Investigation of the intermediary steps and electron transfer mechanism of heme degradation by heme oxygenase

点击翻译按钮获取中文摘要

Heme oxygenase(HO) catalyzes the heme degradation utilizing molecular oxygen and reducing equivalents from NADPH-cytochrome P450 reductase(CPR). The purposes of this study are the characterization of electron pathway between NAPDH bound to CPR to heme bound to HO. To probe the cleavage mechanism of oxaporphyrin ring of ferrousα-verdoheme, an intermediate in the HO reaction, ferrous verdoheme-rat HO-1 complex was prepared under anaerobic conditions. Electrochemical reduction of the complex was performed under anaerobic conditions and the reduction potential for one-electron reduction of the oxaporphyrin ring of ferrous verdoheme was determined. Effects of ligands such as CO on the electrochemical reduction and the electron transfer from NADPH-cytochrome P450 reductase to the complex were investigated. In addition, the crystal structure of rat HO-1 in complex with ferrousα-verdoheme was determined.