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

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, Hisashi Mori and Takashi Nakagawa ()
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Keisuke Yaku: University of Toyama
Sailesh Palikhe: University of Toyama
Hironori Izumi: University of Toyama
Tomoyuki Yoshida: University of Toyama
Keisuke Hikosaka: University of Toyama
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
Takashi Nakagawa: University of Toyama

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27080-3

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DOI: 10.1038/s41467-021-27080-3

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