{"title":"Structure selective fragment ions of epoxidized sphingolipids","authors":"Jing Yu , Sven Heiles","doi":"10.1016/j.ijms.2025.117483","DOIUrl":null,"url":null,"abstract":"<div><div>Sphingolipids are essential building blocks of most organisms. The structure of sphingolipids is tightly regulated and dysregulation during diseases can result in altered sphingolipid structures. In this manuscript, we explore the potential of sphingolipid epoxidation for the assignment and discrimination of sphingolipid structures. Employing shotgun tandem mass spectrometry, liquid chromatography tandem mass spectrometry, authentic sphingolipid standards, and density function theory, we demonstrate that epoxidation of shingoid bases (SPBs), ceramides, and sphingomyelins facilitates C=C bond (DB) position assignment. This includes DBs in the N-linked fatty acyl moiety and the sphingoid base. For SPBs with DBs at position 4, a major component for almost all sphingolipids, we furthermore demonstrate that the fragmentation pathway differs for this DB position compared to other DB-diagnostic fragment ions. We show that epoxidation of this DB position facilities intramolecular rearrangement and formation of distinct diagnostic fragment ions. To demonstrate the analytical capabilities and show that the 4 SPB DBs enable confident differentiation of ceramides and dihydroceramides, results for brain ceramide extract are presented. The identified fragmentation pathway for 4 SPB DB ions in combination with N-acyl assignment and DB position assignment allows to annotate 25 ceramide/dihydroceramide compounds in the brain ceramide extract out of which 23 are DB position isomers.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"515 ","pages":"Article 117483"},"PeriodicalIF":1.6000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Mass Spectrometry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1387380625000879","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHYSICS, ATOMIC, MOLECULAR & CHEMICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Sphingolipids are essential building blocks of most organisms. The structure of sphingolipids is tightly regulated and dysregulation during diseases can result in altered sphingolipid structures. In this manuscript, we explore the potential of sphingolipid epoxidation for the assignment and discrimination of sphingolipid structures. Employing shotgun tandem mass spectrometry, liquid chromatography tandem mass spectrometry, authentic sphingolipid standards, and density function theory, we demonstrate that epoxidation of shingoid bases (SPBs), ceramides, and sphingomyelins facilitates C=C bond (DB) position assignment. This includes DBs in the N-linked fatty acyl moiety and the sphingoid base. For SPBs with DBs at position 4, a major component for almost all sphingolipids, we furthermore demonstrate that the fragmentation pathway differs for this DB position compared to other DB-diagnostic fragment ions. We show that epoxidation of this DB position facilities intramolecular rearrangement and formation of distinct diagnostic fragment ions. To demonstrate the analytical capabilities and show that the 4 SPB DBs enable confident differentiation of ceramides and dihydroceramides, results for brain ceramide extract are presented. The identified fragmentation pathway for 4 SPB DB ions in combination with N-acyl assignment and DB position assignment allows to annotate 25 ceramide/dihydroceramide compounds in the brain ceramide extract out of which 23 are DB position isomers.
期刊介绍:
The journal invites papers that advance the field of mass spectrometry by exploring fundamental aspects of ion processes using both the experimental and theoretical approaches, developing new instrumentation and experimental strategies for chemical analysis using mass spectrometry, developing new computational strategies for data interpretation and integration, reporting new applications of mass spectrometry and hyphenated techniques in biology, chemistry, geology, and physics.
Papers, in which standard mass spectrometry techniques are used for analysis will not be considered.
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