Česká společnost pro hmotnostní spektrometrii

(13. ročník České konference hmotnostní spektrometrie a 11. Neformální proteomické setkání - FrO-16)
Spatial mapping of 15N-labeled ammonia with MALDI-FTICR imaging in regenerating liver tissue: Re-directing of toxic byproduct into anabolic pathways

Lukáš Kučera ^1 *, Berwini B. Endaya ^2,3, Dominika Luptáková ⁴, Kryštof Klíma ¹, Vladimír Havlíček ⁴, Radislav Sedláček ¹, Jan Procházka ¹, Jiří Neužil ^2,5

1. Institute of Molecular genetics, AV ČR, Prague, Czech Republic
2. Institute of Biotechnology, Czech Academy of Sciences, Prague-West, Czech Republic
3. Faculty of Science, Charles University, Prague 2, Czech Republic;
4. Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic
5. School of Pharmacy and Medical Science, Griffith University, Southport, Qld, Australia

Abstrakt

Liver is endowed with high regenerative activity, such that the tissue will regrow in the mouse after partial hepatectomy within days. We reasoned that this requires de novo pyrimidine synthesis to support rapid progression via the cell cycle. With MALDI imaging technique we revealed that suppression of de novo pyrimidine synthesis prevents proliferation in regenerating liver, suppressing liver regrowth. Tracing studies and spatial metabolomics revealed 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. This study uncovers a metabolic reprogramming leading to utilization of a toxic byproduct for anabolic pathways that are essential for liver regeneration.

* Korespondující autor: j.neuzil@griffith.edu.au