Ge Fei, Jian Jingai, Li Na, Yang Jingzhi, Chao Yufan, Dong Xin
Mental Health Center Affiliated to Shanghai University School of Medicine, Shanghai, 200083, China; School of Medicine, Shanghai University, Shanghai, 200444, China; Department of Pharmacology, Cardiac and Cerebrovascular Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510000, China.
School of Medicine, Shanghai University, Shanghai, 200444, China.
Anal Chim Acta. 2025 Jul 8;1358:344099. doi: 10.1016/j.aca.2025.344099. Epub 2025 Apr 20.
Ceramides (Cers) play a crucial role in sphingolipid metabolism with multiple biological activities and functions. Due to the high regularity and variability of their structures, there exist thousands of possible Cers. The structural diversity endows them with various biological functions but also poses significant challenges for qualitative and quantitative analysis. The lack of in-depth characterization methods for such lipids resulted in only a small fraction of Cers being reported, severely hindering the exploration of their biological functions and activities. This work presented a lipid analysis method based on a liquid chromatography-mass spectrometry platform, enabling the accurate quantification of 337 Cers simultaneously. Supported by a mathematical model, this work succeeded in generating a quadratic equation relationship between retention time and Cers carbon number. Subsequently, this method was applied to the large-scale quantitative detection of Cers in serum samples from Alzheimer's disease (AD) patients, identifying and characterizing 62 differential Cers. These could potentially serve as serum biomarkers for AD diagnosis. This study demonstrates a strategy for the large-scale in-depth characterization of complex endogenous lipid molecules with highly variable and regular structures in the absence of sufficient commercial standard materials. This work provides a novel analysis method and reference for exploring and developing the functions of such endogenous bioactive molecules.
神经酰胺（Cers）在鞘脂代谢中发挥着关键作用，具有多种生物学活性和功能。由于其结构具有高度规律性和变异性，可能存在数千种不同的神经酰胺。结构多样性赋予了它们各种生物学功能，但也给定性和定量分析带来了重大挑战。由于缺乏针对此类脂质的深入表征方法，仅有一小部分神经酰胺被报道，这严重阻碍了对其生物学功能和活性的探索。这项工作提出了一种基于液相色谱 - 质谱平台的脂质分析方法，能够同时对337种神经酰胺进行准确定量。在一个数学模型的支持下，这项工作成功建立了保留时间与神经酰胺碳原子数之间的二次方程关系。随后，该方法被应用于阿尔茨海默病（AD）患者血清样本中神经酰胺的大规模定量检测，鉴定并表征了62种差异神经酰胺。这些神经酰胺有可能作为AD诊断的血清生物标志物。本研究展示了一种在缺乏足够商业标准物质的情况下，对结构高度可变且具有规律性的复杂内源性脂质分子进行大规模深入表征的策略。这项工作为探索和开发此类内源性生物活性分子的功能提供了一种新颖的分析方法和参考。
