Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)

• Published in: Scientific reports Vol. 9; no. 1; pp. 13102 - 12
• Main Authors: Yaku, Keisuke, Okabe, Keisuke, Gulshan, Maryam, Takatsu, Kiyoshi, Okamoto, Hiroshi, Nakagawa, Takashi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.09.2019; Nature Publishing Group
• Subjects: 631/45/607; 64/60; 692/163/2743; Adenine; Adenosine diphosphate; Aging; Aging - metabolism; Alcohol dehydrogenase; Animals; CD38 antigen; Coenzymes; DNA repair; Energy metabolism; Gene expression; Glycolysis; Guanine; Guanine Nucleotides - biosynthesis; Guanine Nucleotides - metabolism; Guanosine Triphosphate - metabolism; Humanities and Social Sciences; Hypoxanthine; Inosine Triphosphate - metabolism; Metabolic pathways; Metabolism; Mice; multidisciplinary; NAD; NAD - analogs & derivatives; NAD - biosynthesis; NAD - metabolism; Nicotinamide; Oxidation; Oxidative phosphorylation; Phosphorylation; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - metabolism; Ribose; Science; Science (multidisciplinary); SIRT1 protein; Sirtuins - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49547-6

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.