Decreased activities of ubiquinol:ferricytochrome c oxidoreductase (complex III) and ferrocytochrome c:oxygen oxidoreductase (complex IV) in liver mitochondria from rats with hydroxycobalamin[c-lactam]-induced methylmalonic aciduria.
Decreased activities of ubiquinol:ferricytochrome c oxidoreductase (complex III) and ferrocytochrome c:oxygen oxidoreductase (complex IV) in liver mitochondria from rats with hydroxycobalamin[c-lactam]-induced methylmalonic aciduria.
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DOI：
10.1016/s0021-9258(18)54810-9
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发表时间：
1991-11
期刊：
影响因子：
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通讯作者：
S. Krahenbuhl;Mei Chang;Eric P. Brass;Charles L. Hoppel
中科院分区：
文献类型：
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作者：
S. Krahenbuhl;Mei Chang;Eric P. Brass;Charles L. Hoppel
羟钴胺[c-内酰胺]（HCCL）是一种诱导甲基丙二酸尿的钴胺类似物，用HCCL治疗的大鼠肝脏线粒体含量增加，每个肝细胞的丙酮酸和棕榈酸的氧化代谢增加。本研究旨在描述HCCL处理大鼠分离肝脏线粒体的氧化代谢特征。5-6周后，hccl处理大鼠线粒体中各种底物的状态3氧化速率降低。二硝基酚解偶联线粒体获得了类似的线粒体氧化率降低，排除了作为观察到的线粒体氧化减少的原因的有缺陷的磷酸化。hccl处理大鼠线粒体氧化酶活性降低，复合物IV出现缺陷。对呼吸链复合物的研究显示，与对照组相比，5-6周hccl处理大鼠线粒体中泛醇：铁细胞色素c氧化还原酶（复合物III）活性降低32%，铁细胞色素c：氧氧化还原酶（复合物IV）活性降低72%。hccl处理大鼠肝脏线粒体每mg线粒体蛋白的细胞色素含量也降低（与对照大鼠相比，细胞色素b降低25%，细胞色素a + a3降低52%）。hccl处理的大鼠是研究肝线粒体呼吸链缺陷后果的动物模型。
Rats treated with hydroxycobalamin[c-lactam] (HCCL), a cobalamin analogue that induces methylmalonic aciduria, have increased hepatic mitochondrial content and increased oxidative metabolism of pyruvate and palmitate per hepatocyte. The present studies were undertaken to characterize oxidative metabolism in isolated liver mitochondria from rats treated with HCCL. After 5-6 weeks, state 3 oxidation rates for diverse substrates are reduced in mitochondria from HCCL-treated rats. Similar reductions of mitochondrial oxidation rates are obtained with dinitrophenol-uncoupled mitochondria excluding defective phosphorylation as a cause for the observed decrease in mitochondrial oxidation. The activities of mitochondrial oxidases are reduced in HCCL-treated rats and demonstrate a defect in complex IV. Investigation of the complexes of the respiratory chain reveals a 32% decrease of ubiquinol:ferricytochrome c oxidoreductase (complex III) activity and a 72% decrease of ferrocytochrome c:oxygen oxidoreductase (complex IV) activity in mitochondria from 5-6-week HCCL-treated rats as compared with controls. Liver mitochondria from HCCL-treated rats also demonstrate decreased cytochrome content per mg of mitochondrial protein (25% decrease of cytochrome b and 52% decrease of cytochrome a + a3 as compared with control rats). The HCCL-treated rat represents an animal model for the study of the consequences of respiratory chain defects in liver mitochondria.