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Open AccessArticle

The Biochemical Pathways of Nicotinamide-Derived Pyridones

1
Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA
2
Mitchell Cancer Institute, College of Medicine, University of South Alabama, Mobile, AL 36604, USA
3
Department of Physiology & Cell Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA
4
Novo Nordisk Foundation, Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Shared first authorship.
Academic Editor: Maurizio Battino
Int. J. Mol. Sci. 2021, 22(3), 1145; https://doi.org/10.3390/ijms22031145
Received: 28 December 2020 / Revised: 18 January 2021 / Accepted: 19 January 2021 / Published: 24 January 2021
(This article belongs to the Collection Feature Papers in Bioactives and Nutraceuticals)
As catabolites of nicotinamide possess physiological relevance, pyridones are often included in metabolomics measurements and associated with pathological outcomes in acute kidney injury (AKI). Pyridones are oxidation products of nicotinamide, its methylated form, and its ribosylated form. While they are viewed as markers of over-oxidation, they are often wrongly reported or mislabeled. To address this, we provide a comprehensive characterization of these catabolites of vitamin B3, justify their nomenclature, and differentiate between the biochemical pathways that lead to their generation. Furthermore, we identify an enzymatic and a chemical process that accounts for the formation of the ribosylated form of these pyridones, known to be cytotoxic. Finally, we demonstrate that the ribosylated form of one of the pyridones, the 4-pyridone-3-carboxamide riboside (4PYR), causes HepG3 cells to die by autophagy; a process that occurs at concentrations that are comparable to physiological concentrations of this species in the plasma in AKI patients. View Full-Text
Keywords: NAD; redox cofactor; nicotinamide; pyridones NAD; redox cofactor; nicotinamide; pyridones
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MDPI and ACS Style

Hayat, F.; Sonavane, M.; Makarov, M.V.; Trammell, S.A.J.; McPherson, P.; Gassman, N.R.; Migaud, M.E. The Biochemical Pathways of Nicotinamide-Derived Pyridones. Int. J. Mol. Sci. 2021, 22, 1145. https://doi.org/10.3390/ijms22031145

AMA Style

Hayat F, Sonavane M, Makarov MV, Trammell SAJ, McPherson P, Gassman NR, Migaud ME. The Biochemical Pathways of Nicotinamide-Derived Pyridones. International Journal of Molecular Sciences. 2021; 22(3):1145. https://doi.org/10.3390/ijms22031145

Chicago/Turabian Style

Hayat, Faisal; Sonavane, Manoj; Makarov, Mikhail V.; Trammell, Samuel A.J.; McPherson, Pamela; Gassman, Natalie R.; Migaud, Marie E. 2021. "The Biochemical Pathways of Nicotinamide-Derived Pyridones" Int. J. Mol. Sci. 22, no. 3: 1145. https://doi.org/10.3390/ijms22031145

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