Gertsch Group

Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland

The lipidome - the most glutinous of all omics

The lipidome - the most glutinous of all omics
Jurg Gertsch - Wed Dec 23, 2009 @ 12:47AM
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Some time ago people recognized that lipids are much more than just storage for energy. Although often relatively simple in structure, fatty acid derivatives can exert highly complex biological effects. Today, we know that the generation of bioactive lipids is strictly regulated by different enzymatic systems and that the bioactive lipidome is a dynamic network, which affects many functions, e.g. in the immune system. In order to understand how lipids interact with their receptors and modulate each other the challenge is to simultaneously measure what is going on, which lipids are generated when over time. New technologies employing highly sensitive mass spectrometry (MS) methods are now available which allow for detection of small amounts of lipids. Quantitative analyses of many of these lipids in biological samples or cell cultures are demanding and challenging. E.g. quantification of eicosanoids, which are the signalling molecules derived from arachidonic acid, eicosapentanoic acid or dihomo-gamma-linolenic acid by LC/ESI-MS/MS have yielded detection limits of typically 20 pg/ml or more. Since the lipids have been an intense area of research already in 1960s, the traditional methods in particular for sample preparation and lipid extraction are a valuable source of information also for today's lipidomics platforms. Thus, it is therefore important to go back and read the old papers on lipid biochemistry before inventing everything from scratch. Who e.g. remembers the first study by Poulletier de la Salle of a lipid (cholesterol) isolated from bile stones was as early as 1758. In 1844, the first isolation of linoleic acid ("Leinol") prepared from linseed oil was reproted by Sacc F (Ann 1844, 51, 213). Just after the French patent by Mege-Mouries for the production of "margarine" in 1869 the existence of lipases in plant seeds was noted by Muntz MA (Ann Chem Liebigs 1871, 22, 472). If you don't want to go back as much focus on the year 1979, which was very important for lipid biochemistry. In 1979 Murphy RC et al. elucidated the structure of the slow reacting substance (SRS-A) of anaphylaxis as a new hydroxylated derivative of arachidonic acid which was named leukotriene (PNAS, 1979, 76); Demopoulos CA et al. elucidated the structure of the Platelet-Activating Factor (PAF) as an acetylated alkyl phosphatidylcholine (JBC, 1979, 254); Dyerberg J et al. suggested for the first time a close relationship between platelet aggregation, bleeding time and n-3 polyunsaturated fatty acids (Lancet 1979, 2, 433) and Takai Y et al. described a protein kinase (now protein kinase C) requiring calcium, phosphatidylserine, and diacylglycerol for complete activation (Biochem Biophys Res Comm 1979, 91, 1218). To get an overview of the fundamentals of lipidomics (as it is called today) you may find the webpage cyberlipid.org useful.

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