IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-65451-2.html
   My bibliography  Save this article

Regenerating liver uses ammonia to support de novo pyrimidine synthesis and cell proliferation

Author

Listed:
  • Berwini B. Endaya

    (Czech Academy of Sciences
    Charles University
    Charles University)

  • Lukáš Kučera

    (Academy of Sciences of the Czech Republic)

  • Dan-Diem Thi Le

    (Czech Academy of Sciences
    Charles University)

  • Jessica B. Spinelli

    (University of Massachusetts)

  • Andrea Brožková

    (Charles University)

  • Dominika Luptáková

    (Czech Academy of Sciences)

  • Kryštof Klíma

    (Academy of Sciences of the Czech Republic)

  • Gabriela L. Oliveira

    (Czech Academy of Sciences
    University of Coimbra
    University of Coimbra
    University of Coimbra)

  • Petra Brisudová

    (Czech Academy of Sciences)

  • Klára Boháčová

    (Czech Academy of Sciences)

  • Štěpána Boukalová

    (Czech Academy of Sciences)

  • Renata Zobalová

    (Czech Academy of Sciences)

  • František Kolář

    (Czech Academy of Sciences)

  • Karel Chalupsky

    (Academy of Sciences of the Czech Republic)

  • Klára Dohnalová

    (Academy of Sciences of the Czech Republic)

  • Arash Yarmohammadi-Barzegar

    (Charles University)

  • Šárka Dvořáková

    (Czech Academy of Sciences)

  • Evgeniya Biryukova

    (Academy of Sciences of the Czech Republic)

  • Marta Kaliaeva

    (Academy of Sciences of the Czech Republic)

  • Vladimír Havlíček

    (Czech Academy of Sciences
    Palacký University)

  • Radislav Sedláček

    (Academy of Sciences of the Czech Republic)

  • Jan Procházka

    (Academy of Sciences of the Czech Republic)

  • Libor Vítek

    (Charles University
    General University Hospital)

  • Sunghyouk Park

    (Seoul National University)

  • Pavel Martásek

    (Charles University
    General University Hospital)

  • Zdeněk Krška

    (Charles University
    General University Hospital)

  • Paulo J. Oliveira

    (University of Coimbra
    University of Coimbra)

  • Michael V. Berridge

    (Kelburn)

  • Jiří Neužil

    (Czech Academy of Sciences
    Charles University
    Charles University
    Griffith University)

Abstract

Liver is endowed with high regenerative activity, so that the tissue regrows in mouse after partial hepatectomy within days. We reason that this requires de novo pyrimidine synthesis to support rapid progression via the cell cycle. We find that suppression of de novo pyrimidine synthesis prevents proliferation in regenerating liver, suppressing liver regrowth. Tracing studies and spatial metabolomics reveal a metabolic shift such that ammonia, normally detoxified to urea in the periportal region under homeostasis, is redirected for generating aspartate and carbamoyl phosphate periportally, and glutamine pericentrally, and these products are utilized as precursors by the de novo pyrimidine synthesis pathway. Our research uncovers a metabolic reprogramming leading to utilization of a toxic byproduct for anabolic pathways that are essential for liver regeneration.

Suggested Citation

  • Berwini B. Endaya & Lukáš Kučera & Dan-Diem Thi Le & Jessica B. Spinelli & Andrea Brožková & Dominika Luptáková & Kryštof Klíma & Gabriela L. Oliveira & Petra Brisudová & Klára Boháčová & Štěpána Bouk, 2025. "Regenerating liver uses ammonia to support de novo pyrimidine synthesis and cell proliferation," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65451-2
    DOI: 10.1038/s41467-025-65451-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-65451-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-65451-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jiyeon Kim & Zeping Hu & Ling Cai & Kailong Li & Eunhee Choi & Brandon Faubert & Divya Bezwada & Jaime Rodriguez-Canales & Pamela Villalobos & Yu-Fen Lin & Min Ni & Kenneth E. Huffman & Luc Girard & L, 2017. "CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells," Nature, Nature, vol. 546(7656), pages 168-172, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Christopher W. Murray & Jennifer J. Brady & Mingqi Han & Hongchen Cai & Min K. Tsai & Sarah E. Pierce & Ran Cheng & Janos Demeter & David M. Feldser & Peter K. Jackson & David B. Shackelford & Monte M, 2022. "LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Leandro R. Soria & Georgios Makris & Alfonso M. D’Alessio & Angela Angelis & Iolanda Boffa & Veronica M. Pravata & Véronique Rüfenacht & Sergio Attanasio & Edoardo Nusco & Paola Arena & Andrew T. Fere, 2022. "O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65451-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.