Lipids are important small-molecule metabolites that have roles in a wide variety of physiological processes.
Deregulation of lipid metabolism leads to onset of pathology, including many forms of cancer, diabetes and neurodegenerative diseases.
Genetics, cell biology and biochemistry have fundamentally advanced our understanding of the biology of lipids in recent years.
Novel methodologies for the biochemical analysis of lipids and their effectors will substantially further the field of lipid research, in particular at systems-level scale (lipidomics) approaches.
These technologies are valuable tools at various stages of the drug development process, most importantly in target discovery and biomarker development.
One of the major advantages of biochemical lipidomics, which aims at measuring lipid metabolites and their effectors, is that it might directly lead to the identification pathways of lipid action or lipid metabolism.
The crucial role of lipids in cell, tissue and organ physiology is demonstrated by a large number of genetic studies and by many human diseases that involve the disruption of lipid metabolic enzymes and pathways. Examples of such diseases include cancer, diabetes, as well as neurodegenerative and infectious diseases. So far, the explosion of information in the fields of genomics and proteomics has not been matched by a corresponding advancement of knowledge in the field of lipids, which is largely due to the complexity of lipids and the lack of powerful tools for their analysis. Novel analytical approaches — in particular, liquid chromatography and mass spectrometry — for systems-level analysis of lipids and their interacting partners (lipidomics) now make this field a promising area of biomedical research, with a variety of applications in drug and biomarker development.
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I would like to thank all members of our group and those of the labs of G. Di Paolo, M. Kemeny and U.-A. Boelsterli, as well as the external reviewers for their constructive comments. Work in our laboratory is supported by research grants from the National University of Singapore, the National Medical Research Council of Singapore and the Novartis Institutes for Tropical Research.
The author declares no competing financial interests.
Systems-level analysis and characterization of lipids and their interacting moieties.
- SYSTEMS BIOLOGY
A discipline that aims at deciphering relationships between different parts of a biological system (for example, a metabolic chain, cell or tissue) with the goal of understanding (and predicting) the behaviour of the system as a whole.
- INTERFACIAL CATALYSIS
Enzymatic catalysis at an interface, such as the surface of a biological membrane.
- PH DOMAIN
Pleckstrin homology domain. A widespread and functionally diverse protein fold that mediates intermolecular interactions, most notably with phosphoinositides.
- LIPID MEDIATOR
A lipid molecule that mediates a biological response. Lipid mediators form distinct classes of bioactive molecules rather than mere intermediates of lipid metabolism (for example, arachidonic acid metabolites (eicosanoids) or platelet-activating factor).
A chemical that transmits information from a neuron to a neighbouring cell.
Complex glycosphingolipids that carry three or more sugars on a ceramide backbone. Some of the sugars include sialic acid and N-acetylneuranimic acid.
- TANDEM MASS SPECTROMETRY
Methods that include at least two stages of mass analysis, in conjunction with a dissociation process.
- THIN-LAYER CHROMATOGRAPHY
Commonly used chromatographic method. Analyte is separated by chromatographic material, which is immobilized as a thin layer on a solid support such a glass plate.
Small (nm–μm) spherical particles that are composed of lipid bilayers. Liposomes are used in biophysical and biochemical binding studies, as carriers in drug delivery and cosmetic formulations.
An endocannabinoid arachidonic acid metabolite (arachidonylethanolamine).
A discipline that aims at the quantitative and comprehensive analysis of all metabolites. Although the term 'metabolomic' is used here no side is taken with respect to the distinction between the two terms.
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