TY  - JOUR
AU  - Tran, Diem H
AU  - Kim, Dohun
AU  - Kesavan, Rushendhiran
AU  - Brown, Harrison
AU  - Dey, Trishna
AU  - Soflaee, Mona Hoseini
AU  - Vu, Hieu S
AU  - Tasdogan, Alpaslan
AU  - Guo, Jason
AU  - Bezwada, Divya
AU  - Al Saad, Houssam
AU  - Cai, Feng
AU  - Solmonson, Ashley
AU  - Rion, Halie
AU  - Chabatya, Rawand
AU  - Merchant, Salma
AU  - Manales, Nathan J
AU  - Tcheuyap, Vanina T
AU  - Mulkey, Megan
AU  - Mathews, Thomas P
AU  - Brugarolas, James
AU  - Morrison, Sean J
AU  - Zhu, Hao
AU  - DeBerardinis, Ralph J
AU  - Hoxhaj, Gerta
TI  - De novo and salvage purine synthesis pathways across tissues and tumors.
JO  - Cell
VL  - 187
IS  - 14
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-01170
SP  - 3602-3618.e20
PY  - 2024
N1  - 2024 Jul 11;187(14):3602-3618.e20
AB  - 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.
KW  - cancer metabolism (Other)
KW  - de novo purine synthesis (Other)
KW  - in vivo isotope tracing (Other)
KW  - nucleotide diet (Other)
KW  - nucleotide metabolism (Other)
KW  - purine bases (Other)
KW  - purine degradation (Other)
KW  - purine salvage (Other)
KW  - tissue (Other)
KW  - tumor growth (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38823389
DO  - DOI:10.1016/j.cell.2024.05.011
UR  - https://inrepo02.dkfz.de/record/290573
ER  -