De novo and salvage purine synthesis pathways across tissues and tumors.

Autor:	Tran DH; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Kim D; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Kesavan R; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Brown H; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Dey T; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Soflaee MH; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Vu HS; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Tasdogan A; Department of Dermatology, University Hospital Essen & German Cancer Consortium, Partner Site, Essen, Germany., Guo J; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Bezwada D; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Al Saad H; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Cai F; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Solmonson A; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Rion H; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Chabatya R; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Merchant S; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Manales NJ; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Tcheuyap VT; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Mulkey M; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Mathews TP; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Brugarolas J; Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Morrison SJ; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Zhu H; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., DeBerardinis RJ; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Hoxhaj G; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: gerta.hoxhaj@utsouthwestern.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Jul 11; Vol. 187 (14), pp. 3602-3618.e20. Date of Electronic Publication: 2024 May 31.
DOI:	10.1016/j.cell.2024.05.011
Abstrakt:	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. Competing Interests: Declaration of interests R.J.D. is an advisor for Agios Pharmaceuticals and Vida Ventures. S.J.M. is an advisor for Frequency Therapeutics and Protein Fluidics, as well as a stockholder in G1 Therapeutics and Mereo Biopharma. H.Z. has a sponsored research agreement with Alnylam Pharmaceuticals, consults for Flagship Pioneering and Chroma Medicines, and serves on the SAB of Ubiquitix. J.B. is an employee/paid consultant for Arrowhead, Calithera, Esai, Exelixis, and Johnson & Johnson and reports receiving commercial research grants from Arrowhead. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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