Ammonia is a ubiquitous by-product of cellular metabolism; however, the biological consequences of ammonia production are not fully understood, especially in cancer. We found that ammonia is not merely a toxic waste product but is recycled into central amino acid metabolism to maximize nitrogen utilization. In our experiments, human breast cancer cells primarily assimilated ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH); secondary reactions enabled other amino acids, such as proline and aspartate, to directly acquire this nitrogen. Metabolic recycling of ammonia accelerated proliferation of breast cancer. In mice, ammonia accumulated in the tumor microenvironment and was used directly to generate amino acids through GDH activity. These data show that ammonia is not only a secreted waste product but also a fundamental nitrogen source that can support tumor biomass.

中文翻译：

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通过谷氨酸脱氢酶进行氨的代谢循环可支持乳腺癌生物量

氨是细胞新陈代谢的普遍产物。然而，氨生产的生物学后果尚未得到充分了解，尤其是在癌症中。我们发现氨不仅是有毒的废物，而且还被循环利用到中央氨基酸代谢过程中，以最大限度地利用氮。在我们的实验中，人类乳腺癌细胞主要通过谷氨酸脱氢酶（GDH）催化的还原胺化作用吸收氨。二次反应使其他氨基酸（例如脯氨酸和天冬氨酸）能够直接获取该氮。氨的代谢循环加速了乳腺癌的扩散。在小鼠中，氨在肿瘤微环境中积累，并通过GDH活性直接用于产生氨基酸。