Nicotinamide Deamidation by Microorganisms in Rat Stomach

Abstract

We have extended our investigation of nicotinamide deamidation in the stomach of conventional rats. The bacterial species in the pars preventricularis were identified as Flavobacterium peregrinum, Escherichia coli, Streptococcus faecalis, and Lactobacillus acidophilus, listed in order of decreasing deamidase activity. Nicotinamide-7-14C ingested into rat stomach was rapidly deamidated to nicotinic acid. These results contribute to the accumulated evidence that microorganisms present in the pars preventricularis of rat stomach are responsible for the deamidation of nicotinamide to nicotinic acid, a known precursor of mammalian pyridine nucleotides.It has been well recognized that the biosynthesis of nicotinamide adenine dinucleotide (NAD) in mammals can occur through the operation of three different pathways ( Fig.

Nicotinamide mononucleotide (NMN) deamidation by host-microbiome interactions

“…4-7), indicating either cleavage of the labile glycosidic bond of NMN, or rapid recycling of NAD + , as described previously (Liu et al, 2018). Following cleavage of the glycosidic bond to release free Nam, its deamidation in the GIT (Shimoyama et al, 1971;Tanigawa et al, 1970) by the bacterial enzyme PncA (Shats et al, 2020) also likely contributes to these changes.…”

“…5, 8), indicating either cleavage of the labile glycosidic bond of NMN prior to its incorporation, or rapid recycling of NAD + 50 . Following cleavage of the glycosidic bond to release free Nam, its deamidation in the GIT 51, 52 by the bacterial enzyme PncA 44 also likely contributes to these changes.…”

Nicotinamide adenine dinucleotide biosynthesis and pyridine nucleotide cycle metabolism in microbial systems.

“…Cells that possess an intact PNC, and many cells that do not, use the Preiss-Handler pathway to synthesize NAD from NA (52,85,86). Similarly, NAm deamidase, whose enzymatic function is to convert NAm to NA, is also present in all cells that can completely recycle NAD (52, 55,92,99,106) through NA. The pathway of degradation from NAD to NAm, however, varies among different species.…”

Host–microbiome interactions in nicotinamide mononucleotide (NMN) deamidation

“…A key question here is how direct deamidation of NMN (or NR) contributes to the overall deamidation of orally delivered NMN when compared to the deamidation of nicotinamide into nicotinic acid, where nicotinamide would be released following the breakdown of NMN and/or NAD + [62,63]. If the deamidation of Nam into nicotinic acid was dominant, we would expect to see high levels of M + 1 labelled nicotinic acid, whereas if the deamidation of NMN and its recycling through NAD was the dominant form of deamidation, in the case of NMN1 (M + 6) plus 15 N-Gln (M + 1) we would expect to see greater formation of Nam (M + 2), or in the case of NMN2 (M + 7), we would expect to see more Nam (M + 1).…”

“…10M), indicating either cleavage of the labile glycosidic bond of NMN prior to its incorporation, or intact assimilation and rapid recycling of NAD +55 prior to measurement at the single timepoint used here. If this is due to cleavage of the glycosidic bond to release free Nam in the extracellular space, its deamidation in the GIT [62,63] by the bacterial enzyme PncA [47] likely plays an important role in the incorporation of orally delivered NMN into the de novo pathway for NAD + synthesis.…”