Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34
Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34
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DOI：
10.1111/febs.14609
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发表时间：
2018-09-01
期刊：
影响因子：
5.4
通讯作者：
Ricci, Giorgio
中科院分区：
文献类型：
--
作者：
Bocedi, Alessio;Cattani, Giada;Ricci, Giorgio
人血清白蛋白（HSA）的特征在于17个二硫化物和仅一个未配对的半胱氨酸（Cys（34）），其在还原的白蛋白中可以是游离的，或在氧化的白蛋白中作为混合二硫化物与半胱氨酸连接，或少量与其他天然硫醇连接。在健康受试者中，氧化形式的水平约为35%，但在氧化损伤后或患有肾脏疾病的患者中，它上升至70%。因此，氧化白蛋白被认为是氧化应激的短期生物标志物，因为其水平可能在离散时间跨度内在适当的氧化还原输入下增加或减少。本文首次确定了人血清白蛋白（HSA）还原态和氧化态半胱氨酸（34）与天然二硫化物和硫醇反应的动力学性质。动力学常数支持的证据，在体内观察到的半胱氨酸（34）氧化还原振荡主要是由于与半胱氨酸和胱氨酸的相互作用，没有任何酶的支持参与。这项研究也给出了一个合理的解释，没有参与的17个二硫化物天然存在于HSA在这些氧化还原转换。半胱氨酸的这种惰性行为在一定程度上是由于这些键的溶剂可及性或柔性因素，但主要是由于它们强的热力学稳定性，这本质上是由邻近效应引起的。类似的机制可能在许多蛋白质中起作用，这些蛋白质在还原介质（如胞质溶胶）中维持二硫键。
Human serum albumin (HSA) is characterized by 17 disulfides and by only one unpaired cysteine (Cys(34)), which can be free in the reduced albumin or linked as a mixed disulfide with cysteine, or in minor amount with other natural thiols, in the oxidized albumin. In healthy subjects, the level of the oxidized form is about 35%, but it rises up to 70% after oxidative insults or in patients with kidney diseases. Oxidized albumin is therefore considered a short-term biomarker of oxidative stress as its level may increase or decrease under appropriate redox inputs in discrete temporal spans. This paper defines, for the first time, the kinetic properties of reduced and oxidized Cys(34) of HSA in their reactions with natural disulfides and thiols. Kinetic constants support the evidence that the Cys(34) redox oscillations observed in vivo are mainly due to the interaction with cysteine and cystine without the involvement of any enzymatic support. This study gives also a plausible explanation for the absence of involvement of the 17 disulfides naturally present in HSA in these redox transitions. This inert behavior toward cysteine is marginally due to solvent accessibility or flexibility factors of these bonds but mainly to their strong thermodynamic stability, which is caused essentially by a proximity effect. A similar mechanism is likely at play in the many proteins that maintain disulfide bridges in a reducing medium like the cytosol.