Department of Biotechnology, Integral University, Lucknow, India.
PLoS One. 2013 Sep 4;8(9):e72128. doi: 10.1371/journal.pone.0072128. eCollection 2013.
Non-enzymatic glycation is the addition of free carbonyl group of reducing sugar to the free amino groups of proteins, resulting in the formation of a Schiff base and an Amadori product. Dihydroxyacetone (DHA) is one of the carbonyl species which reacts rapidly with the free amino groups of proteins to form advanced glycation end products (AGEs). The highly reactive dihydroxyacetone phosphate is a derivative of dihydroxyacetone (DHA), and a product of glycolysis, having potential glycating effects to form AGEs. The formation of AGEs results in the generation of free radicals which play an important role in the pathophysiology of aging and diabetic complications. While the formation of DHA-AGEs has been demonstrated previously, no extensive studies have been performed to assess the inhibition of AGE inhibitors at all the three stages of glycation (early, intermediate and late) using metformin (MF) and pyridoxamine (PM) as a novel inhibitor.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we report glycation of human serum albumin (HSA) & its characterization by various spectroscopic techniques. Furthermore, inhibition of glycation products at all the stages of glycation was also studied. Spectroscopic analysis suggests structural perturbations in the HSA as a result of modification which might be due to generation of free radicals and formation of AGEs.
The inhibition in the formation of glycation reaction reveals that Pyridoxamine is a better antiglycating agent than Metformin at all stages of the glycation (early, intermediate and late stages).
非酶糖基化是指还原糖的自由羰基与蛋白质的游离氨基之间的加成反应，生成希夫碱和阿玛多里产物。二羟丙酮（DHA）是与蛋白质的游离氨基快速反应形成晚期糖基化终末产物（AGEs）的羰基物质之一。高度反应性的二羟丙酮磷酸是二羟丙酮（DHA）的衍生物，也是糖酵解的产物，具有潜在的糖化作用，形成 AGEs。AGEs 的形成导致自由基的产生，自由基在衰老和糖尿病并发症的病理生理学中起着重要作用。虽然已经证明了 DHA-AGEs 的形成，但没有广泛的研究评估二甲双胍（MF）和吡哆胺（PM）作为新型抑制剂在糖化的所有三个阶段（早期、中期和晚期）对 AGE 抑制剂的抑制作用。
方法/主要发现：在这项研究中，我们报告了人血清白蛋白（HSA）的糖化及其通过各种光谱技术进行的表征。此外，还研究了所有糖化阶段的糖化产物的抑制作用。光谱分析表明，HSA 的结构发生了修饰引起的扰动，这可能是由于自由基的产生和 AGEs 的形成。
糖化反应形成的抑制作用表明，吡哆胺在糖化的所有阶段（早期、中期和晚期）都比二甲双胍更能抑制糖化。
