PORPHYRIN ION RADICAL METABOLITES AND THEIR REACTIONS

尿卟啉I在先天性心脏病患者体内组织中的蓄积 红细胞生成性卟啉症患者，可经历酶促单电子 当合适的还原辅因子时，还原为卟啉阴离子自由基 是存在的。我们已经证明了厌氧微粒体孵化 含NADPH和尿卟啉I的电子自旋共振 一种卟啉阴离子自由基的光谱。抑制剂研究表明 NADPH-细胞色素P-450还原酶是电子供体。这个激进分子 由于非酶歧化引起的二级衰变 激进分子。有氧微体孵化也被研究为 通过监测耗氧量和温度，将氧气还原为超氧化物 超氧化物的自旋捕获。这些实验证明，电子 确实发生了从卟啉自由基到分子氧的转移，但由于 与自由基阴离子的缓慢形成有关。以上无耗氧量 在微粒体孵育过程中可检测到基础水平。这个 研究了好氧和厌氧培养条件下尿卟啉I的光还原反应. 也进行了调查。PHOTOFRIN II也得到了类似的结果， 一种光激活的抗肿瘤药物。不同种类的氧化剂 卟啉通过过氧化物酶对阳离子自由基的作用也已被研究 调查过了。由于辣根过氧化物酶的酶中间体， 化合物I，本身就是一种卟啉IX阳离子自由基，这项工作将有 对电子转移和卟啉代谢的影响。

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.