美国德克萨斯大学Gerta Hoxhaj团队揭示跨组织和跨肿瘤的从头嘌呤合成途径和嘌呤回收途径。2024年5月31日，《细胞》杂志在线发表了这项成果。

研究人员表示，嘌呤核苷酸对RNA和DNA合成、信号传递、新陈代谢和能量平衡至关重要。细胞合成嘌呤有两种主要途径：从头合成和回收途径。传统观点认为，增殖细胞主要依靠从头合成，而分化组织则偏向于回收途径。

意想不到的是，研究人员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循环前体，而次黄嘌呤在体内被迅速分解，回收率很低。定量代谢分析表明，在维持肿瘤中的嘌呤核苷酸池方面，从头合成和回收途径的贡献具有可比性。

值得注意的是，给小鼠喂食核苷酸会加速肿瘤生长，而抑制嘌呤回收则会减缓肿瘤进展，这揭示了回收途径在肿瘤代谢中的关键作用。这些发现从根本上揭示了正常组织和肿瘤是如何维持嘌呤核苷酸的，并强调了嘌呤回收在癌症中的重要作用。

附：英文原文

Title: De novo and salvage purine synthesis pathways across tissues and tumors

Author: Diem H. Tran, Dohun Kim, Rushendhiran Kesavan, Harrison Brown, Trishna Dey, Mona Hoseini Soflaee, Hieu S. Vu, Alpaslan Tasdogan, Jason Guo, Divya Bezwada, Houssam Al Saad, Feng Cai, Ashley Solmonson, Halie Rion, Rawand Chabatya, Salma Merchant, Nathan J. Manales, Vanina T. Tcheuyap, Megan Mulkey, Thomas P. Mathews, James Brugarolas, Sean J. Morrison, Hao Zhu, Ralph J. DeBerardinis, Gerta Hoxhaj

Issue&Volume: 2024-05-31

Abstract: Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, andenergy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantlyrely on de novo synthesis, whereas differentiated tissues favor the salvage pathway. Unexpectedly,we find that adenine and inosine are the most effective circulating precursors forsupplying purine nucleotides to tissues and tumors, while hypoxanthine is rapidlycatabolized 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 purinesalvage slows down tumor progression, revealing a crucial role of the salvage pathwayin tumor metabolism. These findings provide fundamental insights into how normal tissuesand tumors maintain purine nucleotides and highlight the significance of purine salvage in cancer.

DOI: 10.1016/j.cell.2024.05.011

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00520-8