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Influence of Transketolase-Catalyzed Reactions on the Formation of Glycolaldehyde and Glyoxal Specific Posttranslational Modifications under Physiological Conditions
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2018-02-05 00:00:00 , DOI: 10.1021/acs.jafc.7b05472 Alexander Klaus 1 , Tim Baldensperger 1 , Roman Fiedler 2 , Matthias Girndt 2 , Marcus A. Glomb 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2018-02-05 00:00:00 , DOI: 10.1021/acs.jafc.7b05472 Alexander Klaus 1 , Tim Baldensperger 1 , Roman Fiedler 2 , Matthias Girndt 2 , Marcus A. Glomb 1
Affiliation
In the present study, we investigated the role of transketolase (TK) in the modulation of glycolaldehyde driven Maillard reactions. In vitro experiments with recombinant human TK reduced glycolaldehyde and glyoxal induced carbonyl stress and thereby suppressed the formation of advanced glycation endproducts up to 70% due to the enzyme-catalyzed conversion of glycolaldehyde to erythrulose. This was further substantiated by the use of 13C-labeled compounds. For the first time, glycolaldehyde and other sugars involved in the TK reaction were quantified in vivo and compared to nondiabetic uremic patients undergoing hemodialysis. Quantitation revealed amounts of glycolaldehyde up to 2 μM and highlighted its crucial role in the formation of AGEs in vivo. In this context, a LC–MS2 method for the comprehensive detection of sedoheptulose-7-phosphate, fructose-6-phosphate, ribose-5-phosphate, erythrose-4-phosphate, erythrulose, and glycolaldehyde in whole blood, plasma, and red blood cells was established and validated based on derivatization with 1-naphthylamine and sodium cyanoborohydride.
中文翻译:
在生理条件下,转酮醇酶催化的反应对乙醇醛的形成和乙二醛特异的翻译后修饰的影响
在本研究中,我们调查了转酮醇酶(TK)在乙醇醛驱动的美拉德反应的调节中的作用。重组人TK的体外实验减少了乙醇醛和乙二醛诱导的羰基应力,从而由于酶催化的乙醇醛向赤藓糖的转化,抑制了高达70%的高级糖基化终产物的形成。通过使用13 C标记的化合物进一步证实了这一点。首次对体内与TK反应有关的乙醇醛和其他糖类进行了体内定量,并与进行血液透析的非糖尿病尿毒症患者进行了比较。定量揭示了高达2μM的乙醇醛含量,并强调了其在AGEs形成中的关键作用体内。在这种情况下,采用LC-MS 2方法可对全血,血浆和血浆中的七磷酸七庚酯,6-磷酸果糖,5-磷酸核糖,-4-磷酸赤藓糖,赤藓糖和乙醇醛进行全面检测。基于1-萘胺和氰基硼氢化钠的衍生化,建立并验证了红细胞。
更新日期:2018-02-05
中文翻译:
在生理条件下,转酮醇酶催化的反应对乙醇醛的形成和乙二醛特异的翻译后修饰的影响
在本研究中,我们调查了转酮醇酶(TK)在乙醇醛驱动的美拉德反应的调节中的作用。重组人TK的体外实验减少了乙醇醛和乙二醛诱导的羰基应力,从而由于酶催化的乙醇醛向赤藓糖的转化,抑制了高达70%的高级糖基化终产物的形成。通过使用13 C标记的化合物进一步证实了这一点。首次对体内与TK反应有关的乙醇醛和其他糖类进行了体内定量,并与进行血液透析的非糖尿病尿毒症患者进行了比较。定量揭示了高达2μM的乙醇醛含量,并强调了其在AGEs形成中的关键作用体内。在这种情况下,采用LC-MS 2方法可对全血,血浆和血浆中的七磷酸七庚酯,6-磷酸果糖,5-磷酸核糖,-4-磷酸赤藓糖,赤藓糖和乙醇醛进行全面检测。基于1-萘胺和氰基硼氢化钠的衍生化,建立并验证了红细胞。