Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human
Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human
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DOI：
10.1016/s0925-4439(97)00035-5
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发表时间：
1997-08-22
影响因子：
6.2
通讯作者：
Rotig, A
中科院分区：
文献类型：
--
作者：
Rustin, P;Bourgeron, T;Rotig, A
克雷布斯循环障碍是一组罕见的人类疾病，考虑到我们目前对克雷布斯循环功能和生物发生的了解，这种疾病呈现出惊人的复杂性。作为细胞新陈代谢的转盘，它普遍存在于生物体及其酶组分中，被认为是典型的看家基因编码的。然而，对由于所考虑的基因的有害突变而出现特定的Krebs循环酶缺陷的患者的调查，导致通过揭示器官特异性损伤来重新考虑这一简单的设想，主要影响神经肌肉系统。这通常会忽略代谢也强烈依赖线粒体能量代谢的器官，如心脏、肾脏或肝脏。此外，在一些患者中，还观察到组织特异性酶缺陷的复杂模式。缺乏Krebs周期基因的功能额外拷贝表明，这种复杂的表达模式应归因于组织特有的转录和/或翻译活动调节，以及细胞对Krebs周期功能缺陷的可变适应性。(C)1997年爱思唯尔科学公司。
Krebs cycle disorders constitute a group of rare human diseases which present an amazing complexity considering our current knowledge on the Krebs cycle function and biogenesis. Acting as a turntable of cell metabolism, it is ubiquitously distributed in the organism and its enzyme components encoded by supposedly typical house-keeping genes. However, the investigation of patients presenting specific defects of Krebs cycle enzymes, resulting from deleterious mutations of the considered genes, leads to reconsider this simple envision by revealing organ-specific impairments, mostly affecting neuromuscular system. This often leaves aside organs the metabolism of which strongly depends on mitochondrial energy metabolism as well, such as heart, kidney or liver. Additionally, in some patients, a complex pattern of tissue-specific enzyme defect was also observed. The lack of functional additional copies of Krebs cycle genes suggests that the complex expression pattern should be ascribed to tissue-specific regulations of transcriptional and/or translational activities, together with a variable cell adaptability to Krebs cycle functional defects. (C) 1997 Elsevier Science B.V.