Journal Article

DKFZ-2024-01170

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png De novo and salvage purine synthesis pathways across tissues and tumors.

Tran, D. H. ; Kim, D. ; Kesavan, R. ; Brown, H. ; Dey, T. ; Soflaee, M. H. ; Vu, H. S. ; Tasdogan, A.DKFZ* ; Guo, J. ; Bezwada, D. ; Al Saad, H. ; Cai, F. ; Solmonson, A. ; Rion, H. ; Chabatya, R. ; Merchant, S. ; Manales, N. J. ; Tcheuyap, V. T. ; Mulkey, M. ; Mathews, T. P. ; Brugarolas, J. ; Morrison, S. J. ; Zhu, H. ; DeBerardinis, R. J. ; Hoxhaj, G.

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.cell.2024.05.011

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.

Keyword(s): cancer metabolism ; de novo purine synthesis ; in vivo isotope tracing ; nucleotide diet ; nucleotide metabolism ; purine bases ; purine degradation ; purine salvage ; tissue ; tumor growth

Note: 2024 Jul 11;187(14):3602-3618.e20

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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