DNA by an apoptosis-inducing protein, pierisin-1, from cabbage butterfly. Proc. Natl. Acad. Sci. U.S.A. 98, 12414-12419
- Basile, G., Taglialatela-Scafati, O., Damonte, G., Armirotti, A., Bruzzone, S., Guida, L., Franco, L., Usai, C., Fattorusso, E., De Flora, A. and Zocchi, E. (2005) ADP-ribosyl cyclases generate two unusual adenine homodinucleotides with cytotoxic activity on mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 102, 14509-14514
- Tanner, K. G., Landry, J., Sternglanz, R. and Denu, J. M. (2000) Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc. Natl. Acad. Sci. U.S.A. 97, 14178-14182
- Lakowicz, J. R., Szmacinski, H., Nowaczyk, K. and Johnson, M. L. (1992) Fluorescence lifetime imaging of free and protein-bound NADH. Proc. Natl. Acad. Sci. U.S.A. 89, 1271-1275
- Rydstrom, J., Hoek, J. B. and Ernster, L. (1976) Nicotinamide nucleotide transhydrogenases. In The Enzymes (Boyer, P.D., ed.), pp. 51-88, Academic Press, New York
- Luzzatto, L. (1993) Glucose 6-phosphate dehydrogenase deficiency and hemolytic anemia. In Hematology of Infancy and Childhood. (Nathan, D. G. and Oski, D. F., eds), pp. 674-691, W. B. Saunders, Philadelphia 63
- Weber, G. (1987), Strongly conserved segment of gene expression in cancer cells. In Modulation of Liver Cell Expression (W. Reutter, H. Popper, I. M. Arias, P. C. Heinrich, D. Keppler, and L. Landmann, eds), pp. 303-314, MTP, Lancaster 64
- Grose, J. H., Joss, L., Velick, S. F. and Roth, J. R. (2006) Evidence that feedback inhibition of NAD kinase controls responses to oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 103, 7601-7606 100
- Kobayashi, K., Ehrlich, S. D., Albertini, A., Amati, G., Andersen, K. K., Arnaud, M., Asai, K., Ashikaga, S., Aymerich, S., Bessieres, P. et al. (2003) Essential Bacillus subtilis genes. Proc. Natl. Acad. Sci. U.S.A. 100, 4678-4683 101
- Foerder, C. A., Klebanoff, S. J. and Shapiro, B. M. (1978) Hydrogen peroxide production, chemiluminescence, and the respiratory burst of fertilization: interrelated events in early sea urchin development. Proc. Natl. Acad. Sci. U.S.A. 75, 3183-3187 145
- Heinecke, J. W. and Shapiro, B. M. (1989) Respiratory burst oxidase of fertilization. Proc. Natl. Acad. Sci. U.S.A. 86, 1259-1263 146
- Foerder, C. A. and Shapiro, B. M. (1977) Release of ovoperoxidase from sea urchin eggs hardens the fertilization membrane with tyrosine crosslinks. Proc. Natl. Acad. Sci. U.S.A. 74, 4214-4218 147
- Butcher, R. A. and Schreiber, S. L. (2004) Identification of Ald6p as the target of a class of small-molecule suppressors of FK506 and their use in network dissection. Proc. Natl. Acad. Sci. U.S.A. 101, 7868-7873 151
Cited by
Sorted by citations
The return of metabolism: biochemistry and physiology of the pentose phosphate pathway
Stincone, A., Prigione, A., Cramer, T., Wamelink, M. M. C., Campbell, K., Cheung, E., Olin‐Sandoval, V., Grüning, N., Krüger, A., Tauqeer Alam, M., et al. (2015) · Biological Reviews · doi:10.1111/brv.12140 · Cited by 1,576 · see citing works
Ying, W. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1672 · Cited by 1,494 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
The Sedoheptulose Kinase CARKL Directs Macrophage Polarization through Control of Glucose Metabolism
Haschemi, A., Kosma, P., Gille, L., Evans, C. R., Burant, C. F., Starkl, P., Knapp, B., Haas, R., Schmid, J. A., Jandl, C., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.023 · Cited by 635 · see citing works
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes
Liu, L., Su, X., Quinn, W. J., Hui, S., Krukenberg, K., Frederick, D. W., Redpath, P., Zhan, L., Chellappa, K., White, E., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.018 · Cited by 564 · see citing works
Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells
Lewis, C. A., Parker, S. J., Fiske, B. P., McCloskey, D., Gui, D. Y., Green, C. R., Vokes, N. I., Feist, A. M., Vander Heiden, M. G., & Metallo, C. M. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.008 · Cited by 562 · see citing works
Watson, M., Roulston, A., Bélec, L., Billot, X., Marcellus, R., Bédard, D., Bernier, C., Branchaud, S., Chan, H., Dairi, K., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00112-09 · Cited by 229 · see citing works
Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging
Bradshaw, P. C. (2019) · Nutrients · doi:10.3390/nu11030504 · Cited by 178 · see citing works
NAD+ flux is maintained in aged mice despite lower tissue concentrations
McReynolds, M. R., Chellappa, K., Chiles, E., Jankowski, C., Shen, Y., Chen, L., Descamps, H. C., Mukherjee, S., Bhat, Y. R., Lingala, S. R., et al. (2021) · Cell Systems · doi:10.1016/j.cels.2021.09.001 · Cited by 112 · see citing works
NAD <sup>+</sup> Biosynthesis and Signaling in Plants
Gakière, B., Hao, J., de Bont, L., Pétriacq, P., Nunes-Nesi, A., & Fernie, A. R. (2018) · Critical Reviews in Plant Sciences · doi:10.1080/07352689.2018.1505591 · Cited by 108 · see citing works
Ljungberg, M. C., Ali, Y. O., Zhu, J., Wu, C.-S., Oka, K., Zhai, R. G., & Lu, H.-C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr492 · Cited by 107 · see citing works
Calcium mobilizing second messengers derived from NAD
Guse, A. H. (2015) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2014.12.015 · Cited by 82 · see citing works
Yoo, C.-H., Kim, J., Baek, H.-M., Chang, K.-A., & Choe, B.-Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065073 · Cited by 13 · see citing works
- Authors
- Pollak, N., Dölle, C., & Ziegler, M.
- Affiliations
- University of Bergen (NO)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2007-02-12
- Volume
- 402
- Issue
- 2
- Pages
- 205-218
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1798440
- OpenAlex
- W2014880757
- Cited by
- 730
- References
- 4
- Citations by year
- 2026: 28 · 2025: 39 · 2024: 29 · 2023: 48 · 2022: 32 · 2021: 37 · 2020: 38 · 2019: 57 · 2018: 40 · 2017: 42 · 2016: 38 · 2015: 40 · 2014: 57 · 2013: 30 · 2012: 38
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kreftforeningen
- Deutsche Forschungsgemeinschaft
- Norges Forskningsråd
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- pyridine nucleotides, NAD+, NADPH, NAD biosynthesis, ADP-ribosylation, cyclic ADP-ribose, NAADP, intracellular calcium signaling, NAD kinase, reducing equivalents, oxidative damage, NADPH/NADP+ ratio, energy transduction
- MeSH terms
- Animals, Humans, NAD, NADP, Substrate Specificity, Signal Transduction, Reactive Oxygen Species, Phosphotransferases (Alcohol Group Acceptor)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
