IRON AND TOXICITES AND PATHOLOGIES

这是一个建议，继续研究铁在各种疾病中的作用。 毒性和病理学。 铁非常活泼，能够氧化 生物分子直接或间接通过羟基的产生 通过芬顿反应（Fe + H2 O2产生Fe 111 + OH + OH-）， 铁可以从铁储存蛋白铁蛋白中释放出来， 各种毒素的自由基形式，由NADPH-细胞色素还原酶产生， 和超氧化物，这可能是由氧化还原循环的毒素产生的。 免费 化学物质的单电子氧化也能产生自由基 通过过氧化物酶。 我们认为这些酶（过氧化物酶）和各种 其他化学物质也可以从铁蛋白中释放铁。 我们最近 发现O2也是通过H2 O2被各种氧化剂氧化而产生的。 过氧化物酶产生的自由基。 因此，我们建议调查 通过过氧化物酶和毒素从铁蛋白中释放铁， 是过氧化物酶的底物（即，对苯二酚类，氯丙嗪， 苯妥英，二甲双酮和三甲双酮，氨基三唑，四甲基联苯胺， 等）。 我们还将研究O2在铁释放中的作用 从铁蛋白中分离出来 另一方面，铁蛋白 可能是保护免受铁的毒性作用，如果有一个 将铁放入铁蛋白的有效机制。 我们不相信 铁蛋白具有自身的铁负载能力。 我们认为，这是 铜蓝蛋白的作用。然而，我们必须证明铜蓝蛋白是一种 组织酶，并且它与铁蛋白结合以有效地装载 铁进入铁蛋白。 我们还将证明，铜蓝蛋白和 铁蛋白对铁催化的脂质过氧化有保护作用， 上述的释放机制，特别是在各种 能与铁络合的生物分子。 我们还建议确定， 几种建议的抗氧化剂可以螯合铁， 和铁蛋白依赖性脂质过氧化作用。

This is a proposal to continue our research on the role of iron in various toxicities and pathologies. Iron is very reactive, able to oxidize biomolecules directly or indirectly by the generation of the hydroxyl radical (OH) by Fenton reaction (Fe + H202 yielding Fe111 + 0H + OH-). Iron can be released from the iron storage protein ferritin by the free radical form of various toxins, generated by NADPH-cytochrome reductase, and superoxide, which can result from toxins that redox cycle. Free radicals can also be produced by the one-electron oxidation of chemicals by peroxidases. We propose that these enzymes (peroxidases) and various other chemicals can also release iron from ferritin. We have recently discovered that 02 is also produced by the oxidation of H202 by various radicals produced by peroxidases. We therefore propose to investigate the release of iron from ferritin by peroxidases and toxins that are known to be substrates for peroxidases (i.e., hydroquinones, chlorpromazine, phenytoin, di- and trimethadione, aminotriazole, tetramethylbenzidine, etc.). We will also investigate the role of O2 in the release of iron from ferritin by these chemicals and enzymes. On the other hand, ferritin may be protective against the toxic effects of iron if there is an efficient mechanism for placing the iron into ferritin. We don't believe that ferritin has its own iron loading ability. We propose that this is the role of ceruloplasmin. However, we must show that ceruloplasmin is a tissue enzyme and that it associates with ferritin to efficiently load iron into the ferritin. We will also demonstrate that ceruloplasmin and ferritin are protective against iron-catalyzed lipid peroxidation by the release mechanisms noted above, especially in the presence of various biomolecules that can complex with iron. We also propose to determine if several proposed antioxidants that may chelate iron can inhibit peroxidase and ferritin-dependent lipid peroxidation.