Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia
Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia
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DOI：
10.1007/s10863-011-9330-2
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发表时间：
2011-02-01
影响因子：
3
通讯作者：
Castilho, Roger F.
中科院分区：
文献类型：
--
作者：
Melo, Daniela R.;Kowaltowski, Alicia J.;Castilho, Roger F.
甲基丙二酸血症是一种最常见的涉及神经功能缺陷的遗传性代谢疾病。体外实验、动物模型研究和来自人类患者的组织分析表明，这种疾病存在线粒体能量代谢的广泛损害。本文综述了甲基丙二酸血症中线粒体能量代谢的变化，重点介绍了甲基丙二酸积累对线粒体能量代谢的影响，并概述了不同实验模型的结果。总的来说，迄今为止的实验表明，这种疾病的线粒体损伤是通过抑制特定酶和转运体、限制线粒体代谢途径底物的可用性和氧化损伤的组合发生的。
Methylmalonic acidemia is one of the most prevalent inherited metabolic disorders involving neurological deficits. In vitro experiments, animal model studies and tissue analyses from human patients suggest extensive impairment of mitochondrial energy metabolism in this disease. This review summarizes changes in mitochondrial energy metabolism occurring in methylmalonic acidemia, focusing mainly on the effects of accumulated methylmalonic acid, and gives an overview of the results found in different experimental models. Overall, experiments to date suggest that mitochondrial impairment in this disease occurs through a combination of the inhibition of specific enzymes and transporters, limitation in the availability of substrates for mitochondrial metabolic pathways and oxidative damage.