鞘糖脂(GSL)是代表大部分鞘脂类的高度异质的脂质类别。GSL是细胞膜的基本成分,在各种生物过程中起关键作用,例如蜂窝信号,认可,和附着力。了解GSL的结构复杂性对于揭示其在生物学背景下的功能意义至关重要。特别是它们在各种疾病的病理生理学中的关键作用。质谱(MS)已成为GSL结构阐明的通用且不可或缺的工具,能够更深入地了解其复杂的分子结构及其在细胞动力学和病理生理学中的关键作用。这里,我们全面概述了为GSL分析量身定制的MS技术,强调它们在探测GSL复杂结构方面的效用,以促进我们对GSL在健康和疾病中的功能相关性的理解。使用多种片段化技术的串联MS的应用,包括新颖的离子活化方法,在研究聚糖序列时,连杆位置,和脂肪酸组成被广泛讨论。最后,我们应对当前的挑战,例如低丰度物种的检测和复杂光谱的解释,并通过改进MS仪器以提高灵敏度和分辨率,提供潜在解决方案和未来方向的见解,开发新的电离技术,或将MS与其他分析方法相结合,以实现全面的GSL表征。
Glycosphingolipids (GSL) are a highly heterogeneous class of lipids representing the majority of the sphingolipid category. GSL are fundamental constituents of cellular membranes that have key roles in various biological processes, such as cellular signaling, recognition, and adhesion. Understanding the structural complexity of GSL is pivotal for unraveling their functional significance in a biological context, specifically their crucial role in the pathophysiology of various diseases. Mass spectrometry (MS) has emerged as a versatile and indispensable tool for the structural elucidation of GSL enabling a deeper understanding of their complex molecular structures and their key roles in cellular dynamics and patholophysiology. Here, we provide a thorough overview of MS techniques tailored for the analysis of GSL, emphasizing their utility in probing GSL intricate structures to advance our understanding of the functional relevance of GSL in health and disease. The application of tandem MS using diverse fragmentation techniques, including novel ion activation methodologies, in studying glycan sequences, linkage positions, and fatty acid composition is extensively discussed. Finally, we address current challenges, such as the detection of low-abundance species and the interpretation of complex spectra, and offer insights into potential solutions and future directions by improving MS instrumentation for enhanced sensitivity and resolution, developing novel ionization techniques, or integrating MS with other analytical approaches for comprehensive GSL characterization.