Comparative biochemical studies in fibroblasts from patients with different forms of Leigh syndrome.
Comparative biochemical studies in fibroblasts from patients with different forms of Leigh syndrome.
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不同形式 Leigh 综合征患者成纤维细胞的比较生化研究。
DOI：
10.1007/bf01799347
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发表时间：
1996
影响因子：
4.2
通讯作者：
DiMauro,S
中科院分区：
文献类型：
--
作者：
Vazquez-Memije,ME;Shanske,S;Santorelli,FM;Kranz-Eble,P;Davidson,E;DeVivo,DC;DiMauro,S
我们比较了 Leigh 综合征 (LS) 患者培养的成纤维细胞线粒体中的呼吸链酶活性、ATP 合成和 ATP 水解，原因是：(i) 细胞色素氧化酶 (COX) 缺乏 (#6)； (ii) 丙酮酸脱氢酶复合物 (PDHC) 缺乏症 (#4)； (iii) mtDNA 的 ATPase 6 基因中存在 T8993G 突变的母系遗传 LS (MILS) (#5)。 MILS 患者的酶活性正常，而 COX 和 PDHC 缺乏的患者酶活性不同程度下降。所有三组中 ATP 水解均正常或轻度下降。相比之下，所有患者的 ATP 合成均减少，但 MILS 患者的 ATP 合成减少更为明显，尤其是以丙酮酸/苹果酸为底物时。这些研究表明，ATP 生成受损是所有三种类型 LS 的共同特征，但 MILS 中的情况更为严重且更具特异性，这与遗传缺陷一致。
We have compared respiratory chain enzyme activities, ATP synthesis, and ATP hydrolysis in cultured fibroblast mitochondria from patients with Leigh syndrome (LS) due to: (i) cytochrome oxidase (COX) deficiency (#6); (ii) pyruvate dehydrogenase complex (PDHC) deficiency (#4); and (iii) maternally inherited LS (MILS) with the T8993G mutation in the ATPase 6 gene of mtDNA (#5). Enzyme activities were normal in patients with MILS and variably decreased in those with COX and PDHC deficiency. ATP hydrolysis was normal or mildly decreased in all three groups. In contrast, ATP synthesis was decreased in all patients but more markedly in those with MILS, and especially with pyruvate/malate as substrate. These studies show that impaired ATP production is the common feature of all three forms of LS, but it is both more severe and more specific in MILS, consistent with the genetic defect.