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Cited by 213Biochemical and Molecular ResearchAdenosine and Purinergic SignalingCancer, Hypoxia, and Metabolism

De novo and salvage purine synthesis pathways across tissues and tumors

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Tran, Diem H., Kim, Dohun, Kesavan, Rushendhiran, Brown, Harrison, Dey, Trishna, Soflaee, Mona Hoseini, Vu, Hieu S., Tasdogan, Alpaslan +17 more·2024·Cell
DOI 10.1016/j.cell.2024.05.011PMC PMC11246224
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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.

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  • Quiescent and differentiated cells preferentially utilize the salvage pathway, while highly proliferative cells depend more heavily on nucleotide biosynthesis.

    “While quiescent and differentiated cells preferentially utilize the salvage pathway, highly proliferative cells depend more heavily on nucleotide biosynthesis [79].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [79]

    The Introduction presents this contrast as a historical belief, not an established finding. The Discussion says the study challenges the notion that proliferating tumors predominantly rely on de novo synthesis: de novo and salvage pathways contribute similarly to their purine nucleotide pools. The cited paper therefore does not support stating the contrast as fact. (LLM, conf=0.88)

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Authors
Tran, D. H., Kim, D., Kesavan, R., Brown, H., Dey, T., Soflaee, M. H., Vu, H. S., Tasdogan, A., 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.
Affiliations
  • Children's Medical Center (US)
  • Essen University Hospital (DE)
  • Harold C. Simmons Comprehensive Cancer Center (US)
Corresponding author
Hoxhaj, Gerta
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2024-07
Volume
187
Issue
14
Pages
3602-3618.e20
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2024.05.011
PMC
PMC11246224
OpenAlex
W4399211695
Cited by
213
References
6
Citations by year
2026: 118 · 2025: 83 · 2024: 12
FWCI
27.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
Funders
  • V Foundation (V2021-019)
  • National Institutes of Health (RSG-22-177-01-TBE)
  • California Department of Fish and Game (467788900)
  • National Cancer Institute (1S10 RR029731-01, 1P30 CA142543-01, SCR_017949)
  • CPRIT (RR190087)
  • PEW Charitable Trusts
  • Deutsche Forschungsgemeinschaft
  • American Cancer Society (P50CA196516)
  • NIGMS (3R01GM143236-02S1)
  • Welch Foundation (I-2067-20210327)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
purine nucleotide metabolism, de novo purine synthesis, salvage pathway, cancer metabolism, adenine, inosine, tumor growth
MeSH terms
Adenine, Animals, Female, Humans, Inosine, Mice, Inbred C57BL, Neoplasms, Purine Nucleotides, Purines, Hypoxanthine, Cell Line, Tumor, Mice

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