Copper-Catalyzed Tyrosine Nitration

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• 作者：Liang Qiao ; Yu Lu ; Baohong Liu ; Hubert H. Girault
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：December 14, 2011
• 年：2011
• 卷：133
• 期：49
• 页码：19823-19831
• 全文大小：1029K
• 年卷期：v.133,no.49(December 14, 2011)
• ISSN：1520-5126

文摘

Tyrosine nitration, often observed during neurodegenerative disorders under nitrative stress, is usually considered to be induced chemically either by nitric oxide and oxygen forming nitrogen dioxide or by the decomposition of peroxynitrite. It can also be induced enzymatically by peroxidases or superoxide dismutases in the presence of both hydrogen peroxide and nitrite forming nitrogen dioxide and/or peroxynitrite. In this study, the role of cupric ions for catalyzing tyrosine nitration in the presence of hydrogen peroxide and nitrite, by a chemical mechanism rather similar to enzymatic pathways where nitrite is oxidized to form nitrogen dioxide, was investigated by development of a microreactor also capable of acting as an emitter for electrospray ionization mass spectrometry analysis. Indeed, cupric ions and peptide鈥揷upric ion complexes are found to be excellent Fenton catalysts, even better than Fe(III) or heme, for the formation of ^{鈥?/sup>OH radicals and/or copper(II)-bound 鈥?/sup>OH radicals from hydrogen peroxide. These radicals are efficiently scavenged by nitrite anions to form 鈥?/sup>NO₂ and by tyrosine to form tyrosine radicals, leading to tyrosine nitration in polypeptides. We also show that cupric ions can catalyze tyrosine nitration from nitric oxide, oxygen, and hydrogen peroxide as the formation of tyrosine radicals is increased in the presence of diffusible and/or copper(II) bound hydroxyl radicals. This study shows that copper has a polyvalent role in the processes of tyrosine nitration.}