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BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities

Author

Listed:
  • Keisuke Yaku

    (University of Toyama)

  • Sailesh Palikhe

    (University of Toyama)

  • Hironori Izumi

    (University of Toyama
    University of Toyama)

  • Tomoyuki Yoshida

    (University of Toyama
    University of Toyama)

  • Keisuke Hikosaka

    (University of Toyama)

  • Faisal Hayat

    (University of South Alabama)

  • Mariam Karim

    (University of Toyama)

  • Tooba Iqbal

    (University of Toyama)

  • Yasuhito Nitta

    (University of Toyama)

  • Atsushi Sato

    (Tokyo University of Technology)

  • Marie E. Migaud

    (University of South Alabama)

  • Katsuhiko Ishihara

    (Kawasaki Medical University)

  • Hisashi Mori

    (University of Toyama
    University of Toyama
    University of Toyama)

  • Takashi Nakagawa

    (University of Toyama
    University of Toyama)

Abstract

Nicotinamide riboside (NR) is one of the orally bioavailable NAD+ precursors and has been demonstrated to exhibit beneficial effects against aging and aging-associated diseases. However, the metabolic pathway of NR in vivo is not yet fully understood. Here, we demonstrate that orally administered NR increases NAD+ level via two different pathways. In the early phase, NR was directly absorbed and contributed to NAD+ generation through the NR salvage pathway, while in the late phase, NR was hydrolyzed to nicotinamide (NAM) by bone marrow stromal cell antigen 1 (BST1), and was further metabolized by the gut microbiota to nicotinic acid, contributing to generate NAD+ through the Preiss–Handler pathway. Furthermore, we report BST1 has a base-exchange activity against both NR and nicotinic acid riboside (NAR) to generate NAR and NR, respectively, connecting amidated and deamidated pathways. Thus, we conclude that BST1 plays a dual role as glycohydrolase and base-exchange enzyme during oral NR supplementation.

Suggested Citation

  • Keisuke Yaku & Sailesh Palikhe & Hironori Izumi & Tomoyuki Yoshida & Keisuke Hikosaka & Faisal Hayat & Mariam Karim & Tooba Iqbal & Yasuhito Nitta & Atsushi Sato & Marie E. Migaud & Katsuhiko Ishihara, 2021. "BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27080-3
    DOI: 10.1038/s41467-021-27080-3
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    Cited by:

    1. Miyuki Nomura & Mai Ohuchi & Yoshimi Sakamoto & Kei Kudo & Keisuke Yaku & Tomoyoshi Soga & Yuki Sugiura & Mami Morita & Kayoko Hayashi & Shuko Miyahara & Taku Sato & Yoji Yamashita & Shigemi Ito & Nao, 2023. "Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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