Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Neuromuscul Disord. 2012 Dec;22 Suppl 3:S168-71. doi: 10.1016/j.nmd.2012.10.011.
Exertional fatigue early in exercise is a clinical hallmark of muscle glycogenoses, which is often coupled with painful muscle contractures and episodes of myoglobinuria. A fundamental biochemical problem in these conditions is the impaired generation of ATP to fuel muscle contractions, which relates directly to the metabolic defect, but also to substrate-limited energy deficiency, as exemplified by the "second wind" phenomenon in McArdle disease. A number of secondary events may also play a role in inducing premature fatigue in glycogenoses, including (1) absent or blunted muscle acidosis, which may be important for maintaining muscle membrane excitability by decreasing chloride permeability, (2) loss of the osmotic effect related to lactate accumulation, which may account for absence of the normal increase in water content of exercised muscle, and thus promote higher than normal concentrations of extracellular potassium in exercising muscle and (3) exaggerated accumulation of ADP during exercise that may inhibit sodium-potassium and calcium-ATPases. Disorders of muscle glycogenolysis and glycolysis reveal the crucial role of these metabolic processes for supplying both anaerobic and aerobic energy for muscle contraction; and the pathological fatigue that occurs when glycogenolysis and/or glycolysis is blocked imply an important role for theses metabolic pathways in normal muscle fatigue.
运动早期的劳累是肌肉糖原贮积症的一个临床特征，常伴有肌肉痛性痉挛和肌红蛋白尿。这些病症的一个基本生化问题是生成供肌肉收缩的 ATP 的能力受损，这与代谢缺陷直接相关，也与底物限制型能量缺乏有关，如 McArdle 病的“第二次呼吸”现象。一些次要事件也可能在诱导糖原贮积症的过早疲劳中起作用，包括（1）缺乏或减弱的肌肉酸中毒，这可能通过降低氯离子通透性来维持肌肉膜兴奋性，（2）与乳酸堆积相关的渗透压丧失，这可能解释了运动肌肉正常含水量的增加的缺失，从而促进运动肌肉中高于正常浓度的细胞外钾，以及（3）运动期间 ADP 的过度积累，这可能抑制钠钾和钙 ATP 酶。肌肉糖原分解和糖酵解的紊乱揭示了这些代谢过程为肌肉收缩提供无氧和有氧能量的关键作用；当糖原分解和/或糖酵解受阻时发生的病理性疲劳意味着这些代谢途径在正常肌肉疲劳中起着重要作用。
