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However, the metabolic pathway of NR in vivo is not yet fully understood. Here, we demonstrate that orally administered NR increases NAD\n                    <jats:sup>+<\/jats:sup>\n                    level via two different pathways. In the early phase, NR was directly absorbed and contributed to NAD\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    through the Preiss\u2013Handler 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.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-27080-3","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T06:02:53Z","timestamp":1637301773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities"],"prefix":"10.1038","volume":"12","author":[{"given":"Keisuke","family":"Yaku","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailesh","family":"Palikhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Izumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-3798","authenticated-orcid":false,"given":"Tomoyuki","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Hikosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Hayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Karim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tooba","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Nitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie E.","family":"Migaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-5188","authenticated-orcid":false,"given":"Katsuhiko","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-2456","authenticated-orcid":false,"given":"Hisashi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-7605","authenticated-orcid":false,"given":"Takashi","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"27080_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.arr.2018.05.006","volume":"47","author":"K Yaku","year":"2018","unstructured":"Yaku, K., Okabe, K. & Nakagawa, T. 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