Siharath Camille, Biondi Olivier, Peres Sabine
Laboratoire de Biométrie et de Biologie Évolutive, UMR CNRS 5558 Université Claude Bernard Lyon 1, 69622, Villeurbanne cedex, France.
ERABLE, INRIA Lyon Centre, 69622, Villeurbanne cedex, France.
Heliyon. 2024 Dec 9;10(24):e40918. doi: 10.1016/j.heliyon.2024.e40918. eCollection 2024 Dec 30.
Biological modelling helps understanding complex processes, like energy metabolism, by predicting pathway compensations and equilibrium under given conditions. When deciphering metabolic adaptations, traditional experiments face challenges due to numerous enzymatic activities, needing modelling to anticipate pathway behaviours and orientate research. This paper aims to implement a constraint-based modelling method of muscular energy metabolism, adaptable to individual situations, energy demands, and complex disease-specific metabolic alterations like muscular dystrophy calpainopathy. Our calpainopathy-like model not only confirms the ATP production defect under increasing energy demands, but suggests compensatory mechanisms through anaerobic glycolysis. However, excessive glycolysis indicates a need to enhance mitochondrial respiration, preventing excess lactate production common in several diseases. Our model suggests that moderate-intensity physiotherapy, known to improve aerobic performance and anaerobic buffering, combined with increased carbohydrate and amino acid sources, could be a potent therapeutic approach for calpainopathy.
生物建模有助于通过预测给定条件下的途径补偿和平衡来理解复杂的过程,如能量代谢。在解读代谢适应性时,由于存在众多酶活性,传统实验面临挑战,需要建模来预测途径行为并指导研究。本文旨在实施一种基于约束的肌肉能量代谢建模方法,该方法适用于个体情况、能量需求以及诸如肌肉萎缩性钙蛋白酶病等复杂疾病特异性代谢改变。我们的类钙蛋白酶病模型不仅证实了在能量需求增加时ATP产生缺陷,还通过无氧糖酵解提出了补偿机制。然而,过度糖酵解表明需要增强线粒体呼吸,以防止在几种疾病中常见的过量乳酸产生。我们的模型表明,已知能改善有氧性能和无氧缓冲的中等强度物理治疗,结合增加碳水化合物和氨基酸来源,可能是治疗钙蛋白酶病的有效方法。