乙醛酸与α-胺基†上化学保护赖氨酸反应的质谱研究

IF 2.5 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Katarzyna Wrobel, Alma Rosa Corrales Escobosa, Francisco Javier Acevedo-Aguilar, Israel Enciso Donis and Kazimierz Wrobel
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引用次数: 0

摘要

Glyoxylic acid (GA)是一种可能参与糖基化过程的人体代谢物,被认为是nε -羧甲基赖氨酸(CML)的前体。根据反应条件的不同,GA与α-胺基化学保护赖氨酸或未保护赖氨酸的反应机理也有不同的报道。本研究的目的是阐明在生理pH值下发生的反应,使用质谱法和一些辅助工具。在第一种方法中,在水、甲醇及其混合物中发现了6种GA,其相对分布取决于溶剂组成。GA与z -赖氨酸(n - α-(carbobenzyloxy)- l -赖氨酸)反应的产物为Z-CML,两个参与GA的物质被指定为在甲醇中优先形成的物质。在pH为7.2的HEPES缓冲液中,使用高分辨率质谱分析100天内不同时间的反应混合物。质子化分子[M + H]+和相应的钠加合物([M + Na]+),它们的丰度随时间的变化以及MS/MS数据被用来分配反应中间体。采用液相色谱联用质谱法对关键中间体进行鉴定。在生理pH下,反应40天后检测Z-CML。提出了一种合理的反应机制,即GA与Z-Lys的ε-胺基之间形成加合物,然后经过两个脱羧步骤将醛基氧化为羧基或脱羧水解降解。Z-CML的缓慢形成归因于在所提出的反应方案中最终产物之前中间体的积累,表明氧化条件有利于Z-CML的产生,这与众所周知的氧化应激下AGEs的加速形成一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mass spectrometric study on the reaction of glyoxylic acid with chemically protected lysine at the α-amine group†

Mass spectrometric study on the reaction of glyoxylic acid with chemically protected lysine at the α-amine group†

Glyoxylic acid (GA) is a human metabolite potentially involved in glycation processes and is considered a precursor of Nε-carboxymethyl lysine (CML). Depending on the reaction conditions, different mechanisms of the reaction of GA with chemically protected lysine at the α-amine group or unprotected lysine have been reported. The objective of this study was to shed light on the reaction that occurs at physiological pH, using mass spectrometry and some complementary tools. In the first approach, six GA species were found in water, methanol and their mixtures with relative distribution depending on the solvent composition. The product of GA reaction with Z-Lys (Nα-(carbobenzyloxy)-L-lysine) was Z-CML, and two participating GA species were assigned to those preferentially formed in methanol. The reaction mixture in an HEPES buffer at pH 7.2 was analyzed using high-resolution MS at different times over 100 days. Protonated molecules [M + H]+ and respective sodium adducts ([M + Na]+), changes in their abundance over time and MS/MS data were used to assign the reaction intermediates. Additional experiments using liquid chromatography with MS were performed for the confirmation of key intermediates. At physiological pH, Z-CML was detected in the reaction mixture after 40 days. A plausible reaction mechanism was proposed, which involved the formation of adducts between GA species and the ε-amine group of Z-Lys, followed either by two decarboxylation steps and oxidation of the aldehyde group to carboxylic group or by decarboxylation and hydrolytic degradation. The slow formation of Z-CML was attributed to the accumulation of intermediates preceding the final product in the proposed reaction scheme, indicating that oxidative conditions would favor Z-CML production, which was in agreement with the well-known accelerated formation of AGEs under oxidative stress.

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来源期刊
New Journal of Chemistry
New Journal of Chemistry 化学-化学综合
CiteScore
5.30
自引率
6.10%
发文量
1832
审稿时长
2 months
期刊介绍: A journal for new directions in chemistry
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