Ponsot E, Zoll J, N'guessan B, Ribera F, Lampert E, Richard R, Veksler V, Ventura-Clapier R, Mettauer B
Service des Explorations Fonctionnelles Respiratoires et de l'Exercice, Département de Physiologie, Strasbourg, France.
J Cell Physiol. 2005 Jun;203(3):479-86. doi: 10.1002/jcp.20245.
As energetic metabolism is crucial for muscles, they develop different adaptations to respond to fluctuating demand among muscle types. Whereas quantitative characteristics are known, no study described simultaneously quantitative and qualitative differences among muscle types in terms of substrates utilization patterns. This study thus defined the pattern of substrates preferential utilization by mitochondria from glycolytic gastrocnemius (GAS) and oxidative soleus (SOL) skeletal muscles and from heart left ventrical (LV) in rats. We measured in situ, ADP (2 mM)-stimulated, mitochondrial respiration rates from skinned fibers in presence of increasing concentrations of pyruvate (Pyr) + malate (Mal), palmitoyl-carnitine (Palm-C) + Mal, glutamate (Glut) + Mal, glycerol-3-phosphate (G3-P), lactate (Lact) + Mal. Because the fibers oxygen uptake (Vs) followed Michaelis-Menten kinetics in function of substrates level we determined the Vs and Km, representing maximal oxidative capacity and the mitochondrial sensibility for each substrate, respectively. Vs were in the order GAS < SOL < LV for Pyr, Glu, and Palm-C substrates, whereas in the order SOL = LV < GAS with G3-P. Moreover, the relative capacity to oxidize Palm-C is extremely higher in LV than in SOL. Vs was not stimulated by the Lact substrate. The Km was equal for Pyr among muscles, but much lower for G3-P in GAS and lower for Palm-C in LV. These results demonstrate qualitative mitochondrial tissue specificity for metabolic pathways. Mitochondria of glycolytic muscle fibers are well adapted to play a central role for maintaining a satisfactory cytosolic redox state in these fibers, whereas mitochondria of LV developed important capacities to use fatty acids.
由于能量代谢对肌肉至关重要，它们会产生不同的适应性变化以应对不同肌肉类型间波动的需求。虽然已知一些定量特征，但尚无研究同时描述不同肌肉类型在底物利用模式方面的定量和定性差异。因此，本研究确定了大鼠糖酵解型腓肠肌（GAS）、氧化型比目鱼肌（SOL）和心脏左心室（LV）中线粒体底物优先利用的模式。我们在离体条件下，在存在递增浓度的丙酮酸（Pyr）+苹果酸（Mal）、棕榈酰肉碱（Palm-C）+Mal、谷氨酸（Glut）+Mal、甘油-3-磷酸（G3-P）、乳酸（Lact）+Mal的情况下，测量了经皮纤维在2 mM ADP刺激下的线粒体呼吸速率。由于纤维的氧摄取量（Vs）随底物水平呈米氏动力学变化，我们分别测定了Vs和Km，它们分别代表每种底物的最大氧化能力和线粒体敏感性。对于Pyr、Glu和Palm-C底物，Vs的顺序为GAS < SOL < LV，而对于G3-P，顺序为SOL = LV < GAS。此外，LV氧化Palm-C的相对能力比SOL极高。Lact底物未刺激Vs。肌肉间Pyr的Km相等，但GAS中G3-P的Km低得多，LV中Palm-C的Km较低。这些结果证明了线粒体组织在代谢途径上的定性特异性。糖酵解型肌纤维的线粒体非常适合在维持这些纤维中令人满意的胞质氧化还原状态方面发挥核心作用，而LV的线粒体则发展出了利用脂肪酸的重要能力。
