The Biochemical Pathways of Nicotinamide-Derived Pyridones
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The Biochemical Pathways of Nicotinamide-Derived Pyridones. / Hayat, Faisal; Sonavane, Manoj; Makarov, Mikhail V.; Trammell, Samuel A.J.; McPherson, Pamela; Gassman, Natalie R.; Migaud, Marie E.
I: International Journal of Molecular Sciences, Bind 22, Nr. 3, 1145, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The Biochemical Pathways of Nicotinamide-Derived Pyridones
AU - Hayat, Faisal
AU - Sonavane, Manoj
AU - Makarov, Mikhail V.
AU - Trammell, Samuel A.J.
AU - McPherson, Pamela
AU - Gassman, Natalie R.
AU - Migaud, Marie E.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - NAD
KW - Nicotinamide
KW - Pyridones
KW - Redox cofactor
U2 - 10.3390/ijms22031145
DO - 10.3390/ijms22031145
M3 - Journal article
C2 - 33498933
AN - SCOPUS:85099770166
VL - 22
JO - International Journal of Molecular Sciences (CD-ROM)
JF - International Journal of Molecular Sciences (CD-ROM)
SN - 1424-6783
IS - 3
M1 - 1145
ER -
ID: 257925242