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.

尿卟啉I，它积累在先天性 红细胞生成性卟啉病患者，可以经历酶促反应- 电子还原为卟啉阴离子自由基时， 还原辅因子存在。 我们已经证明厌氧 含有NADPH和尿卟啉1的微粒体孵育给出了 卟啉阴离子自由基的电子自旋共振谱。 抑制剂研究表明，NADPH-细胞色素P-450还原酶 是电子供体。 这个自由基经历二级衰变 由于自由基的非酶促分解。 有氧 还研究了微粒体孵育以减少 通过监测氧气消耗和自旋， 超氧化物的捕获。 这些实验证明 电子从卟啉自由基转移到分子氧 但由于自由基阴离子的缓慢形成， 氧消耗高于基础水平可以检测到在 微粒体孵育。 尿卟啉Ⅰ在水溶液中的光还原 还研究了需氧和厌氧培养。 类似 结果已经用Photofrin II，一种光活化的 抗肿瘤剂。 各种卟啉氧化成 还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酶中间体，化合物 I，本身是卟啉IX阳离子自由基，本工作将有 电子转移以及卟啉代谢的影响。