Dihydronicotinamide riboside (NRH) has been suggested to act as a precursor for the synthesis of NAD⁺, but the biochemical pathway converting it has been unknown. Here, we show that NRH can be converted into NAD⁺ via a salvage pathway in which adenosine kinase (ADK, also known as AK) acts as an NRH kinase. Using isotope-labelling approaches, we demonstrate that NRH is fully incorporated into NAD⁺, with NMNH acting as an intermediate. We further show that AK is enriched in fractions from cell lysates with NRH kinase activity, and that AK can convert NRH into NAD⁺. In cultured cells and mouse liver, pharmacological or genetic inhibition of AK blocks formation of reduced nicotinamide mononucleotide (NMNH) and inhibits NRH-stimulated NAD⁺ biosynthesis. Finally, we confirm the presence of endogenous NRH in the liver with metabolomics. Our findings establish NRH as a natural precursor of NAD⁺ and reveal a new route for NAD⁺ biosynthesis via an NRH salvage pathway involving AK.

二氢神经酰胺酰胺（NRH）已被建议作为NAD ⁺合成的前体，但转化它的生化途径尚不清楚。在这里，我们显示NRH可以通过挽救途径转化为NAD ⁺，其中腺苷激酶（ADK，也称为AK）充当NRH激酶。使用同位素标记方法，我们证明NRH已完全整合到NAD ^+中，而NMNH作为中间体。我们进一步表明，AK富含NRH激酶活性的细胞裂解物中的馏分，并且AK可以将NRH转化为NAD ⁺。在培养的细胞和小鼠肝脏中，对AK的药理或遗传抑制作用可抑制还原的烟酰胺单核苷酸（NMNH）的形成并抑制NRH刺激的NAD。⁺生物合成。最后，我们用代谢组学证实了肝脏中内源性NRH的存在。我们的发现将NRH确立为NAD ⁺的天然前体，并揭示了通过涉及AK的NRH挽救途径进行NAD ⁺生物合成的新途径。