Verrill H L, Gruemer H D, Baba N
Clin Chem. 1977 Dec;23(12):2226-30.
A defective membrane mechanism has been suggested [Arch. Neurol. 33, 315 (1976)] for the pathogenesis of Duchenne muscular dystrophy. The characteristic clinical and biological findings, including leakage of cellular enzymes into the serum in the disease, have been duplicated by the imipramine/serotonin rat myopathy model. Sarcolemma was prepared from quadriceps femoris muscles of control and myopathy-affected animals. The activities of sarcolemmal adenosinetriphosphatase and acetylcholinesterase were inhibited in vitro by imipramine and serotonin. The inhibition by imipramine of these sarcolemma-bound enzyme systems decreased the Vmax and increased the Km. This mixed type of inhibition is consistent with an imipramine-induced interference at these enzyme sites and a disruption of lipid-protein interrelations. We hypothesize that such conformational membrane changes might contribute to the leakage of macromolecules such as enzymes from the cell interior.
对于杜氏肌营养不良症的发病机制，有人提出了一种有缺陷的膜机制[《神经病学档案》33, 315 (1976)]。丙咪嗪/血清素大鼠肌病模型复制了该疾病的特征性临床和生物学表现，包括细胞内酶泄漏到血清中。从对照动物和患肌病动物的股四头肌制备肌膜。丙咪嗪和血清素在体外抑制了肌膜腺苷三磷酸酶和乙酰胆碱酯酶的活性。丙咪嗪对这些与肌膜结合的酶系统的抑制降低了最大反应速度（Vmax）并增加了米氏常数（Km）。这种混合型抑制与丙咪嗪在这些酶位点诱导的干扰以及脂 - 蛋白相互关系的破坏是一致的。我们推测，这种膜构象变化可能导致酶等大分子从细胞内部泄漏。
