Abstract
Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that regulates various metabolic pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Additionally, NAD serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD glycohydrolase, and it regulates DNA repair, gene expression, energy metabolism, and stress responses. Many studies have demonstrated that NAD metabolism is deeply involved in aging and aging-related diseases. Previously, we demonstrated that nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD), which are analogs of NAD, are significantly increased in Nmnat3-overexpressing mice. However, there is insufficient knowledge about NGD and NHD in vivo. In the present study, we aimed to investigate the metabolism and biochemical properties of these NAD analogs. We demonstrated that endogenous NGD and NHD were found in various murine tissues, and their synthesis and degradation partially rely on Nmnat3 and CD38. We have also shown that NGD and NHD serve as coenzymes for alcohol dehydrogenase (ADH) in vitro, although their affinity is much lower than that of NAD. On the other hand, NGD and NHD cannot be used as substrates for SIRT1, SIRT3, and PARP1. These results reveal the basic metabolism of NGD and NHD and also highlight their biological function as coenzymes.
Highlights
Nicotinamide adenine dinucleotide (NAD) is an essential cofactor that mediates various redox reactions through the transfer of electrons between NAD+ and NADH
The levels of nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD) in the liver of nicotinamide mononucleotide adenylyltransferase (Nmnat)[3] KO mice were almost the same as those in wild-type (WT) controls (Table 3). These results indicate that the production of NGD and NHD in red blood cells (RBCs) primarily depends on Nmnat[3], but other Nmnat isozymes, such as Nmnat[1], may be involved in the production of NGD and NHD in other tissues, including the liver
NHD had a higher affinity for alcohol dehydrogenase (ADH) than did NGD (Fig. 4G). These results indicate that NGD and NHD can serve as coenzymes but that they have an affinity for ADH that is much lower than that of NAD
Summary
Nicotinamide adenine dinucleotide (NAD) is an essential cofactor that mediates various redox reactions through the transfer of electrons between NAD+ (oxidized form of NAD, hereafter referred to as NAD) and NADH (reduced form of NAD, hereafter referred to as NADH). Many studies have demonstrated that NAD levels decrease with aging in various tissues of rodents and humans, and the decline of NAD levels is involved in the pathogenesis of aging-related diseases, www.nature.com/scientificreports/. Nicotinamide mononucleotide adenylyltransferase (Nmnat) transfers an adenylyl moiety from ATP to NMN to generate NAD13. Overexpression of Nmnat[3] in mice efficiently increases mitochondrial NAD levels with favorable effects on metabolic decline with aging[17]. These results indicate that Nmnat[3] is dispensable for mitochondrial NAD maintenance, but overexpression of Nmnat[3] in mice is sufficient to increase mitochondrial NAD levels. We aimed to investigate the metabolism and biochemical properties of NGD and NHD
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
