2022
DOI: 10.3390/biomedicines10051199
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Robustness of the Krebs Cycle under Physiological Conditions and in Cancer: New Clues for Evaluating Metabolism-Modifying Drug Therapies

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 in… Show more

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Cited by 2 publications
(8 citation statements)
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References 56 publications
(65 reference statements)
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“…The need of fast-acting regulation mechanisms in mitochondria TCA cycle is very robust and has inertia; the concentration of cycle intermediates is accommodated to keep the flux with little variations. [7] The cycle is both anabolic and catabolic and, therefore, there are reactions that produce metabolites of the cycle and reactions that extract metabolites from it, they are known as anaplerotic reactions. In muscle mitochondria, during exercise, fumarate supply from an anaplerotic reaction and increased availability of acetyl-CoA lead to a significant increase in cycle flux, when the muscle stops working, the initial steady state is progressively restored.…”
Section: Hormonal-like Regulation Of the Krebs Cyclementioning
confidence: 99%
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“…The need of fast-acting regulation mechanisms in mitochondria TCA cycle is very robust and has inertia; the concentration of cycle intermediates is accommodated to keep the flux with little variations. [7] The cycle is both anabolic and catabolic and, therefore, there are reactions that produce metabolites of the cycle and reactions that extract metabolites from it, they are known as anaplerotic reactions. In muscle mitochondria, during exercise, fumarate supply from an anaplerotic reaction and increased availability of acetyl-CoA lead to a significant increase in cycle flux, when the muscle stops working, the initial steady state is progressively restored.…”
Section: Hormonal-like Regulation Of the Krebs Cyclementioning
confidence: 99%
“…A recent paper shows that the TCA cycle has inertia and is robust in the sense that it is prone to attain a new steady state with simple adjustment of metabolite concentrations and limited changes in flux. [7] If only the activity of one enzyme of the TCA cycle increases/decreases, the change in flux is usually low unless other parameters change substantially, for example, ADP/ATP ratio, NAD + /NADH ratio and/or acetyl-CoA supply/concentration. In a given circumstance TCA cycle is in steady state, that is, both the flux and the concentrations of metabolites of the TCA cycle remain constant.…”
Section: Tca Cycle Balancementioning
confidence: 99%
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