Kerr D S, Ho L, Berlin C M, Lanoue K F, Towfighi J, Hoppel C L, Lusk M M, Gondek C M, Patel M S
Department of Pediatrics, Rainbow Babies and Childrens Hospital, Cleveland, OH 44106.
Pediatr Res. 1987 Sep;22(3):312-8. doi: 10.1203/00006450-198709000-00015.
An infant with lactic acidosis and developmental delay had neuropathological changes consistent with Leigh's necrotizing encephalomyelopathy. Total pyruvate dehydrogenase complex (PDC) activity was low relative to controls in lymphocytes (0.2 versus 1.9 +/- 0.6 SD nmol/min/mg protein) and cultured skin fibroblasts (0.9 versus 2.7 +/- 1.0). Liver, muscle, heart, and kidney mitochondria oxidized several substrates normally, but did not oxidize pyruvate. PDC activity was absent in these mitochondria (0.1 versus 9.8 +/- 4.2 in liver and 0.7 versus 75 +/- 26 in muscle) and was very low in all tissue homogenates. Activity of the first component was low in liver mitochondria, whereas activities of the second and third components were normal. Western blot analysis of tissue proteins showed normal amounts of second and third component of PDC but undetectable to trace amounts of both alpha and beta subunits of the first component of PDC in liver, brain, kidney, heart, and skin fibroblasts. Thus, profound systemic deficiency of PDC was due to lack of both subunit proteins of the first component of PDC.
一名患有乳酸性酸中毒和发育迟缓的婴儿出现了与 Leigh 坏死性脑脊髓病一致的神经病理学变化。与对照组相比，淋巴细胞中的总丙酮酸脱氢酶复合物（PDC）活性较低（0.2 对 1.9±0.6 SD nmol/分钟/毫克蛋白质），培养的皮肤成纤维细胞中也是如此（0.9 对 2.7±1.0）。肝脏、肌肉、心脏和肾脏线粒体通常能氧化几种底物，但不能氧化丙酮酸。这些线粒体中不存在 PDC 活性（肝脏中为 0.1 对 9.8±4.2，肌肉中为 0.7 对 75±26），并且在所有组织匀浆中都非常低。肝脏线粒体中第一成分的活性较低，而第二和第三成分的活性正常。对组织蛋白进行的蛋白质印迹分析显示，PDC 的第二和第三成分含量正常，但在肝脏、大脑、肾脏、心脏和皮肤成纤维细胞中，PDC 第一成分的α和β亚基含量均无法检测到或仅为微量。因此，PDC 的严重全身性缺乏是由于 PDC 第一成分的两个亚基蛋白均缺乏所致。
