Notes

Cellular metabolism | microorganisms promote mammalian nad synthesis through metabolic bypass
PQQ (Pyrroloquinoline quinone),

Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme in all cells. As an electron transfer coenzyme, it participates in hundreds of metabolic reactions and plays an irreplaceable role in controlling cell energy metabolism, genome stability, immune response, biological cycle and aging [1-3]. However, the mechanism by which intracellular nad metabolism is controlled by environmental factors remains unclear.
Fig. 1 nad metabolic pathway in mammalian cells
The study of intracellular nad homeostasis has important application significance. For example, in order to maintain rapid proliferation, cancer cells need to produce a large amount of ATP, and NAD is necessary for ATP synthesis. Therefore, many cancer cells highly express the amide pathway limiting enzyme Nampt. Therefore, Nampt is one of the important targets of antitumor drugs [6,7]. On the other hand, the concentration of NAD decreases with age [8]. In recent years, a series of studies have shown that several nad synthesis precursors in amide pathway, such as nicotinamide mononucleotide (NMN) and nicotinamide nucleoside (NR), can effectively increase the concentration of NAD in animal models and prevent or delay a series of senile diseases. Therefore, NMN and natural rubber have recently been recommended by nutritionists as "magic drugs" for anti-aging. In these experiments, it is considered that NMN and NR bypass the rate limiting stage of Nampt through amide pathway, thereby increasing nad concentration [9].
On March 3, 2020, Li Xiaoling and Xiaoling research group of Institute of Environmental Health Sciences of National Institutes of health, Jason Williams, director of mass spectrometry platform, Professor Jason locasale of Duke University, etc. jointly published in the journal Cell metallurgy. This study shows for the first time that using metabolomics, stable isotope tracking technology and sterile mouse model, bacteria, especially intestinal microorganisms, can promote nad synthesis in mammalian cells and tissues through unconventional alternative deamidation pathways, It further shows that the intestinal microbial mediated deamidation nad synthesis pathway is the main mechanism for the up regulation of NAD concentration in mammalian cells by oral amide pathway nad synthesis precursors such as Nr.
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