Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms <s> Introduction <s> Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding pro- teins, and receptors. A comprehensive analysis of lipid mol- ecules, "lipidomics," in the context of genomics and pro- teomics is crucial to understanding cellular physiology and pathology; consequently, lipid biology has become a major research target of the postgenomic revolution and systems biology. To facilitate international communication about lip- ids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by our lipid community. As an initial step in this development, we divide lipids into eight catego- ries (fatty acyls, glycerolipids, glycerophospholipids, sphin- golipids, sterol lipids, prenol lipids, saccharolipids, and poly- ketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical struc- tures of individual lipids and their derivatives, and provide a 12 digit identifier for each unique lipid molecule. The lipid classification scheme is chemically based and driven by the distinct hydrophobic and hydrophilic elements that com- pose the lipid. This structured vocabulary will facilitate the systematization of lipid biology and enable the cataloging of lipids and their properties in a way that is compatible with <s> BIB001 </s> Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms <s> Introduction <s> Signalling lipids such as eicosanoids, phosphoinositides, sphingolipids and fatty acids control important cellular processes, including cell proliferation, apoptosis, metabolism and migration. Extracellular signals from cytokines, growth factors and nutrients control the activity of a key set of lipid-modifying enzymes: phospholipases, prostaglandin synthase, 5-lipoxygenase, phosphoinositide 3-kinase, sphingosine kinase and sphingomyelinase. These enzymes and their downstream targets constitute a complex lipid signalling network with multiple nodes of interaction and cross-regulation. Imbalances in this network contribute to the pathogenesis of human disease. Although the function of a particular signalling lipid is traditionally studied in isolation, this review attempts a more integrated overview of the key role of these signalling lipids in inflammation, cancer and metabolic disease, and discusses emerging strategies for therapeutic intervention. <s> BIB002 </s> Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms <s> Introduction <s> Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes? <s> BIB003 </s> Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms <s> Introduction <s> This review describes the use of low-energy collisionally activated dissociation (CAD) with both tandem quadrupole and ion-trap mass spectrometry toward structural characterization of glycerophospholipids (GPLs), including classes of glycerophosphocholine, glycerophosphoethanolamine, glycerophosphoserine, glycerophosphoglycerol glycerophosphoinositol and glycerophosphatidic acid, as well as their lyso-, plasmanyl-, and plasmenylphospholipid subclasses. The mechanisms underlying the fragmentation processes leading to structural characterization of GPLs in various ion forms desorbed by electrospray ionization in the positive-ion and negative-ion modes are also discussed. The tandem mass spectrometric approaches afford the identification of the polar head group, the fatty acid substituents and the location of the radyl groups on the glycerol backbone of all the GPLs. <s> BIB004 </s> Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms <s> Introduction <s> Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPLs) markers of "modified-self" type that are recognized by soluble and cell-associated receptors of innate immunity, including scavenger receptors, natural (germ line-encoded) antibodies, and C-reactive protein, thus directing removal of senescent and apoptotic cells or oxidized lipoproteins. In addition, OxPLs acquire novel biological activities not characteristic of their unoxidized precursors, including the ability to regulate innate and adaptive immune responses. Effects of OxPLs described in vitro and in vivo suggest their potential relevance in different pathologies, including atherosclerosis, acute inflammation, lung injury, and many other conditions. This review summarizes current knowledge on the mechanisms of formation, structures, and biological activities of OxPLs. Furthermore, potential applications of OxPLs as disease biomarkers, as well as experimental therapies targeting OxPLs, are described, providing a broad overview of an emerging class of lipid mediators. <s> BIB005
Biological systems, such as cells, comprise thousands of individual molecular lipid species, called the lipidome of an organism, which can be classified into eight major lipid categories and dozens of lipid classes and subclasses BIB001 . Generally, lipids fulfil three major tasks in cellular systems: Energy storage, structural functions and cellular signaling BIB002 BIB003 . Within the last decade, it became increasingly evident that lipids are not only energy storing bystanders in cellular processes but are a vital part of cellular regulation processes by themselves. As their biological properties strongly depend upon their chemical structure, each molecular lipid species has an individual role in a living system. An imbalance in this system can lead to various pathophysiological conditions such as diabetes, atherosclerosis, liver steatosis, chronic inflammation and also neurodegenerative diseases to name just a few  BIB005 . Improved lipidomic technologies greatly enhance the knowledge about lipid functions at the level of individual species  . Thin layer chromatography (TLC), the classical standard in lipid analysis, is cheap and fast, but it is very limited when it comes to identification issues below the level of lipid classes. Due to its sensitivity and selectivity mass spectrometry (MS) is the method of choice for qualitative and quantitative lipidomic analysis. Although it is not yet possible to detect and quantify all individual lipids in a given cellular system, the aim of lipidomic analysis is to determine as many individual lipids as possible. Compared to biopolymers such as DNA, RNA, carbohydrates or proteins, lipids show much less standardized fragment mass spectra. Each lipid class has its own rules for fragmentation and its specific ionization efficiency BIB004 , which makes development of standardized 'all inclusive' methods a daunting challenge. Depending on the instrumental setup, different layers of information about the molecular structure are to be discovered. Survey approaches sometimes only determine the number of fatty acyl carbons and the number of fatty acyl double bonds, whereas more focused in-depth methods are able to determine structural details down to fatty acid double bond position. Due to the diversity in molecular structures there is no single mass spectrometric approach which could cover detection of the whole lipidome of an organism, but usually it is rather a combination of different experimental platforms. The following article will focus on mass spectrometry instrumentation using electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and MALDI, because these are nowadays the ionization techniques of choice for complex lipids with a molecular weight above 500 Da.