Kanno T, Sudo K, Maekawa M, Nishimura Y, Ukita M, Fukutake K
Department of Laboratory Medicine, Hamamatsu University, Japan.
Clin Chim Acta. 1988 Mar 31;173(1):89-98. doi: 10.1016/0009-8981(88)90359-2.
Three families with a complete deficiency of the lactate dehydrogenase M subunit show exertional myoglobinuria. The response to ischemic forearm work is characteristic in these three families: an increase of venous lactate concentration after ischemic work was not observed and a marked increase of venous pyruvate was found. Glycolysis was markedly retarded in the patient's muscle in the glyceraldehyde 3-phosphate dehydrogenase (GA3PD) step. A significant increases in glyceraldehyde 3-phosphate, dihydroxyacetone phosphate and fructose 1,6-diphosphate were observed. The glycolysis retardation may be attributed to the impaired reoxidation of NADH produced by GA3PD action. The cytosolic fraction of skeletal muscle is rich in alpha-glycerophosphate dehydrogenase. This enzyme reoxidizes the excess NADH and drains triose phosphates from the glycolytic pathway under anaerobic conditions. For this reason, ATP production was significantly impaired and muscle cells were damaged in these patients. Consequently, the cytosolic enzymes and proteins such as creatine kinase and myoglobin were released into the blood stream. Otherwise, patients with a lactate dehydrogenase M-subunit deficiency do not show muscle stiffness and myoglobinuria under ordinary circumstances. They complain of muscle rigidity and sudden myoglobinuria after strenous exercise under anaerobic conditions. Thus, the lactate dehydrogenase M-subunit deficiency does not show any symptoms under ordinary circumstances, but is a latent hereditary disorder, now recognized as a new type of hereditary exertional myoglobinuria.
三个乳酸脱氢酶M亚基完全缺乏的家族出现运动性肌红蛋白尿。这三个家族对缺血性前臂运动的反应具有特征性：缺血运动后未观察到静脉乳酸浓度升高，却发现静脉丙酮酸显著升高。患者肌肉中的糖酵解在甘油醛3-磷酸脱氢酶（GA3PD）步骤明显受阻。观察到甘油醛3-磷酸、磷酸二羟丙酮和果糖1,6-二磷酸显著增加。糖酵解受阻可能归因于GA3PD作用产生的NADH再氧化受损。骨骼肌的胞质部分富含α-磷酸甘油脱氢酶。该酶在无氧条件下使过量的NADH再氧化，并从糖酵解途径中排出磷酸丙糖。因此，这些患者的ATP生成显著受损，肌肉细胞受到损伤。结果，肌酸激酶和肌红蛋白等胞质酶和蛋白质释放到血流中。否则，乳酸脱氢酶M亚基缺乏的患者在正常情况下不会出现肌肉僵硬和肌红蛋白尿。他们在无氧条件下剧烈运动后会抱怨肌肉僵硬和突然出现肌红蛋白尿。因此，乳酸脱氢酶M亚基缺乏在正常情况下不表现出任何症状，而是一种潜在的遗传性疾病，现在被认为是一种新型的遗传性运动性肌红蛋白尿。
