Defining NAD(P)(H) Catabolism
- PMID: 37447389
- PMCID: PMC10346783
- DOI: 10.3390/nu15133064
Defining NAD(P)(H) Catabolism
Abstract
Dietary vitamin B3 components, such as nicotinamide and nicotinic acid, are precursors to the ubiquitous redox cofactor nicotinamide adenine dinucleotide (NAD+). NAD+ levels are thought to decline with age and disease. While the drivers of this decline remain under intense investigation, strategies have emerged seeking to functionally maintain NAD+ levels through supplementation with NAD+ biosynthetic intermediates. These include marketed products, such as nicotinamide riboside (NR) and its phosphorylated form (NMN). More recent developments have shown that NRH (the reduced form of NR) and its phosphorylated form NMNH also increases NAD+ levels upon administration, although they initially generate NADH (the reduced form of NAD+). Other means to increase the combined levels of NAD+ and NADH, NAD(H), include the inhibition of NAD+-consuming enzymes or activation of biosynthetic pathways. Multiple studies have shown that supplementation with an NAD(H) precursor changes the profile of NAD(H) catabolism. Yet, the pharmacological significance of NAD(H) catabolites is rarely considered although the distribution and abundance of these catabolites differ depending on the NAD(H) precursor used, the species in which the study is conducted, and the tissues used for the quantification. Significantly, some of these metabolites have emerged as biomarkers in physiological disorders and might not be innocuous. Herein, we review the known and emerging catabolites of the NAD(H) metabolome and highlight their biochemical and physiological function as well as key chemical and biochemical reactions leading to their formation. Furthermore, we emphasize the need for analytical methods that inform on the full NAD(H) metabolome since the relative abundance of NAD(H) catabolites informs how NAD(H) precursors are used, recycled, and eliminated.
Keywords: NAD(P)(H) catabolism; NAD+ metabolism; methyl-nicotinamide; niacin; nicotinamide; pyridone.
Conflict of interest statement
M.E.M. and J.D. are funded by Elysium Health; R.W.D. is employed by Elysium Health.
Figures
Similar articles
-
Chemical and Biochemical Reactivity of the Reduced Forms of Nicotinamide Riboside.ACS Chem Biol. 2021 Apr 16;16(4):604-614. doi: 10.1021/acschembio.0c00757. Epub 2021 Mar 30. ACS Chem Biol. 2021. PMID: 33784074 Free PMC article.
-
Dihydronicotinamide riboside is a potent NAD+ concentration enhancer in vitro and in vivo.J Biol Chem. 2019 Jun 7;294(23):9295-9307. doi: 10.1074/jbc.RA118.005772. Epub 2019 Apr 4. J Biol Chem. 2019. PMID: 30948509 Free PMC article.
-
NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health.Curr Nutr Rep. 2023 Sep;12(3):445-464. doi: 10.1007/s13668-023-00475-y. Epub 2023 Jun 5. Curr Nutr Rep. 2023. PMID: 37273100 Free PMC article. Review.
-
NAD Metabolome Analysis in Human Cells Using ¹H NMR Spectroscopy.Int J Mol Sci. 2018 Dec 6;19(12):3906. doi: 10.3390/ijms19123906. Int J Mol Sci. 2018. PMID: 30563212 Free PMC article.
-
Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts.Nutrients. 2022 Aug 7;14(15):3231. doi: 10.3390/nu14153231. Nutrients. 2022. PMID: 35956406 Free PMC article. Review.
Cited by
-
Time-restricted feeding ameliorates non-alcoholic fatty liver disease through modulating hepatic nicotinamide metabolism via gut microbiota remodeling.Gut Microbes. 2024 Jan-Dec;16(1):2390164. doi: 10.1080/19490976.2024.2390164. Epub 2024 Aug 18. Gut Microbes. 2024. PMID: 39154362 Free PMC article.
-
Transcriptome in Liver of Periparturient Dairy Cows Differs between Supplementation of Rumen-Protected Niacin and Rumen-Protected Nicotinamide.Metabolites. 2024 Mar 1;14(3):150. doi: 10.3390/metabo14030150. Metabolites. 2024. PMID: 38535310 Free PMC article.
-
Regulation of and challenges in targeting NAD+ metabolism.Nat Rev Mol Cell Biol. 2024 Oct;25(10):822-840. doi: 10.1038/s41580-024-00752-w. Epub 2024 Jul 18. Nat Rev Mol Cell Biol. 2024. PMID: 39026037 Review.
-
Synthesis, Detection, and Metabolism of Pyridone Ribosides, Products of NAD Overoxidation.Chem Res Toxicol. 2024 Feb 19;37(2):248-258. doi: 10.1021/acs.chemrestox.3c00264. Epub 2024 Jan 10. Chem Res Toxicol. 2024. PMID: 38198686 Free PMC article.
-
Multi-Omics Reveals the Effects of Spirulina platensis Powder Replacement of Fish Meal on Intestinal Metabolism and Stress in Zig-Zag Eel (Mastacembelus armatus).Antioxidants (Basel). 2024 Jul 15;13(7):851. doi: 10.3390/antiox13070851. Antioxidants (Basel). 2024. PMID: 39061919 Free PMC article.
References
-
- Arthur H. The alcoholic ferment of yeast-juice. Proc. R. Soc. Lond. B. 1906;77:405–420. doi: 10.1098/rspb.1906.0029. - DOI
-
- Harden A. The alcoholic ferment of yeast-juice. Part II.-The coferment of yeast-juice. Proc. R. Soc. B Biol. Sci. 1906;78:369–375.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
