Regenerating liver uses ammonia to support de novo pyrimidine synthesis and cell proliferation
File version
Version of Record (VoR)
Author(s)
Kučera, Lukáš
Le, Dan-Diem Thi
Spinelli, Jessica B
Brožková, Andrea
Luptáková, Dominika
Klíma, Kryštof
Oliveira, Gabriela L
Brisudová, Petra
Boháčová, Klára
Boukalová, Štěpána
Zobalová, Renata
Kolář, František
Chalupsky, Karel
Dohnalová, Klára
et al.
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
Size
File type(s)
Location
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.
Journal Title
Nature Communications
Conference Title
Book Title
Edition
Volume
16
Issue
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Item Access Status
Note
Access the data
Related item(s)
Subject
Persistent link to this record
Citation
Endaya, BB; Kučera, L; Le, D-DT; Spinelli, JB; Brožková, A; Luptáková, D; Klíma, K; Oliveira, GL; Brisudová, P; Boháčová, K; Boukalová, Š; Zobalová, R; Kolář, F; Chalupsky, K; Dohnalová, K; et al., Regenerating liver uses ammonia to support de novo pyrimidine synthesis and cell proliferation, Nature Communications, 2025, 16, pp. 9664