BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities.
BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities.
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DOI：
10.1038/s41467-021-27080-3
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发表时间：
2021-11-19
影响因子：
16.6
通讯作者：
Nakagawa T
中科院分区：
文献类型：
--
作者：
Yaku K;Palikhe S;Izumi H;Yoshida T;Hikosaka K;Hayat F;Karim M;Iqbal T;Nitta Y;Sato A;Migaud ME;Ishihara K;Mori H;Nakagawa T
烟酰胺核苷（NR）是一种口服生物可利用的NAD+前体，已被证明对衰老和衰老相关疾病具有有益作用。然而，NR在体内的代谢途径尚未完全清楚。在这里，我们证明了口服NR通过两种不同的途径增加NAD+水平。在早期阶段，NR被直接吸收，并通过NR补救途径促进NAD+的产生，而在晚期阶段，NR被骨髓基质细胞抗原1（BST 1）水解为烟酰胺（NAM），并进一步被肠道微生物群代谢为烟酸，通过Preiss-nucleotide途径促进NAD+的产生。此外，我们报告BST 1具有对NR和烟酸核苷（NAR）的碱基交换活性，分别产生NAR和NR，连接酰胺化和脱酰胺化途径。因此，我们得出结论，BST 1在口服NR补充过程中起着糖水解酶和碱交换酶的双重作用。烟酰胺核苷（NR）是一种NAD +前体，表现出抗衰老的有益作用。在这里，作者证明了口服NR以双相方式增加NAD +水平，骨髓基质细胞抗原1在NR合成NAD +中起着至关重要的作用。
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. Nicotinamide riboside (NR) is a NAD + precursor exhibiting beneficial effects against aging. Here the authors demonstrate that orally administered NR increases NAD + levels in a diphasic manner and that bone marrow stromal cell antigen 1 plays a crucial role for NAD + synthesis from NR.
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影响因子：
20.8
作者：
Chini CCS;Peclat TR;Warner GM;Kashyap S;Espindola-Netto JM;de Oliveira GC;Gomez LS;Hogan KA;Tarragó MG;Puranik AS;Agorrody G;Thompson KL;Dang K;Clarke S;Childs BG;Kanamori KS;Witte MA;Vidal P;Kirkland AL;De Cecco M;Chellappa K;McReynolds MR;Jankowski C;Tchkonia T;Kirkland JL;Sedivy JM;van Deursen JM;Baker DJ;van Schooten W;Rabinowitz JD;Baur JA;Chini EN
通讯作者：
Chini EN
影响因子：
14.9
作者：
Chen, Shih-Hsun;Yu, Xiaochun
通讯作者：
Yu, Xiaochun
DOI：
10.1073/pnas.1718819115
发表时间：
2018-02-20
影响因子：
11.1
作者：
Hou, Yujun;Lautrup, Sofie;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.
影响因子：
7.1
作者：
Dollerup, Ole L.;Christensen, Britt;Jessen, Niels
通讯作者：
Jessen, Niels
影响因子：
1.6
作者：
Hussain, AMM;Lee, HC;Chang, CF
通讯作者：
Chang, CF