Protein oxidation and peroxidation.
Protein oxidation and peroxidation.
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DOI：
10.1042/bj20151227
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发表时间：
2016-04-01
期刊：
影响因子：
--
通讯作者：
Davies MJ
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文献类型：
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作者：
Davies MJ
蛋白质是生物系统中自由基和双电子氧化剂的主要目标，因为它们的丰度和高反应速率常数。对于高活性自由基，损伤发生在多个侧链和主链位点。反应性较低的物种表现出更大的选择性方面的残基的目标和它们的空间位置。修饰可导致增加的侧链亲水性、侧链和主链片段化、经由共价交联或疏水相互作用的聚集、蛋白质解折叠和改变的构象、改变的与生物伴侣的相互作用和改变的转换。在O2存在的情况下，会形成大量的过氧化氢自由基和过氧化物（蛋白质过氧化）;后者占初始氧化剂通量的70%。蛋白质过氧化物可以氧化蛋白质和其他目标。单电子还原导致额外的自由基和与醇和羰基的链式反应作为主要产物;后者是蛋白质损伤的常用标记。甲硫氨酸残基的直接氧化是一个主要的反应;这通常比H2 O2更快，并导致蛋白质活性和功能的改变。与H2 O2不同，H2 O2可以被保护酶迅速去除，蛋白质过氧化物只能缓慢去除，而催化剂是主要的命运。虽然蛋白酶体和溶酶体酶以及其他蛋白酶（例如线粒体Lon）对修饰蛋白的周转可能是有效的，但蛋白质氢过氧化物抑制这些途径，这可能有助于修饰蛋白在细胞中的积累。现有证据支持蛋白质氧化和多种人类病理之间的关联，但这种联系是否是因果关系仍有待确定。
Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established.