Institute of Analytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Germany.
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Germany; Department of Biochemistry, St. Petersburg State University, Russia.
Food Chem. 2021 Jun 15;347:128951. doi: 10.1016/j.foodchem.2020.128951. Epub 2020 Dec 27.
Glycation is referred to as the interaction of protein amino and guanidino groups with reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end-products (AGEs) contribute to pathogenesis of diabetes mellitus and neurodegenerative disorders. Upon their intestinal absorption, dietary sugars and α-dicarbonyl compounds interact with blood proteins yielding AGEs. Although the differences in glycation potential of monosaccharides are well characterized, the underlying mechanisms are poorly understood. To address this question, d-glucose, d-fructose and l-ascorbic acid were incubated with human serum albumin (HSA). The sugars and α-dicarbonyl intermediates of their degradation were analyzed in parallel to protein glycation patterns (exemplified with hydroimidazolone modifications of arginine residues and products of their hydrolysis) by bottom-up proteomics and computational chemistry. Glycation of HSA with sugars revealed 9 glyoxal- and 14 methylglyoxal-derived modification sites. Their dynamics was sugar-specific and depended on concentrations of α-dicarbonyls, their formation kinetics, and presence of stabilizing residues in close proximity to the glycation sites.
糖基化是指蛋白质的氨基和胍基与还原糖及其降解产物的羰基发生相互作用。由此产生的晚期糖基化终末产物（AGEs）是导致糖尿病和神经退行性疾病发病的原因之一。在肠道吸收过程中，饮食中的糖和α-二羰基化合物与血液蛋白相互作用生成 AGEs。尽管单糖的糖化潜力差异很大，但相关的潜在机制尚不清楚。为了解决这个问题，我们用人类血清白蛋白（HSA）孵育了 d-葡萄糖、d-果糖和 l-抗坏血酸。通过自上而下的蛋白质组学和计算化学分析，与蛋白质糖化模式（以精氨酸残基的水解产物和羟咪唑啉酮修饰为例）平行分析了糖和 α-二羰基化合物的降解中间产物。用糖对 HSA 进行糖化，揭示了 9 个来自甘油醛和 14 个来自甲基乙二醛的修饰位点。它们的动力学是糖特异性的，取决于 α-二羰基化合物的浓度、它们的形成动力学以及靠近糖化位点的稳定残基的存在。
