Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages.
Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages.
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DOI：
10.1016/s0021-9258(18)53581-x
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发表时间：
1993-02
期刊：
影响因子：
--
通讯作者：
J. Heinecke;Wei Li;Henry L. Daehnke;J. Goldstein
中科院分区：
文献类型：
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作者：
J. Heinecke;Wei Li;Henry L. Daehnke;J. Goldstein
髓过氧化物酶由活化的吞噬细胞分泌，由H2 O2和Cl-产生强有力的细胞毒素次氯酸。我们表明，该酶也可以利用过氧化氢氧化L-酪氨酸酪氨酸自由基，产生稳定的交联产物二酪氨酸。由髓过氧化物酶-H_2O_2系统合成的酪氨酸不需要卤化物，并被Cl ~-部分抑制。在生理浓度的Cl-，L-酪氨酸，和其他血浆氨基酸，纯化的髓过氧化物酶利用26%的H2 O2的反应混合物中形成二酪氨酸。氨基三唑、氰化物和叠氮化物抑制反应。佛波酯刺激的人中性粒细胞和单核细胞衍生的巨噬细胞类似地通过过氧化氢酶、氨基三唑和叠氮化物抑制的途径从L-酪氨酸产生二酪氨酸。对H2 O2的需求和血红素毒物的抑制表明活化的吞噬细胞通过过氧化机制合成二酪氨酸。这些结果表明，L-酪氨酸可以有效地竞争与Cl-作为底物的髓过氧化物酶和提高的可能性，形成酪氨酰自由基可能发挥作用的吞噬细胞的炎症反应。因为二酪氨酸是抗蛋白酶的，对酸水解稳定，并且具有强烈的荧光，所以其在组织中的鉴定可以精确定位吞噬细胞在体内造成氧化损伤的靶点。
Myeloperoxidase, secreted by activated phagocytes, produces the powerful cytotoxin hypochlorous acid from H2O2 and Cl-. We show that the enzyme can also employ H2O2 to oxidize L-tyrosine to tyrosyl radical, yielding the stable cross-linked product dityrosine. Dityrosine synthesis by the myeloperoxidase-H2O2 system did not require halide and was partially inhibited by Cl-. At physiological concentrations of Cl-, L-tyrosine, and other plasma amino acids, purified myeloperoxidase utilized 26% of the H2O2 in the reaction mixture to form dityrosine. Aminotriazole, cyanide, and azide inhibited the reaction. Phorbol ester-stimulated human neutrophils and monocyte-derived macrophages similarly generated dityrosine from L-tyrosine by a pathway inhibited by catalase, aminotriazole, and azide. The requirement for H2O2 and the inhibition by heme poisons suggest that activated phagocytes synthesize dityrosine by a peroxidative mechanism. These results indicate that L-tyrosine can compete effectively with Cl- as a substrate for myeloperoxidase and raise the possibility that formation of tyrosyl radical may play a role in the phagocyte inflammatory response. Because dityrosine is protease-resistant, stable to acid hydrolysis, and intensely fluorescent, its identification in tissues may pinpoint targets where phagocytes inflict oxidative damage in vivo.