Uceda Ana Belén, Mariño Laura, Casasnovas Rodrigo, Adrover Miquel
Departament de Química, Universitat de Les Illes Balears, Health Research Institute of the Balearic Islands (IdISBa), Ctra. Valldemossa Km 7.5, 07122 Palma, Spain.
Biophys Rev. 2024 Apr 12;16(2):189-218. doi: 10.1007/s12551-024-01188-4. eCollection 2024 Apr.
The formation of a heterogeneous set of advanced glycation end products (AGEs) is the final outcome of a non-enzymatic process that occurs in vivo on long-life biomolecules. This process, known as glycation, starts with the reaction between reducing sugars, or their autoxidation products, with the amino groups of proteins, DNA, or lipids, thus gaining relevance under hyperglycemic conditions. Once AGEs are formed, they might affect the biological function of the biomacromolecule and, therefore, induce the development of pathophysiological events. In fact, the accumulation of AGEs has been pointed as a triggering factor of obesity, diabetes-related diseases, coronary artery disease, neurological disorders, or chronic renal failure, among others. Given the deleterious consequences of glycation, evolution has designed endogenous mechanisms to undo glycation or to prevent it. In addition, many exogenous molecules have also emerged as powerful glycation inhibitors. This review aims to provide an overview on what glycation is. It starts by explaining the similarities and differences between glycation and glycosylation. Then, it describes in detail the molecular mechanism underlying glycation reactions, and the bio-molecular targets with higher propensity to be glycated. Next, it discusses the precise effects of glycation on protein structure, function, and aggregation, and how computational chemistry has provided insights on these aspects. Finally, it reports the most prevalent diseases induced by glycation, and the endogenous mechanisms and the current therapeutic interventions against it.
一组异质性晚期糖基化终产物（AGEs）的形成是在体内长寿生物分子上发生的非酶促过程的最终结果。这个过程称为糖基化，始于还原糖或其自氧化产物与蛋白质、DNA或脂质的氨基之间的反应，因此在高血糖条件下变得更加显著。一旦AGEs形成，它们可能会影响生物大分子的生物学功能，从而引发病理生理事件的发展。事实上，AGEs的积累已被指出是肥胖、糖尿病相关疾病、冠状动脉疾病、神经紊乱或慢性肾衰竭等疾病的触发因素。鉴于糖基化的有害后果，进化设计了内源性机制来逆转或预防糖基化。此外，许多外源性分子也已成为强大的糖基化抑制剂。本综述旨在概述什么是糖基化。首先解释糖基化和糖基化修饰之间的异同。然后，详细描述糖基化反应的分子机制以及更容易被糖基化的生物分子靶点。接下来，讨论糖基化对蛋白质结构、功能和聚集的精确影响，以及计算化学如何在这些方面提供见解。最后，报告由糖基化引起的最常见疾病，以及针对糖基化的内源性机制和当前的治疗干预措施。
