Abstract:
Aberrant expression of glycosphingolipids has been implicated in a myriad of diseases, but our understanding of the strucural diversity, spatial distribution, and biological function of this class of biomolecules remains limited. These challenges partly stem from a lack of sensitive tools that can detect, identify, and quantify glycosphingolipids at the molecular level. Mass spectrometry has emerged as a powerful tool poised to address most of these challenges. Here, we review the recent developments in analytical glycosphingolipidomics with an emphasis on sample preparation, mass spectrometry and tandem mass spectrometry-based structural characterization, label-free and labeling-based quantification. We also discuss the nomenclature of glycosphingolipids, and emerging technologies like ion mobility spectrometry in differentiation of glycosphingolipid isomers. The intrinsic advantages and shortcomings of each method are carefully critiqued in line with an individual\'s research goals. Finally, future perspectives on analytical sphingolipidomics are stated, including a need for novel and more sensive methods in isomer separation, low abundance species detection, and profiling the spatial distribution of glycosphingolipid molecular species in cells and tissues using imaging mass spectrometry.
摘要:
鞘糖脂的异常表达与无数疾病有关,但是我们对结构多样性的理解,空间分布,这类生物分子的生物学功能仍然有限。这些挑战部分源于缺乏能够检测的敏感工具,identify,并在分子水平上量化鞘糖脂。质谱已经成为一种强大的工具,可以解决大多数这些挑战。这里,我们回顾了分析性鞘糖脂组学的最新进展,重点是样品制备,基于质谱和串联质谱的结构表征,无标签和基于标签的定量。我们还讨论了鞘糖脂的命名法,以及离子迁移谱等新兴技术在鞘糖脂异构体分化中的应用。根据个人的研究目标,对每种方法的内在优点和缺点进行了仔细的批判。最后,阐述了分析鞘脂组学的未来观点,包括在异构体分离中需要新颖和更灵敏的方法,低丰度物种检测,并使用成像质谱法分析细胞和组织中鞘糖脂分子种类的空间分布。