The Relationship of Diphenyleneiodonium-Induced Hypoglycaemia to the Specific Covalent Modification of NADH-Ubiquinone Oxidoreductase
The Relationship of Diphenyleneiodonium-Induced Hypoglycaemia to the Specific Covalent Modification of NADH-Ubiquinone Oxidoreductase
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DOI：
10.1042/bst0070103
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发表时间：
1979-02-01
影响因子：
3.9
通讯作者：
Bloxham, David P.
中科院分区：
文献类型：
--
作者：
Bloxham, David P.
关于二苯四碘降糖作用的第一篇报道可以追溯到Stewart和Hanley（1969）的观察，他们表明二苯四酮是已知的最有效的降糖化合物之一。在一些动物物种中，该化合物仅以4毫克/公斤的剂量就可引起不可逆的低血糖，导致死亡。有趣的是，关于二苯二酮的第一份报告明确地侧重于其行动的两个主要特点，这将在本文中加以阐述。首先，该化合物具有较强的代谢氧化抑制作用；其次，该抑制作用具有不可逆的特点。随后，Holland & Sherratt（1972）对线粒体氧化的抑制进行了研究，他们发现二苯乙烯（5-10b~）完全抑制了离体大鼠肝脏线粒体中adp -二硝基酚刺激的琥珀酸盐氧化。这种抑制被发现是C1依赖的，因为黄素连接底物的抑制在无cy的培养基中不发生。二苯二酮被发现能催化线粒体膜上的CI-/ oh -交换
The first report on the hypoglycaemic action of diphenyleneiodonium dates to observations by Stewart & Hanley (1969), who showed that it was one of the most potent hypoglycaemic compounds known. In several animal species the compound caused irreversible hypoglycaemia resulting in death at a dose of only 4mg/kg. Interestingly, the very first report on diphenyleneiodonium clearly focused on the two main features of its actions which will be developed in this article. Firstly the compound was a strong inhibitor of metabolic oxidation and secondly the inhibition showed irreversible characteristics.The inhibition of mitochondrial oxidation was subsequently pursued by Holland & Sherratt (1972), who showed that diphenyleneiodonium (5-10b~) completely inhibited ADP-linked dinitrophenol-stimulated oxidation of succinate by isolated rat liver mitochondria. This inhibition was found to be C1--dependent, since inhibition of flavin-linked substrates did not occur in CY-free media. Diphenyleneiodonium was found to catalyse a CI-/OH-exchange across the mitochondrial membrane, and this