掺杂石墨烯模拟细菌 NADH 氧化酶，在哺乳动物中一步补充 NAD+,Journal of the American Chemical Society

当前位置： X-MOL 学术 › J. Am. Chem. Soc. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

掺杂石墨烯模拟细菌 NADH 氧化酶，在哺乳动物中一步补充 NAD+
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-01-26 , DOI: 10.1021/jacs.2c12336
Xi Liu ₁ , Jingkun Li ₂ , Andrea Zitolo ₃ , Meng Gao ₁ , Jun Jiang ₁ , Xiangtian Geng ₄ , Qianqian Xie ₁ , Di Wu ₁ , Huizhen Zheng ₁ , Xiaoming Cai ₄ , Jianmei Lu ₅ , Frédéric Jaouen ₆ , Ruibin Li ₁

Affiliation

烟酰胺腺嘌呤二核苷酸 (NAD) 是代谢网络的关键调节剂，其氧化形式 NAD ⁺水平下降与多种疾病密切相关。^{虽然用 NAD +}合成所需的前体补充细胞在对抗 NAD ⁺下降方面表现不佳，但另一种策略是开发合成材料，将 NADH 氧化成 NAD ⁺，从而接管 NADH 氧化酶的天然作用（ NOX) 存在于细菌中。在此，我们发现金属氮掺杂石墨烯（MNGR）材料可以催化NADH氧化成NAD ⁺. 在具有不同过渡金属的 MNGR 材料中，Fe-、Co- 和 Cu-NGR 表现出很强的催化活性，同时 NADH 转化为 NAD ⁺的转化率 >80% ，与 NOX 相似的从烟酰胺吡啶环中提取氢的特异性，以及更高的选择性高于其他 51 种纳米材料。FeNGR 的 NOX 样活性在不同的细胞系中发挥良好作用。作为体内应用概念的证明，我们证明了 FeNGR 可以特异性靶向肝脏并修复具有 NAD +^缺陷细胞的肥胖小鼠的代谢通量异常。总的来说，我们的研究通过设计合成材料来模拟细菌中独特酶（例如，NOX）的功能，为探索候选药物提供了独特的见解。

"点击查看英文标题和摘要"

Doped Graphene To Mimic the Bacterial NADH Oxidase for One-Step NAD+ Supplementation in Mammals

Nicotinamide adenine dinucleotide (NAD) is a critical regulator of metabolic networks, and declining levels of its oxidized form, NAD⁺, are closely associated with numerous diseases. While supplementing cells with precursors needed for NAD⁺ synthesis has shown poor efficacy in combatting NAD⁺ decline, an alternative strategy is the development of synthetic materials that catalyze the oxidation of NADH into NAD⁺, thereby taking over the natural role of the NADH oxidase (NOX) present in bacteria. Herein, we discovered that metal-nitrogen-doped graphene (MNGR) materials can catalyze the oxidation of NADH into NAD⁺. Among MNGR materials with different transition metals, Fe-, Co-, and Cu-NGR displayed strong catalytic activity combined with >80% conversion of NADH into NAD⁺, similar specificity to NOX for abstracting hydrogen from the pyridine ring of nicotinamide, and higher selectivity than 51 other nanomaterials. The NOX-like activity of FeNGR functioned well in diverse cell lines. As a proof of concept of the in vivo application, we showed that FeNGR could specifically target the liver and remedy the metabolic flux anomaly in obesity mice with NAD⁺-deficient cells. Overall, our study provides a distinct insight for exploration of drug candidates by design of synthetic materials to mimic the functions of unique enzymes (e.g., NOX) in bacteria.

更新日期：2023-01-26

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南