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001     290573
005     20250820105758.0
024 7 _ |a 10.1016/j.cell.2024.05.011
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024 7 _ |a pmid:38823389
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024 7 _ |a 0092-8674
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024 7 _ |a 1097-4172
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041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Tran, Diem H
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245 _ _ |a De novo and salvage purine synthesis pathways across tissues and tumors.
260 _ _ |a New York, NY
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336 7 _ |a article
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500 _ _ |a 2024 Jul 11;187(14):3602-3618.e20
520 _ _ |a 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.
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650 _ 7 |a cancer metabolism
|2 Other
650 _ 7 |a de novo purine synthesis
|2 Other
650 _ 7 |a in vivo isotope tracing
|2 Other
650 _ 7 |a nucleotide diet
|2 Other
650 _ 7 |a nucleotide metabolism
|2 Other
650 _ 7 |a purine bases
|2 Other
650 _ 7 |a purine degradation
|2 Other
650 _ 7 |a purine salvage
|2 Other
650 _ 7 |a tissue
|2 Other
650 _ 7 |a tumor growth
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700 1 _ |a Kim, Dohun
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700 1 _ |a Kesavan, Rushendhiran
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700 1 _ |a Brown, Harrison
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700 1 _ |a Dey, Trishna
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700 1 _ |a Soflaee, Mona Hoseini
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700 1 _ |a Vu, Hieu S
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700 1 _ |a Tasdogan, Alpaslan
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700 1 _ |a Guo, Jason
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700 1 _ |a Bezwada, Divya
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700 1 _ |a Al Saad, Houssam
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700 1 _ |a Cai, Feng
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700 1 _ |a Solmonson, Ashley
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700 1 _ |a Rion, Halie
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700 1 _ |a Chabatya, Rawand
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700 1 _ |a Merchant, Salma
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700 1 _ |a Manales, Nathan J
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700 1 _ |a Tcheuyap, Vanina T
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700 1 _ |a Mulkey, Megan
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700 1 _ |a Mathews, Thomas P
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700 1 _ |a Brugarolas, James
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700 1 _ |a Morrison, Sean J
|b 21
700 1 _ |a Zhu, Hao
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700 1 _ |a DeBerardinis, Ralph J
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700 1 _ |a Hoxhaj, Gerta
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773 _ _ |a 10.1016/j.cell.2024.05.011
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856 4 _ |u https://inrepo02.dkfz.de/record/290573/files/1-s2.0-S0092867424005208-main.pdf
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