2. Academic Validation
  3. Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)

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

  • Sci Rep. 2019 Sep 11;9(1):13102. doi: 10.1038/s41598-019-49547-6.
Keisuke Yaku 1,  Keisuke Okabe 1 2,  Maryam Gulshan 1,  Kiyoshi Takatsu 3 4,  Hiroshi Okamoto 5 6,  Takashi Nakagawa 7 8
Affiliations

Affiliations

  • 1 Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, 930-0194, Japan.
  • 2 First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, 930-0194, Japan.
  • 3 Toyama Prefectural Institute for Pharmaceutical Research, Toyama, 939-0363, Japan.
  • 4 Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, 930-0194, Japan.
  • 5 Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
  • 6 Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
  • 7 Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, 930-0194, Japan. nakagawa@med.u-toyama.ac.jp.
  • 8 Institute of Natural Medicine, University of Toyama, Toyama, 930-0194, Japan. nakagawa@med.u-toyama.ac.jp.
PMID: 31511627 DOI: 10.1038/s41598-019-49547-6
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.

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