Ammonia plays an important role in cellular metabolism. However, ammonia is considered a toxic product. In bone marrow-derived mesenchymal stem cells, multipotent stem cells with high expression of glutamine synthetase (GS) in bone marrow, ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs. As a major nutritional amino acid for biosynthesis, glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation. The activation of mTOR can promote cell entry into S phase, thereby enhancing DNA synthesis and cell proliferation. Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity. Then, the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation. These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.

氨在细胞代谢中起着重要作用。然而，氨被认为是有毒产品。在骨髓来源的间充质干细胞中，骨髓中谷氨酰胺合成酶（GS）高表达的多能干细胞，氨和谷氨酸可以通过谷氨酰胺合成酶活性转化为谷氨酰胺，支持MSC的增殖。谷氨酰胺作为生物合成的主要营养氨基酸，可以激活 Akt/mTOR/S6k 通路，刺激细胞增殖。 mTOR的激活可以促进细胞进入S期，从而增强DNA合成和细胞增殖。我们的研究表明，间充质干细胞可以通过 GS 活性将有毒废物氨转化为营养性谷氨酰胺。然后，Akt/mTOR/S6k通路被激活，促进骨髓间充质干细胞增殖。这些结果提出了治疗高氨血症疾病的新治疗策略和潜在靶点。