Nitrite as a Substrate and Inhibitor of Myeloperoxidase
Nitrite as a Substrate and Inhibitor of Myeloperoxidase
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亚硝酸盐作为髓过氧化物酶的底物和抑制剂
DOI：
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发表时间：
2000
影响因子：
4.8
通讯作者：
A. Kettle
中科院分区：
文献类型：
--
作者：
C. V. van Dalen;C. Winterbourn;Revathy Senthilmohan;A. Kettle
髓过氧化物酶是嗜中性粒细胞的血红素酶，其使用过氧化氢将氯化物氧化成次氯酸。最近，它已被证明可以催化酪氨酸的硝化。在这项研究中，我们研究了它氧化亚硝酸盐和促进酪氨酰残基硝化的机制。亚硝酸盐被认为是一个穷人的髓过氧化物酶的底物，但其氯化活性的一个很好的抑制剂。亚硝酸盐通过将酶还原成无活性形式而减缓氯化，结果被氧化成二氧化氮。在生理浓度的亚硝酸盐和氯化物的存在下，髓过氧化物酶催化小硝化酪氨酰残基的七肽。然而，硝化的效率提高了至少4倍的游离酪氨酸。我们的数据与髓过氧化物酶将游离酪氨酸氧化为酪氨酰自由基并与肽中的酪氨酰残基交换的机制一致。这些肽基然后与二氧化氮偶联形成3-硝基酪氨酰残基。与中性粒细胞，髓过氧化物酶依赖的硝化需要高浓度的亚硝酸盐（1毫米），增加一倍的酪氨酸，并增加4倍的超氧化物歧化酶。超氧化物可能通过与二氧化氮和/或酪氨酰自由基反应来抑制硝化。我们认为，在炎症部位，髓过氧化物酶将硝酸蛋白质，即使亚硝酸盐是一个穷人的基板，因为共同基板酪氨酸将有助于反应。此外，当超氧化物浓度低时，3-硝基酪氨酸的产生将是最有利的。
Myeloperoxidase is a heme enzyme of neutrophils that uses hydrogen peroxide to oxidize chloride to hypochlorous acid. Recently, it has been shown to catalyze nitration of tyrosine. In this study we have investigated the mechanism by which it oxidizes nitrite and promotes nitration of tyrosyl residues. Nitrite was found to be a poor substrate for myeloperoxidase but an excellent inhibitor of its chlorination activity. Nitrite slowed chlorination by univalently reducing the enzyme to an inactive form and as a consequence was oxidized to nitrogen dioxide. In the presence of physiological concentrations of nitrite and chloride, myeloperoxidase catalyzed little nitration of tyrosyl residues in a heptapeptide. However, the efficiency of nitration was enhanced at least 4-fold by free tyrosine. Our data are consistent with a mechanism in which myeloperoxidase oxidizes free tyrosine to tyrosyl radicals that exchange with tyrosyl residues in peptides. These peptide radicals then couple with nitrogen dioxide to form 3-nitrotyrosyl residues. With neutrophils, myeloperoxidase-dependent nitration required a high concentration of nitrite (1 mm), was doubled by tyrosine, and increased 4-fold by superoxide dismutase. Superoxide is likely to inhibit nitration by reacting with nitrogen dioxide and/or tyrosyl radicals. We propose that at sites of inflammation myeloperoxidase will nitrate proteins, even though nitrite is a poor substrate, because the co-substrate tyrosine will be available to facilitate the reaction. Also, production of 3-nitrotyrosine will be most favorable when the concentration of superoxide is low.
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影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
影响因子：
15.9
作者：
Podrez, EA;Schmitt, D;Hazen, SL
通讯作者：
Hazen, SL
DOI：
10.1515/bchm3.1994.375.2.81
发表时间：
1994-02-01
期刊：
BIOLOGICAL CHEMISTRY HOPPE-SEYLER
影响因子：
--
作者：
BECKMANN, JS;YE, YZ;BECKMAN, JS
通讯作者：
BECKMAN, JS
影响因子：
3.9
作者：
Sampson, JB;Ye, YZ;Beckman, JS
通讯作者：
Beckman, JS
影响因子：
15.9
作者：
HADDAD, IY;PATAKI, G;MATALON, S
通讯作者：
MATALON, S