Al-Abed Y, Liebich H, Voelter W, Bucala R
Picower Institute for Medical Research, Manhasset, New York 11030, USA.
J Biol Chem. 1996 Feb 9;271(6):2892-6. doi: 10.1074/jbc.271.6.2892.
Advanced glycosylation end products (AGEs) have been identified to be present on both the apolipoprotein and lipid components of low density lipoprotein (LDL) and to act to prevent its recognition and uptake by high affinity, tissue LDL receptors. Lipid-linked AGEs form readily in vitro by the covalent addition of glucose to the amine-containing head groups of phospholipids. This process is accompanied by oxidation of the unsaturated fatty acid side chains and occurs in the absence of exogenously added transition metals or free radical generating systems, suggesting that AGE formation may contribute significantly to lipid oxidation in vivo. To assess more precisely the chemical basis of AGE-induced oxidative modification, we performed gas chromatography-mass spectrometry analysis of the lipid products which form over time during LDL-advanced glycosylation in vitro. Negative ion chemical ionization mass spectroscopy of two major compounds that were identified were consistent with the structures of the fatty acid oxidation products 4-hydroxyhexenal and 4-hydroxynonenal. These data support the concept that AGE formation in close proximity to unsaturated fatty acyl groups leads to lipid oxidation and provide additional evidence that advanced glycosylation is an important pathogenic modification of the LDL particle in vivo.
晚期糖基化终产物（AGEs）已被证实存在于低密度脂蛋白（LDL）的载脂蛋白和脂质成分上，并会阻止其被高亲和力的组织LDL受体识别和摄取。脂质连接的AGEs在体外可通过葡萄糖与磷脂含胺头部基团的共价加成而轻易形成。此过程伴随着不饱和脂肪酸侧链的氧化，且在未添加外源过渡金属或自由基生成系统的情况下发生，这表明AGE的形成可能在体内脂质氧化过程中起重要作用。为更精确地评估AGE诱导的氧化修饰的化学基础，我们对体外LDL晚期糖基化过程中随时间形成的脂质产物进行了气相色谱 - 质谱分析。所鉴定出的两种主要化合物的负离子化学电离质谱与脂肪酸氧化产物4 - 羟基己烯醛和4 - 羟基壬烯醛的结构一致。这些数据支持了不饱和脂肪酰基附近AGE的形成会导致脂质氧化这一概念，并提供了额外证据表明晚期糖基化是体内LDL颗粒的一种重要致病修饰。
