PORPHYRIN ION RADICAL METABOLITES AND THEIR REACTIONS

卟啉离子自由基代谢物及其反应

• 批准号: 3855919
• 负责人: R P MASON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3855919
• 关键词: NADPH cytochrome c2 reductase; anions; antineoplastics; biophysics; congenital erythropoietic porphyria; cytochrome P450; electron spin resonance spectroscopy; electron transport; free radicals; microsomes; oxidoreductase inhibitor; oxygen consumption; photochemistry; porphyrin metabolism; porphyrins; reduction; superoxides

Uroporphyrin I, which accumulates in body tissues of congenital erythropoietic porphyria patients, can undergo an enzymatic one-electron reduction to the porphyrin anion radical when a suitable reducing cofactor is present. We have demonstrated that anaerobic microsomal incubations containing NADPH and uroporphyrin I give an electron spin resonance spectrum of a porphyrin anion free radical. Inhibitor studies indicate that NADPH-cytochrome P-450 reductase is the electron donor. This radical undergoes a second-order decay due to nonenzymatic disproportionation of the radical. Aerobic microsomal incubations were also investigated for the reduction of oxygen to superoxide by monitoring oxygen consumption and the spin-trapping of superoxide. These experiments demonstrated that electron transfer from the porphyrin radical to molecular oxygen does occur, but due to the slow formation of the radical anion. No oxygen consumption above the basal level could be detected in the microsomal incubations. The photoreduction of uroporphyrin I in aerobic and anaerobic incubations was also investigated. Similar results have been obtained with photofrin II, a photo-activated antitumor agent. The oxidation of a variety of porphyrins to cation free radicals by peroxidases also has been investigated. Since the enzyme intermediate of horseradish peroxidase, compound I, is itself a porphyrin IX cation radical, this work will have implications for electron transfer as well as porphyrin metabolism.

尿卟啉I，它积累在先天性 红细胞生成性卟啉病患者，可以进行酶促单电子 当合适的还原辅因子 存在。 我们已经证明厌氧微粒体孵育 含有NADPH和尿卟啉I的电子自旋共振 卟啉阴离子自由基光谱。 抑制剂研究表明 NADPH-细胞色素P-450还原酶是电子供体。 这种激进 由于非酶促分解， 激进分子 还对需氧微粒体孵育进行了研究， 通过监测氧消耗量将氧还原为超氧化物， 超氧化物的自旋捕获。 这些实验表明，电子 从卟啉自由基到分子氧的转移确实发生，但由于 自由基阴离子的缓慢形成。 没有氧气消耗超过 在微粒体孵育物中可检测到基础水平。 的 尿卟啉I在有氧和厌氧培养中的光还原是 也调查了。 用Photofrin II获得了类似的结果， 一种光活化抗肿瘤剂。 各种各样的氧化物 卟啉通过过氧化物酶对阳离子自由基的作用也已被 研究了 由于辣根过氧化物酶的酶中间体， 化合物I，本身是卟啉IX阳离子自由基，这项工作将有 电子转移以及卟啉代谢的影响。