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On Novel Features of the Proton Leak and Possibility of Uncoupling Population of Mitochondria in Brown Adipose Tissue

机译:棕色脂肪组织中质子泄漏的新特征和线粒体解偶联的可能性

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In many studies on succinate as a substrate, the respiration of brown adipose tissue mitochondria is partially uncoupled that is associated with proton leak. NAD-dependent substrates (pyruvate + malate) were also used in a number of works. Oxidation of NAD-dependent substrates occurs with greater coupling where the respiration rate is higher and state 4 (resting state of mitochondrial respiration) lower than that with succinate. It is suggested that the oxidation of these substrates occurs in different ways. Further, a series of studies with a large number of oxidation substrates (NAD-dependent substrates, succinate, NADH and ascorbate + cytochrome c) was performed. It was found that NADH and ascorbate oxidized in BAT mitochondria very intensive and completely uncoupled with ATP synthesis. To explain these data, it is necessary to carry in certain changes in the existing proton leak scheme. In BAT mitochondria, it was also found high activity of Mg~(2+)-stimulated ATPase, sensitive to olygomycin. It has also high activity than DNP-stimulated ATPase. To explain of oxidation of many substrates on uncoupling way and existence of Mg~(2+)-stimulated ATPase in BAT mitochondria the review suggests an alternative concept, according to which two mitochondrial subpopulations are present in the suspension of BAT mitochondria. One of them carries out synthesis of ATP as generally accepted, and the second one – with a highly porous membrane, oxidizes exogenous NADH (GDP sensitive), ascorbate (+cytochrome c) and other substrates uncoupled way. Apparently, a special population of mitochondria can exist in brown fat that can oxidize many substrates in uncoupling way for thermogenesis.
机译:在许多以琥珀酸酯为底物的研究中,棕色脂肪组织线粒体的呼吸部分解耦,这与质子泄漏有关。 NAD依赖的底物(丙酮酸+苹果酸)也被用于许多研究中。与琥珀酸相比,NAD依赖性底物的氧化具有更大的偶联作用,其中呼吸速率更高,状态4(线粒体呼吸的静止状态)更低。建议这些底物的氧化以不同的方式发生。此外,对大量氧化底物(NAD依赖性底物,琥珀酸盐,NADH和抗坏血酸盐+细胞色素c)进行了一系列研究。已发现,NADH和抗坏血酸盐在BAT线粒体中被强烈氧化,并且与ATP合成完全不相关。为了解释这些数据,有必要对现有的质子泄漏方案进行某些更改。在BAT线粒体中,还发现了对Mg〜(2+)刺激的ATP酶具有高活性,对奥林霉素敏感。它也比DNP刺激的ATPase具有更高的活性。为了解释以解偶联方式氧化许多底物的氧化以及BAT线粒体中Mg〜(2+)刺激的ATPase的存在,本综述提出了一个替代概念,即在BAT线粒体的悬浮液中存在两个线粒体亚群。其中一种进行公认的ATP合成,第二种-具有高度多孔的膜,以脱偶联的方式氧化外源NADH(对GDP敏感),抗坏血酸盐(+细胞色素c)和其他底物。显然,特殊的线粒体可能存在于棕色脂肪中,该脂肪可以以解偶联的方式氧化许多底物以促进生热。

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