Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.
J Bioenerg Biomembr. 2011 Feb;43(1):39-46. doi: 10.1007/s10863-011-9330-2.
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.
甲基丙二酸血症是最常见的遗传性代谢紊乱之一，涉及神经功能缺损。体外实验、动物模型研究和人类患者的组织分析表明，这种疾病中线粒体能量代谢广泛受损。本综述总结了甲基丙二酸血症中发生的线粒体能量代谢变化，主要关注堆积的甲基丙二酸的影响，并概述了不同实验模型中的发现结果。总的来说，迄今为止的实验表明，这种疾病中线粒体的损伤是通过抑制特定的酶和转运蛋白、限制线粒体代谢途径底物的可用性以及氧化损伤的组合作用发生的。
