PORPHYRIN ION RADICAL METABOLITES AND THEIR REACTIONS

卟啉离子自由基代谢物及其反应

• 批准号: 3918694
• 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/3918694
• 关键词: NADPH cytochrome c2 reductase; anions; biophysics; cations; congenital erythropoietic porphyria; cytochrome P450; electron spin resonance spectroscopy; electron transport; free radicals; microsomes; molecular biology; oxygen consumption; porphyrin metabolism; porphyrins; 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 1 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.

泌尿磷脂I，积聚在先天性的身体组织中 红细胞生物斑岩患者可以接受酶促的一 当合适的 存在还原辅因子。 我们已经证明了厌氧 含有NADPH和泌尿磷脂1的微粒体孵育1 卟啉阴离子自由基的电子自旋共振光谱。 抑制剂研究表明NADPH-CYTOCHROME P-450还原酶 是电子供体。 这个激进的经历了二阶衰变 由于自由基的非酶造成比例。 有氧运动 还研究了微粒体孵育以减少 通过监测氧气消耗和自旋 - 诱捕超氧化物。 这些实验表明 电子从卟啉自由基到分子氧的转移 确实发生了，但由于自由基阴离子的形成缓慢，否 可以检测到高于基础水平的氧气 微粒体孵育。 泌尿照蛋白I的光摄取 还研究了有氧和厌氧孵育。 相似的 通过光激活的光蛋白II获得了结果 抗肿瘤剂。 多种卟啉的氧化 也已经研究了过氧化物酶的阳离子自由基。 由于辣根过氧化物酶的中间酶，化合物 我本身就是卟啉IX阳离子激进，这项工作将有 对电子转移以及卟啉代谢的影响。