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首页> 外文期刊>Biochemistry >Myeloperoxidase-Induced Oxidation of Albumin and Ceruloplasmin: Role of Tyrosines
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Myeloperoxidase-Induced Oxidation of Albumin and Ceruloplasmin: Role of Tyrosines

机译:肌释氧基酶诱导的白蛋白和刺激素:酪氨酸的作用

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Neutrophil myeloperoxidase (MPO) plays an important role in protecting the body against infections. MPO products-hypohalous acids and phenoxyl radicals-are strong oxidants that can damage not only foreign intruders but also host tissues, including blood plasma proteins. Here, we compared the MPO-induced oxidation of two plasma proteins with antioxidant properties-human serum albumin (HSA) and ceruloplasmin (CP). Incubation of both proteins with hypochlorite (NaOCl) or catalytically active MPO (MPO + H2O2), which synthesizes hypochlorous acid (HOCl) in the presence of chloride ions, resulted in the quenching of protein tryptophan fluorescence. Oxidation-induced changes in the structures of HSA and CP were different. HSA efficiently neutralized MPO-generated oxidants without protein aggregation, while CP oxidation resulted in the formation of large aggregates stabilized by strong covalent bonds between the aromatic amino acid residues. Tyrosine is present in the plasma as free amino acid and also as a component of the polypeptide chains of the proteins. The number of tyrosine residues in a protein does not determine its propensity for aggregate formation. In the case of C P, protein aggregation was primarily due to the high content of tryptophan residues in its polypeptide chain. MPO-dependent oxidation of free tyrosine results in the formation of tyrosyl radicals, that do not oxidize aromatic amino acid residues in proteins because of the high rate of recombination with dityrosine formation. At the same time, free tyrosine can influence MPO-induced protein oxidation due to its ability to modulate HOCl synthesis in the MPO active site.
机译:中性粒细胞髓氧化酶(MPO)在保护身体免受感染方面发挥着重要作用。 MPO产物 - 低开香酸和苯氧基 - 是强氧化剂,不仅可以损坏异物入侵者,而且可以损坏宿主组织,包括血浆蛋白质。在此,我们将MPO诱导的两种血浆蛋白质氧化与抗氧化性能 - 人血清白蛋白(HSA)和刺纤蛋白(CP)进行比较。用次氯酸盐(NaOCl)或催化活性MPO(MPO + H 2 O 2)孵育两种蛋白质,其在氯离子存在下合成次氯酸(HOCl),导致蛋白质色氨酸荧光的猝灭。 HSA和Cp结构的氧化诱导的变化是不同的。 HSA有效地中和MPO产生的氧化剂而没有蛋白质聚集,而CP氧化导致通过芳族氨基酸残基之间的强共价键稳定的大聚集体。酪氨酸存在于血浆中作为游离氨基酸,也作为蛋白质的多肽链的组分。蛋白质中的酪氨酸残基的数量不确定其骨料形成的倾向。在C p的情况下,蛋白质聚集主要是由于其多肽链中的色氨酸残留物的高含量。自由酪氨酸的MPO依赖性氧化导致酪棒的形成,由于具有抗核形成的重组速率高,因此不会氧化蛋白质中的芳族氨基酸残基。同时,由于其调节MPO活性位点中的HoCl合成能力,游离酪氨酸可以影响MPO诱导的蛋白质氧化。

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