An analogy of lipids I often use is that they are cellular bricks. They make up the membrane, the wall that separates the inside of the cell from the outside. So, this explanation gets across many of the facets of the lipid quite concisely—there are a variety of sorts, they do not work as individuals, when assembled together they form stable and often lasting structures that are usually much thinner than the spaces they enclose. The epithet ‘cellular bricks’ also suggests that, at least for individuals, they are not that exciting.

I make light of this by tackling the ennui head on, and use the word boring. This gets a half-laugh and gives my interlocutor the chance to say whatever is on their mind, usually either desperately thinking of something to say about anything else, or processing the idea that the word lipid is not synonymous with the word fat.

The trouble with this explanation is that it often leaves me feeling as though I have been pessimistic. There is no proper ‘lift’ at the end to leave things on a nice note.

I am pleased to say that recent work by Kuge et al. [1] and Ersoy et al. [2], has made me change my ideas about how I describe basic lipids—or at least reconsider my stand-up comedy explanation of them. These two reports show that one of the most common lipids in mammals and yeast, phosphatidylcholine, may be rather more exciting as a biological molecule than previously expected.

Kuge et al. [1] show that a particular type of PC, called 1-oleoyl-2-palmitoyl phosphatidylcholine, is concentrated at the tips of growing nerve cells. Ersoy et al. [2] report evidence that an enzyme called PC-transfer protein has a role in insulin signalling. Specifically, PC-transfer protein is involved in a part of the process that goes wrong in type II (obesity and gestational) diabetes.

These two things show a breadth in the functions of PC that are a considerable step forward in our understanding of this lipid.

Delving into it further, I found that there have been hints about this other life of PC for a while. The first evidence appears to be that PC can be a storage lipid. Specifically, it is a pantry for a kind of poly-unsaturated fatty acid called [3,4] that is itself a starting material for prostaglandins in inflammation pathways. Another nudge towards Bethlehem was the observation that it is used to make sphingolipids, lipids that are themselves important signals [5] (you can read more about the importance of sphingolipids here [6]).

The role of PC as a protagonist in the mechanisms behind cancer make it a worthy research interest. However, could one argue that the physical role of PC is more fundamental to our cells?

The first focussed biophysical work on lipids was done on PC in the 1960s. This early work was dominated by Vittorio Luzzatti, who published a paper in 1968 called ‘Polymorphism of Lipids’ [7], and much of it was done on PCs. It was shown that PC has a strong thermodynamic preference for forming bilayer sheets. This correlates almost exactly with how our cellular membranes are constructed. Cellular systems differ in that they have a gentle curvature, that is what allows them to be spheroid objects. In terms of bilayer geometry, this is easily accounted for, just have fewer PC molecules on the inside leaf. Added to which, there are other lipids present anyway. Several of the latter turned out to be lipids that induce curvature in membranes.

These two bodies of work, what we know about the physical behaviour of PC in forming membranes and its biological role in cancer and diabetes, are difficult to compare. It is almost the lipidology equivalent of fatuous questions about whether Newton or Shakespeare is better, or whether a sound exists if a person has not heard it.

The way I prefer to think about it is that the physical and biological importance of PC is like comparing the colour of an orange with its flavour. They are separate things, distinct aesthetic experiences. And one without the other is a bit spooky.


[1] H. Kuge, K. Akahori, K. I. Yagyu. Journal of Biological Chemistry, 2014, 289, 26783. doi: 10.1074/jbc.M114.571075

[2] B. A. Ersoy, A. Tarun, K. D’Aquino, N. J. Hancer, C. Ukomadu, M. F. White, T. Michel, B. D. Manning, D. E. Cohen. Science Signaling, 2013, 6, ra64. doi: 10.1126/scisignal.2004111

[3] V. A. Ziboh, J. T. Lord, Biochemical Journal, 1979, 184, 283.

[4] R. M. Kramer, D. Deykin, Journal of Biological Chemistry, 1983, 258, 13806.

[5] W. D. Marggraf, F. A. Anderer, Hoppe-Seylers Zeitschrift Fur Physiologische Chemie, 1974, 355, 803. doi: 10.1515/bchm2.1974.355.2.803

[6] B. Ogretmen, Y. A. Hannun, Nature Reviews Cancer, 2004, 4, 604. doi:10.1038/nrc1411

[7] V. Luzzati, A. Tardieu, T. Gulik-Krzywicki, Nature, 1968, 217, 1028. doi:10.1038/2171028a0.