Abstract：
Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, and energy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantly rely on de novo synthesis, whereas differentiated tissues favor the salvage pathway. Unexpectedly, we find that adenine and inosine are the most effective circulating precursors for supplying purine nucleotides to tissues and tumors, while hypoxanthine is rapidly catabolized and poorly salvaged in vivo. Quantitative metabolic analysis demonstrates comparative contribution from de novo synthesis and salvage pathways in maintaining purine nucleotide pools in tumors. Notably, feeding mice nucleotides accelerates tumor growth, while inhibiting purine salvage slows down tumor progression, revealing a crucial role of the salvage pathway in tumor metabolism. These findings provide fundamental insights into how normal tissues and tumors maintain purine nucleotides and highlight the significance of purine salvage in cancer.
摘要：
嘌呤核苷酸对于RNA和DNA合成至关重要,信令,新陈代谢，和能量稳态。要合成嘌呤，细胞使用两种主要途径:从头途径和救助途径。传统上,据认为，增殖细胞主要依赖于从头合成，而分化的组织倾向于挽救途径。出乎意料的是,我们发现腺嘌呤和肌苷是向组织和肿瘤提供嘌呤核苷酸的最有效的循环前体，而次黄嘌呤在体内快速分解代谢且回收不良。定量代谢分析证明了从头合成和补救途径在维持肿瘤中嘌呤核苷酸库方面的比较贡献。值得注意的是,喂食小鼠核苷酸加速肿瘤生长，而抑制嘌呤挽救减缓肿瘤进展，揭示了挽救途径在肿瘤代谢中的关键作用。这些发现为正常组织和肿瘤如何维持嘌呤核苷酸提供了基本见解，并强调了嘌呤补救在癌症中的重要性。
