Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency.
Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency.
复制标题
3-酮硫解酶缺陷男孩培养的成纤维细胞中线粒体乙酰乙酰辅酶 A 硫解酶生物合成存在缺陷。
DOI：
10.1172/jci113388
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
T. Hashimoto
中科院分区：
文献类型：
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作者：
S. Yamaguchi;Tadao OMi;N. Sakura;S. Miyazawa;T. Hashimoto
3-酮硫解酶缺乏症的病因已被归因于线粒体乙酰乙酰-CoA硫解酶的缺陷，因为相关材料中的乙酰乙酰-CoA硫解酶活性不被K+激活，这是该酶的特性。我们研究了酶蛋白和线粒体乙酰乙酰辅酶A硫解酶的生物合成，使用培养的皮肤成纤维细胞从一个5岁的男孩与3-酮硫解酶缺乏症。获得了以下结果。(a)K+对乙酰乙酰-CoA硫解酶活性的活化为零;（B）酶活性不受线粒体乙酰乙酰-CoA硫解酶抗体处理的影响;（c）在免疫印迹分析中未检测到线粒体乙酰-CoA硫解酶蛋白的信号;（d）使用[35 S]甲硫氨酸的皮肤成纤维细胞脉冲追踪实验显示，该酶中未掺入放射性。因此，该患者的成纤维细胞由于其生物合成缺陷而缺乏线粒体乙酰乙酰辅酶A硫解酶蛋白。
The etiology of 3-ketothiolase deficiency has been attributed to a defect of mitochondrial acetoacetyl-CoA thiolase because the acetoacetyl-CoA thiolase activity in related materials is not activated by K+, a property characteristic for this enzyme. We studied the enzyme protein and the biosynthesis of mitochondrial acetoacetyl-CoA thiolase, using cultured skin fibroblasts from a 5-yr-old boy with 3-ketothiolase deficiency. The following results were obtained. (a) Activation of acetoacetyl-CoA thiolase activity by K+ was nil; (b) The enzyme activity was not affected by treatment with the antibody against mitochondrial acetoacetyl-CoA thiolase; (c) A signal for mitochondrial acetoacetyl-CoA thiolase protein was not detected in the immunoblot analysis; and (d) Pulse-chase experiments of skin fibroblasts, using [35S]methionine, revealed no incorporation of radioactivity into this enzyme. Therefore, fibroblasts from this patient lacked mitochondrial acetoacetyl-CoA thiolase protein due to a defect in its biosynthesis.