ROLE OF IRON IN TOXICITIES AND PATHOLOGIES

这项建议是为了继续研究我们提出的涉及铁的建议 在某些毒性和病理性方面。我们已经提议，铁 储存蛋白铁蛋白可能是这种铁的来源。超氧化物，以及 尤其是有机自由基，从铁蛋白中释放铁。这铁一般的意志 催化组织的氧化，包括脂质过氧化。我们建议 这可能是化学物质氧化还原循环的一种机制 有毒的。我们还提出，铁蛋白可能是一种保护性蛋白质，因为 将铁放入铁蛋白的有效方法。我们建议 铜蓝蛋白可以做到这一点，因为它是一种有效的铁氧合酶，它 不释放部分还原的氧物种，如氢 过氧化氢。因此，铁蛋白和铜蓝蛋白的组合可能具有 抗氧化活性。越来越多的证据表明铜蓝蛋白是一种 重要的细胞内酶和肝外酶。我们建议进一步 研究这一假设。我们还将对这项提议进行调查 铁蛋白和铜蓝蛋白可能都是由氧化还原循环诱导的 毒素。我们还必须进一步调查铁蛋白，因为我们发现 它对百草枯和阿霉素释放铁的敏感性不同。 这取决于它被分离出来的组织。我们正在提议 检验这一假设，即这是由于重和轻含量不同所致 多肽链。我们还建议检验这样的假设，即某些复杂的 可能存在于铁蛋白和铜蓝蛋白之间。最后，我们建议 将我们的研究扩展到研究已被提议具有 “氧化酶”活性。我们先从谷氨酰酶说起 转肽酶。我们认为，酶的原样产物 通常检测的是良好的铁还原剂和随后的氧化 这种铁是与此相关的“氧化酶”活性的来源。 酵素。这种铁在生理条件下通常控制得很好。 因此，γ-谷氨酰转肽酶的“氧化酶”活性很可能不是 具有生理意义的，除非在不寻常的情况下。

This proposal is to continue research on our proposal that iron is involved in certain toxicities and pathologies. We have proposed that the iron storage protein ferritin may be the source of this iron. Superoxide, and especially organic radicals, release iron from ferritin. This iron will catalyze the oxidation of tissues including lipid peroxidation. We propose that this may be a mechanism by which chemicals that redox cycle may be toxic. We also propose that ferritin may be a protective protein given an efficient method to place the iron into ferritin. We propose that ceruloplasmin may accomplish this as it is an effective ferroxidase which does not release partially reduced species of oxygen such as hydrogen peroxide. Thus, a combination of ferritin and ceruloplasmin may have antioxidant activity. Evidence is mounting that ceruloplasmin is an important intracellular, extrahepatic enzyme. We propose to further investigate this hypothesis. We are also going to investigate the proposal that both ferritin and ceruloplasmin may be induced by redox cycling toxins. We also have to further investigate ferritin as we have found that it differs in susceptibility to iron release by paraquat and adriamycin depending upon the tissue from which it was isolated. We are proposing to test the hypothesis that this is due to different content of heavy vs light peptide chains. We also propose to test the hypothesis that some complex may exist between ferritin and ceruloplasmin. Finally, we propose to extend our research to investigate enzymes that have been proposed to have "oxidase" activity. We will start with the enzyme gamma-glutamyl transpeptidase. We propose that the products of the enzyme as it is usually assayed are good iron reductants and that subsequent oxidation of this iron is the source of the "oxidase" activity associated with this enzyme. This iron is usually well controlled in physiological conditions so the "oxidase" activity of gamma-glutamyl transpeptidase is probably not of physiological significance except in unusual situations.