Files
Document type
ArticleVersion
Published versionPublication date
Publication license
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/186035
Robustness of the Krebs Cycle under Physiological Conditions and in Cancer: New Clues for Evaluating Metabolism-Modifying Drug Therapies
Journal Title
Director/Tutor
Journal ISSN
Volume Title
Related resource
Abstract
The Krebs cycle in cells that contain mitochondria is necessary for both energy production and anabolic processes. In given cell/condition, the Krebs cycle is dynamic but remains at a steady state. In this article, we first aimed at comparing the properties of a closed cycle versus the same metabolism in a linear array. The main finding is that, unlike a linear metabolism, the closed cycle can reach a steady state (SS) regardless of the nature and magnitude of the disturbance. When the cycle is modeled with input and output reactions, the 'open' cycle is robust and reaches a steady state but with exceptions that lead to sustained accumulation of intermediate metabolites, i.e., conditions at which no SS can be achieved. The modeling of the cycle in cancer, trying to obtain marked reductions in flux, shows that these reductions are limited and therefore the Warburg effect is moderate at most. In general, our results of modeling the cycle in different conditions and looking for the achievement, or not, of SS, suggest that the cycle may have a regulation, not yet discovered, to go from an open cycle to a closed one. Said regulation could allow for reaching the steady state, thus avoiding the unwanted effects derived from the aberrant accumulation of metabolites in the mitochondria. The information in this paper might be useful to evaluate metabolism-modifying medicines.
Subject
Subject (English)
Citation
Citation
FRANCO FERNÁNDEZ, Rafael and SERRANO-MARÍN, Joan. Robustness of the Krebs Cycle under Physiological Conditions and in Cancer: New Clues for Evaluating Metabolism-Modifying Drug Therapies. Biomedicines. 2022. Vol. 10, num. 5, pags. 1-14. ISSN 2227-9059. [consulted: 10 of June of 2026]. Available at: https://hdl.handle.net/2445/186035