参考文献

Nicotinamide adenine dinucleotide is transported into mammalian mitochondria

Antonio Davila, Ling Liu, Karthikeyani Chellappa, Philip Redpath, Eiko Nakamaru-Ogiso, Lauren M Paolella, Zhigang Zhang, Marie E Migaud, Joshua D Rabinowitz

Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, United States; University of Pennsylvania, United States;Princeton University, United States; Queen’s University Belfast, United Kingdom; Perelman School of Medicine, University of Pennsylvania, United States; Northeast Agricultural University, China; University of South Alabama, United States

Abstract

Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate that NAD(H) is the imported species. Our results challenge the long-held view that the mitochondrial inner membrane is impermeable to pyridine nucleotides and suggest the existence of an unrecognized mammalian NAD (or NADH) transporter.

https://elifesciences.org/articles/33246

β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats.

 Kawamura T1, Mori N, Shibata K.

Abstract

The turnover of the oxidized form of nicotinamide adenine dinucleotide (NAD+) has attracted interest in regard to longevity. Thus, compounds that can rapidly increase the cellular NAD+ concentration have been surveyed by many researchers. Of those, β-nicotinamide mononucleotide (β-NMN) has been focused on. Studies on the biosynthesis of NAD+ from β-NMN have been reported at the cellular level, but not at the whole animal level. In the present study, we investigated whether β-NMN is superior to nicotinamide (Nam) as a precursor of NAD+ in whole animal experiments. To this end we compared the NAD+ concentration in the blood and the urinary excretion amounts of NAD+ catabolites. Rats were intraperitoneally injected with β-NMN or Nam. After the injection, blood samples and urine samples were collected at 3-h intervals. The concentration of blood total NAD (NAD11NADH) in each sample showed no significant differences between the two groups. The urinary excretion amounts of NAD+ catabolites in the urine samples collected at 3-6 h after the injection were lower in the β-NMN group than in the Nam group. These results suggest that β-NMN is retained in the body for longer than Nam.

https://www.ncbi.nlm.nih.gov/pubmed/27725413

Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice

Kathryn F. Mills,1 Shohei Yoshida,2 Liana R. Stein,1,§ Alessia Grozio,1 Shunsuke Kubota,3 Yo Sasaki,4Philip Redpath,5 Marie E. Migaud,5 Rajendra S. Apte,1,3 Koji Uchida,2 Jun Yoshino,6,* and Shin-ichiro Imai1,*

Summary

NAD+ availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models. In this study, we conducted a 12 month-long NMN administration to regular chow-fed wild-type C57BL/6N mice during their normal aging. Orally administered NMN was quickly utilized to synthesize NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice. Without any obvious toxicity or deleterious effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies. Consistent with these phenotypes, NMN prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential of NAD+

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668137/

Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule

Saikat Kumar Poddar 1,*,Ali Ehsan Sifat 1,Sanjana Haque 1,Noor Ahmed Nahid 1,Sabiha Chowdhury 1 andImtias Mehedi 2

1.Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh

2.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh

Abstract

Nicotinamide mononucleotide (NMN) is a nucleotide that is most recognized for its role as an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis. Although the biosynthetic pathway of NMN varies between eukaryote and prokaryote, two pathways are mainly followed in case of eukaryotic human—one is through the salvage pathway using nicotinamide while the other follows phosphorylation of nicotinamide riboside. Due to the unavailability of a suitable transporter, NMN enters inside the mammalian cell in the form of nicotinamide riboside followed by its subsequent conversion to NMN and NAD+. This particular molecule has demonstrated several beneficial pharmacological activities in preclinical studies, which suggest its potential therapeutic use. Mostly mediated by its involvement in NAD+ biosynthesis, the pharmacological activities of NMN include its role in cellular biochemical functions, cardioprotection, diabetes, Alzheimer’s disease, and complications associated with obesity. The recent groundbreaking discovery of anti-ageing activities of this chemical moiety has added a valuable essence in the research involving this molecule. This review focuses on the biosynthesis of NMN in mammalian and prokaryotic cells and mechanism of absorption along with the reported pharmacological activities in murine model. View Full-Text

Keywords: ageing; Alzheimer’s disease; diabetes; ischemic preconditioning; nicotinamide mononucleotide; obesity

https://www.mdpi.com/2218-273X/9/1/34