Wilks A, Torpey J, Ortiz de Montellano P R
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446.
J Biol Chem. 1994 Nov 25;269(47):29553-6.
Previous studies have established that reaction of the rat heme-heme oxygenase complex with H2O2 proceeds normally to give verdoheme, whereas reaction of the complex with meta-chloroperbenzoic acid yields a ferryl (FeIV = O) species and a protein radical but no verdoheme. The heme-heme oxygenase complex is shown here to react regiospecifically with ethyl hydroperoxide to give alpha-meso-ethoxyheme. Formation of this product exactly parallels the formation of alpha-meso-hydroxyheme in the normal reaction supported by cytochrome P450 reductase/NADPH or H2O2. These results rule out a nucleophilic mechanism for the alpha-meso-hydroxylation catalyzed by heme oxygenase and indicate that it involves electrophilic (or possibly radical) addition of the distal oxygen of iron-bound peroxide (FeIII-OOH) to the porphyrin ring.
先前的研究已证实，大鼠血红素 - 血红素加氧酶复合物与过氧化氢反应能正常生成胆绿素，而该复合物与间氯过氧苯甲酸反应则产生高铁（FeIV = O）物种和蛋白质自由基，但无胆绿素。本文显示，血红素 - 血红素加氧酶复合物与氢过氧化乙酯发生区域特异性反应生成α - 中 - 乙氧基血红素。该产物的形成与细胞色素P450还原酶/NADPH或过氧化氢支持的正常反应中α - 中 - 羟基血红素的形成完全平行。这些结果排除了血红素加氧酶催化α - 中 - 羟基化的亲核机制，并表明其涉及铁结合过氧化物（FeIII - OOH）的远端氧向卟啉环的亲电（或可能是自由基）加成。
