Chemical Biology of Reactive Sulfur Species: Hydrolysis-Driven Equilibrium of Polysulfides as a Determinant of Physiological Functions.
Chemical Biology of Reactive Sulfur Species: Hydrolysis-Driven Equilibrium of Polysulfides as a Determinant of Physiological Functions.
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DOI：
10.1089/ars.2021.0170
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发表时间：
2022-03
影响因子：
6.6
通讯作者：
Akaike T
中科院分区：
文献类型：
--
作者：
Sawa T;Takata T;Matsunaga T;Ihara H;Motohashi H;Akaike T
意义：多硫化物种类（即，R-Sn-R′，n > 2; R-Sn-H，n > 1）存在于许多生物中。氢过硫化物和氢多硫化物的高度亲核性质有助于多硫化物物种的有效抗氧化活性，保护生物体免受氧化和亲电子应激。最新进展：越来越多的证据表明，有机多硫化物（R-Sn-R′）很容易发生碱水解，从而形成亲核的氢硫化物/多硫化物（R-Sn−1H）和亲电子的次磺酸（R′SOH）物种。多硫化物即使在水性生理环境中也保持由水解驱动的稳态平衡。这种独特的性质使得多硫化物的化学和生物学比以前认为的更加复杂。关键问题：当亲电试剂存在时，多硫化物的水解平衡向右移动。强亲电烷基化剂（例如，单溴二氢化萘）极大地增强了多硫化物水解，这导致多硫化物降解增加和在不存在游离硫化氢的情况下双-S-二氢化萘加合物的人为形成。发现含羟基的物质如酪氨酸有效地保护多硫化物免于水解导致了新的烷基化剂N-碘乙酰基L-酪氨酸甲酯（TME-IAM）的开发。TME-IAM有效地和特异性地捕获和稳定氢化多硫化物并保护多硫化物链免于水解，并且当与质谱法一起使用时，TME-IAM允许反应性硫代谢物组的形态。此外，聚乙二醇共轭马来酰亚胺标记的凝胶迁移分析，它依赖于独特的水解平衡的多硫化物，将是一个可靠的技术，蛋白质组学的多硫化物含有的蛋白质。未来方向：使用精确的方法，以实现更好地了解多硫化物物种的发生和代谢是必要的，以深入了解多硫化物物种的未定义的生物学。抗氧化剂。氧化还原信号。36、327-336。
Significance: Polysulfide species (i.e., R-Sn-R′, n > 2; and R-Sn-H, n > 1) exist in many organisms. The highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to the potent antioxidant activities of polysulfide species that protect organisms against oxidative and electrophilic stresses. Recent Advances: Accumulating evidence suggests that organic polysulfides (R-Sn-R′) readily undergo alkaline hydrolysis, which results in formation of both nucleophilic hydrosulfide/polysulfide (R-Sn−1H) and electrophilic sulfenic acid (R′SOH) species. Polysulfides maintain a steady-state equilibrium that is driven by hydrolysis even in aqueous physiological milieus. This unique property makes polysulfide chemistry and biology more complex than previously believed. Critical Issues: The hydrolysis equilibrium of polysulfides shifts to the right when electrophiles are present. Strong electrophilic alkylating agents (e.g., monobromobimane) greatly enhance polysulfide hydrolysis, which leads to increased polysulfide degradation and artifactual formation of bis-S-bimane adducts in the absence of free hydrogen sulfide. The finding that hydroxyl group-containing substances such as tyrosine efficiently protected polysulfides from hydrolysis led to development of the new alkylating agent, N-iodoacetyl l-tyrosine methyl ester (TME-IAM). TME-IAM efficiently and specifically traps and stabilizes hydropolysulfides and protects polysulfide chains from hydrolysis, and, when used with mass spectrometry, TME-IAM allows speciation of the reactive sulfur metabolome. In addition, the polyethylene glycol-conjugated maleimide-labeling gel shift assay, which relies on unique hydrolysis equilibrium of polysulfides, will be a reliable technique for proteomics of polysulfide-containing proteins. Future Directions: Using precise methodologies to achieve a better understanding of the occurrence and metabolism of polysulfide species is necessary to gain insights into the undefined biology of polysulfide species. Antioxid. Redox Signal. 36, 327–336.