Kanno T, Sudo K, Kitamura M, Miwa S, Ichiyama A, Nishimura Y
Isozymes Curr Top Biol Med Res. 1983;7:131-50.
Different clinical features exist for lactate dehydrogenase A-subunit and B-subunit deficiencies. The metabolic basis for these clinical differences was elucidated by investigating carbohydrate metabolism in the affected tissues. Glycolysis was markedly retarded at the position of glyceraldehyde 3-phosphate dehydrogenase, and significant increases of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-diphosphate were observed. The physical and kinetic properties of glyceraldehyde 3-phosphate dehydrogenase prepared from human erythrocytes and skeletal muscle were almost identical, but the mode of inhibition of the enzyme was slightly different in erythrocytes and in skeletal muscle. In erythrocytes, impaired reoxidation of NADH followed by the deficiency of substrate NAD+ causes a reduction of glyceraldehyde 3-phosphate dehydrogenase activity. However, in skeletal muscle, the increased level of NADH markedly inhibits the enzyme under anaerobic conditions. A flux of triose phosphates from glycolysis occurred in skeletal muscle of a patient with A-subunit deficiency. This flux is attributable to the high cytosol alpha-glycerophosphate dehydrogenase activity in skeletal muscle. for these reasons the ATP production was significantly impaired in the patient and the damage to muscle cells brings about the release of cytosolic enzymes and muscle rigidity after hard exercise. In contrast in the erythrocytes, the level of alpha-glycerophosphate dehydrogenase is very low and another red cell-specific NADH reoxidizing system such as NADH-cytochrome b5 reductase (NADH-methemoglobin reductase) is operating. In this manner, the NAD+ level in erythrocytes is compensated for without the flux of triose phosphates derived from glucose. Therefore, the ATP production in erythrocytes is sufficiently maintained by glycolysis even in a patient with complete lactate dehydrogenase B-subunit deficiency. Thus, impaired ATP production in anaerobic stage is a condition which is specific for lactate dehydrogenase A-subunit deficiency but does not occur for B-subunit deficiency. The different clinical features of the A- and B-subunit deficiencies have been clearly elucidated.
乳酸脱氢酶A亚基和B亚基缺乏具有不同的临床特征。通过研究受影响组织中的碳水化合物代谢，阐明了这些临床差异的代谢基础。糖酵解在甘油醛-3-磷酸脱氢酶位置明显受阻，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。从人红细胞和骨骼肌制备的甘油醛-3-磷酸脱氢酶的物理和动力学性质几乎相同，但该酶在红细胞和骨骼肌中的抑制模式略有不同。在红细胞中，NADH再氧化受损，随后底物NAD+缺乏导致甘油醛-3-磷酸脱氢酶活性降低。然而，在骨骼肌中，NADH水平升高在无氧条件下显著抑制该酶。在A亚基缺乏的患者骨骼肌中，发生了来自糖酵解的磷酸丙糖通量。这种通量归因于骨骼肌中高细胞质α-磷酸甘油脱氢酶活性。由于这些原因，患者的ATP产生显著受损，剧烈运动后肌肉细胞损伤导致细胞质酶释放和肌肉僵硬。相比之下，在红细胞中，α-磷酸甘油脱氢酶水平非常低，另一种红细胞特异性NADH再氧化系统如NADH-细胞色素b5还原酶（NADH-高铁血红蛋白还原酶）在起作用。通过这种方式，红细胞中的NAD+水平得到补偿，而无需来自葡萄糖的磷酸丙糖通量。因此，即使在完全缺乏乳酸脱氢酶B亚基的患者中，红细胞中的ATP产生也通过糖酵解得到充分维持。因此，无氧阶段ATP产生受损是乳酸脱氢酶A亚基缺乏特有的情况，而B亚基缺乏则不会发生。A亚基和B亚基缺乏的不同临床特征已得到明确阐明。
