김도훈 (University of Texas Southwestern Medical Center) | 한빛사논문 > 한빛사

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조회551

University of Texas Southwestern Medical Center

Cell, https://doi.org/10.1016/j.cell.2024.05.011 De novo and salvage purine synthesis pathways across tissues and tumors

Diem H. Tran,^1,5Dohun Kim,^1,5 Rushendhiran Kesavan,^1,5 Harrison Brown,¹ Trishna Dey,¹ Mona Hoseini Soflaee,¹ Hieu S. Vu,¹ Alpaslan Tasdogan,² Jason Guo,¹ Divya Bezwada,¹ Houssam Al Saad,¹ Feng Cai,¹ Ashley Solmonson,¹ Halie Rion,¹ Rawand Chabatya,¹ Salma Merchant,¹ Nathan J. Manales,¹ Vanina T. Tcheuyap,³ Megan Mulkey,¹ Thomas P. Mathews,¹ James Brugarolas,³ Sean J. Morrison,^1,4 Hao Zhu,¹ Ralph J. DeBerardinis,^1,4and Gerta Hoxhaj ^1,6,*

¹Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
²Department of Dermatology, University Hospital Essen & German Cancer Consortium, Partner Site, Essen, Germany
³Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA
⁴Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
⁵These authors contributed equally
⁶Lead contact

^*Corresponding author: correspondence to Gerta Hoxhaj

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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-06-04)
연구진국외 연구진
분야 생명과학 > 생화학

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