Lipidomics Thursday, Dec 15 2011
One of the big questions in biology is how living organisms work. How do we stay alive? Understanding of this over the last two centuries has led to the development of science into the chemistry that sustains life in biological systems. This is what biochemistry is. A recent approach to understanding living systems has been to work out what all the genes are in a given organism. This is all the genome is: all the genes an organism possesses. Knowing what the genes are is useful because it tells us which proteins can be made. These proteins go on to do a variety of things, like speeding up digestion (enzymes), or for making the machinery required for cells to control what passes through their membrane (e.g. ion channels, which you may have read about here). Genes and cataloguing the genome is an important advance in science, but it does not tell us everything.
It is also useful to understand the range of other components present in a system, such as the lipids. Knowing the complete lipid profile, the lipidome, of a system is particularly informative. The word lipidome may seem unfamiliar, but it is the lipid equivalent of the genome in genetics, that is, a catalogue of every lipid in a given species.
Once we know which lipids are present, and how much, we can use published evidence of the individuals’ behaviour to make conclusions about the relationship between what we observe in vivo. Physical evidence from biophysical studies, such as the use of x-rays to determine the topology of the self-assembly in lipid systems , is also used to inform the understanding of these systems. Lipidomics  is a relatively new approach to understanding the lipid fraction of biological systems. In physical terms, it allows us to re-construct the system from the known behaviour of its parts. This is a more fundamental approach that is perhaps superior than simply doing things to lipid systems to find out what happens, such as adding chemicals that disturb the forces that hold lipid systems together. Such chemicals are celled chaotropes [3,4,5].
Lipidomics sounds remarkably easy. We know what we need to do, and there are just a couple of steps to achieve it. We have a problem, however. Isolating these lipid molecules is more difficult than for proteins or DNA. Certainly adding solvents to dissolve the lipids makes sense, but this is awkward if we consider the relationship lipids have with water, and particularly so if they are more like a surfactant (i.e. soap) than a lipid. This has not stopped tenacious lipid chemists from using sophisticated solvent systems to extract lipid fractions from plant, animal, or fungal material , however. But this on its own is not enough. Current lipidomics methodology also uses mass spectrometry to identify the molecules according to their molecular mass. If this is accurate enough, it can be used to determine the number and identity of the atoms present. This in turn is used to pin down the lipids’ identity.
If this approach is applied to a whole organism, such as Saccharomyces cerevisae , the species of yeast used in baking bread and making beer, the results produce a lipidome of that species.
The lipidome tells us about the range of lipids the system is capable of producing, and does produce, which then informs us about the range of physical behaviour of membranes in the system. The most exciting thing about this, in my opinion, is that we might then be able to understand the role of lipids in cell division. How we get from one cell membrane to two is a physical process, but without an understanding of the lipid component we cannot construct a picture of how this happens on a molecular level. Once we do, the understanding of lipids in a system will be at the same level as that of DNA and proteins.
 M. R. Wenk, Nature Reviews, 2005, 594, 594-610. http://staff.washington.edu/mwhiddon/Wenk%20et%20al.pdf
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 C. S. Ejsing, J. L. Sampaio, V. Surendranath, E. Duchoslav, K. Ekroos, R. W. Klemm, K. Simons and A. Shevchenko, Proceedings of the National Academy of Sciences, 2009, 106, 2136-2141. http://www.pnas.org/content/early/2009/01/27/0811700106 .
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