Hinman L M, Sheu K F, Baker A C, Kim Y T, Blass J P
Department of Neurology, Cornell University Medical College, Burke Rehabilitation Center, White Plains, NY.
Neurology. 1989 Jan;39(1):70-5. doi: 10.1212/wnl.39.1.70.
Several groups have reported abnormalities of the pyruvate dehydrogenase complex (PDHC) in cultured cells or other tissues from patients with Leigh's disease (subacute necrotizing encephalomyelopathy). We therefore undertook studies to elucidate the molecular basis of the defect of PDHC in cultured skin fibroblasts from two patients with Leigh's disease. The deficit of total PDHC activity in homogenates of Leigh's disease fibroblasts could be restored by adding exogenous lipoamide dehydrogenase (LAD, E3), the third component of PDHC. The LAD in these Leigh's disease cells had a markedly reduced ability (less than 20% of normal LAD) to reconstitute with other PDHC components to form active enzyme complex. A polyclonal antibody to pig heart LAD inhibited LAD activity in control cells more efficiently than in Leigh's disease cells. Other mitochondrial enzyme activities and growth of these two Leigh's disease cells appeared normal. These results suggest that the deficiency of PDHC in these two patients with Leigh's disease was due to a structural abnormality of the LAD component of PDHC.
几个研究小组报告了患有 Leigh 病（亚急性坏死性脑脊髓病）患者的培养细胞或其他组织中丙酮酸脱氢酶复合体（PDHC）的异常情况。因此，我们开展了研究，以阐明两名 Leigh 病患者培养的皮肤成纤维细胞中 PDHC 缺陷的分子基础。通过添加外源性硫辛酰胺脱氢酶（LAD，E3），即 PDHC 的第三个组分，可恢复 Leigh 病成纤维细胞匀浆中总 PDHC 活性的不足。这些 Leigh 病细胞中的 LAD 与其他 PDHC 组分重构以形成活性酶复合体的能力明显降低（不到正常 LAD 的 20%）。针对猪心 LAD 的多克隆抗体对对照细胞中 LAD 活性的抑制作用比对 Leigh 病细胞更有效。这两个 Leigh 病细胞的其他线粒体酶活性和生长情况似乎正常。这些结果表明，这两名 Leigh 病患者中 PDHC 的缺乏是由于 PDHC 的 LAD 组分存在结构异常。
