Chemo-enzymatic synthesis of isotopically labeled nicotinamide riboside.
Chemo-enzymatic synthesis of isotopically labeled nicotinamide riboside.
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同位素标记的烟酰胺核苷的化学酶合成。
DOI：
10.1039/c8ob00552d
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发表时间：
2018
影响因子：
3.2
通讯作者：
Cen,Yana
中科院分区：
文献类型：
--
作者：
Tran,Ai;Yokose,Ryota;Cen,Yana
作为许多反应的辅助因子，NAD+被发现广泛分布在许多细胞代谢图中。仅这一核心氧化还原作用就使NAD+的生物合成引起了极大的兴趣。最近的研究揭示了NAD+作为多种酶的底物的新生物学作用，这些酶调节了广泛的关键细胞任务。这些消耗NAD+的酶进一步强调了理解NAD+生物合成途径的重要性。在这项研究中，我们开发了一种化学酶法合成同位素标记的NAD+前体烟酰胺核苷（NR）。NR同位素体的合成使我们能够明确地确定NR在细胞环境中有效地转化为NAD+，而不依赖于烟酰胺的降解，并且它以完整的形式被纳入NAD+中。多用途的合成方法以及同位素标记的NRs将为进一步破译重要而复杂的NAD+代谢提供有力的工具。
As a cofactor for numerous reactions, NAD+ is found widely dispersed across many maps of cellular metabolism. This core redox role alone makes the biosynthesis of NAD+ of great interest. Recent studies have revealed new biological roles for NAD+ as a substrate for diverse enzymes that regulate a broad spectrum of key cellular tasks. These NAD+-consuming enzymes further highlight the importance of understanding NAD+ biosynthetic pathways. In this study, we developed a chemo-enzymatic synthesis of isotopically labeled NAD+ precursor, nicotinamide riboside (NR). The synthesis of NR isotopomers allowed us to unambiguously determine that NR is efficiently converted to NAD+ in the cellular environment independent of degradation to nicotinamide, and it is incorporated into NAD+ in its intact form. The versatile synthetic method along with the isotopically labeled NRs will provide powerful tools to further decipher the important yet complicated NAD+ metabolism.