Sentjurc M, Pecar S, Chen K, Wu M, Swartz H
University of Illinois, College of Medicine, Urbana-Champaign, IL.
Biochim Biophys Acta. 1991 Mar 4;1073(2):329-35. doi: 10.1016/0304-4165(91)90139-8.
Previous data from model systems indicated that the proxyl nitroxides should be especially resistant to bioreduction and therefore could be an effective solution to this often problematic characteristic of nitroxides. Therefore, we investigated the rate of reduction by cells and by the usual model system, ascorbate, of four proxyl nitroxides and three reference nitroxides. We found that, while the rate of reduction by ascorbate of the proxyl nitroxides was slower than the rate of a prototypic pyrrolidine nitroxide (PCA), the reverse was true for reduction by cells. We also studied the rate of oxidation of the corresponding hydroxylamines. The rate of oxidation by cells of the proxyl hydroxylamines was relatively fast, especially for the most lipophilic derivative. These results indicate that: (i) proxyl nitroxides may not be unusually resistant to bioreduction by functional biological systems; (ii) accurate knowledge of relative rates of metabolism of nitroxides and hydroxylamines in cells and tissues will require direct studies in these systems because the rates may not closely parallel those observed in model (chemical) systems; and (iii) proxyl nitroxides show potential value as agents to measure oxygen concentrations by the rates of oxidation of their corresponding hydroxylamines.
来自模型系统的先前数据表明，亚硝基氧自由基应该特别抗生物还原，因此可能是解决亚硝基氧化物这一常见问题特性的有效方法。因此，我们研究了四种亚硝基氧自由基和三种参比亚硝基氧化物被细胞以及常用模型系统抗坏血酸还原的速率。我们发现，虽然抗坏血酸对亚硝基氧自由基的还原速率比原型吡咯烷亚硝基氧化物（PCA）的还原速率慢，但细胞还原的情况则相反。我们还研究了相应羟胺的氧化速率。亚硝基羟胺的细胞氧化速率相对较快，尤其是对于亲脂性最强的衍生物。这些结果表明：（i）亚硝基氧自由基可能对功能性生物系统的生物还原没有特别的抗性；（ii）准确了解细胞和组织中亚硝基氧化物和羟胺的相对代谢速率将需要在这些系统中进行直接研究，因为这些速率可能与模型（化学）系统中观察到的速率不太一致；（iii）亚硝基氧自由基作为通过其相应羟胺的氧化速率来测量氧浓度的试剂具有潜在价值。
