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.

嘌呤核苷酸对于 RNA 和 DNA 合成、信号传导、代谢和能量稳态至关重要。为了合成嘌呤，细胞使用两种主要途径：从头途径和补救途径。传统上，人们认为增殖细胞主要依赖于从头合成，而分化的组织则倾向于挽救途径。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，而次黄嘌呤在体内被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挽救途径在维持肿瘤中嘌呤核苷酸库方面的相对贡献。值得注意的是，给小鼠喂食核苷酸会加速肿瘤生长，而抑制嘌呤补救会减缓肿瘤进展，揭示了补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，并强调了嘌呤挽救在癌症中的重要性。