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Simple oxygraphic analysis for the presence of adenylate kinase 1 and 2 in normal and tumor cells

Abstract : Background: Chronic obstructive pulmonary disease (COPD) is characterized by the inability of patients to sustain a high level of ventilation resulting in perceived exertional discomfort and limited exercise capacity of leg muscles at average intracellular ATP levels sufficient to support contractility. Methods: Myosin ATPase activity in biopsy samples from healthy and COPD individuals was implemented as a local nucleotide sensor to determine ATP diffusion coefficientswithin myofibrils. Ergometric parameters clinically measured during maximal exercise tests in both groups were used to define the rates of myosin ATPase reaction and aerobic ATP re-synthesis. The obtained parameters in combinationwith AK- and CK-catalyzed reactions were implemented to compute the kinetic and steady-state spatial ATP distributions within control and COPD sarcomeres. Results: The developed reaction–diffusionmodel of two-dimensional sarcomeric space identified similar, yet extremely low nucleotide diffusion in normal and COPD myofibrils. The corresponding spatio-temporal ATP distributions, constructed during imposed exercise, predicted in COPD sarcomeres a depletion of ATP in the zones of overlap between actin and myosin filaments along the center axis at average cytosolic ATP levels similar to healthy muscles. Conclusions: ATP-depleted zones can induce rigor tension foci impairing muscle contraction and increase a risk for sarcomere damages. Thus, intra-sarcomeric diffusion restrictions at limited aerobic ATP re-synthesis can be an additional risk factor contributing to the muscle contractile deficiency experienced by COPD patients. General significance: This study demonstrates how restricted substrate mobility within a cellular organelle can provoke an energy imbalance state paradoxically occurring at abounding average metabolic resources.
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Contributeur : Sarah Hamant <>
Soumis le : lundi 19 novembre 2018 - 15:42:30
Dernière modification le : mardi 28 juillet 2020 - 03:02:21





Aleksandr Klepinin, Lyudmila Ounpuu, Rita Guzun, Vladimir Chekulayev, Natalja Timohhina, et al.. Simple oxygraphic analysis for the presence of adenylate kinase 1 and 2 in normal and tumor cells. Journal of Bioenergetics and Biomembranes, Springer Verlag, 2016, 48 (5), pp.531 - 548. ⟨10.1007/s10863-016-9687-3⟩. ⟨hal-01927039⟩



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