Horse Heart Myoglobin Catalyzes the H2O2-Dependent Oxidative Dehalogenation of Chlorophenols to DNA-Binding Radicals and Quinones

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• 作者：Robert L. Osborne ; Michael K. Coggins ; Mike Walla ; John H. Dawson
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：August 28, 2007
• 年：2007
• 卷：46
• 期：34
• 页码：9823 - 9829
• 全文大小：130K
• 年卷期：v.46,no.34(August 28, 2007)
• ISSN：1520-4995

文摘

The heme-containing respiratory protein, myoglobin (Mb), best known for oxygen storage,can exhibit peroxidase-like activity under conditions of oxidative stress. Under such circumstances, theinitially formed ferric state can react with H₂O₂ (or other peroxides) to generate a long-lived ferryl[Fe(IV)=O] Compound II (Cpd II) heme intermediate that is capable of oxidizing a variety of biomolecules.In this study, the ability of Mb Cpd II to catalyze the oxidation of carcinogenic halophenols is demonstrated.Specifically, 2,4,6-trichlorophenol (TCP) is converted to 2,6-dichloro-1,4-benzoquinone in a H₂O₂-dependentprocess. The fact that Mb Cpd II is an active oxidant in halophenol dehalogenation is consistent with atraditional peroxidase order of addition of H₂O₂ followed by TCP. With 4-chlorophenol, a dimerizedproduct is formed, consistent with a mechanism involving generation of a reactive phenoxy radicalintermediate by an electron transfer process. The radical nature of this process may be physiologicallyrelevant since recent studies have revealed that phenoxy radicals and electrophilic quinones, specificallyof the type described herein, covalently bind to DNA [Dai, J., Sloat, A. L., Wright, M. W., and Manderville,R. A. (2005) Chem. Res. Toxicol. 18, 771-779]. Thus, the stability of Mb Cpd II and its ability to oxidizeTCP may explain why such compounds are carcinogenic. Furthermore, the initial rate of dehalogenationcatalyzed by Mb Cpd II is nearly comparable to that of the same reaction carried out by turnover of theferric state, demonstrating the potential physiological danger of this long-lived, high-valent intermediate.