Phosphatidylcholine

Lipidomics Gateway (23 September 2009) [doi:10.1038/lipidmaps.2009.27]

As the major phospholipid component of mammalian cell membranes, phosphatidylcholine species underpin membrane transport and phospholipid signaling pathways.

Model of phosphatidylcholine (PC). Visit diacylglycerophospholipids in the LIPID MAPS structure database for more molecular information.

If membrane proteins are icebergs, and microdomains are rafts, then the sea in which they float consists largely of phosphatidylcholine (PC) molecules. Accounting for more than 50% of mammalian cell membrane phospholipids, and more than 30% of total cellular lipid content, PCs are actually a diverse group of related species 1 2 .

Composition: Being PC

The invariant portion of PC is a glycerol phosphate backbone with a choline headgroup attached at the sn-3 position. Two fatty acid moieties are attached at positions sn-1 and sn-2, and it is the nature of these that confers variation; they differ in length, and in the number of double bonds. The systematic names and abbreviations of each species describe which acyl chains are attached: for example, PC(16:0/18:0), or 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine, has a 16-carbon saturated chain at position 1, and an 18-carbon saturated chain at position 2.

Membrane dynamics: Cylinders, cones and curves

The acyl chains of PC self-associate to form a planar bilayer with a hydrophobic interior, leaving the polar head groups to border the aqueous phase on the outside. Unsaturated, kinked acyl chains confer fluidity on the membrane. With its cylindrical shape, PC does not induce curvature but it can be metabolized into other phospholipids that do. These either have bulkier acyl chains than headgroup or vice versa, making them cone or inverted-cone shaped. The exchange of phospholipids between bilayer leaflets is selectively controlled by proteins, so an increased concentration of cones on one side and inverted cones on the other can be established to induce curvature. Metabolism of PC participates in membrane transport and fusion processes that require curvature, and disruption of the ratio of PC to other phospholipids is associated with altered membrane permeability and disease 2 3 . How membrane curvature is controlled, and how it in turn controls the localization of membrane components, is incompletely understood. However, new work highlighted this month in “Membrane curvature: Bending begets binding” suggests that membrane curvature intrinsically controls the location of hydrophobically-anchored proteins 4 .

Signaling: Active metabolites

Membrane dynamics influence cell signaling, by controlling the localization and interactions of membrane proteins, but PC metabolism also feeds directly into signaling pathways. Active metabolites include phosphatidic acid, which is generated from PC by phospholipase D-mediated cleavage 5 . Other second messengers are produced by further metabolism, activating numerous signaling cascades.

New methods: PC secrets unveiled

The same advances in mass spectrometry that paved the way for the birth of lipidomics 6 7 are, naturally, also facilitating the study of PC. Quantitative analyses of different phospholipids, and even of different PC species, are becoming both possible and increasingly sensitive 1 . Furthermore, our highlight this month “Choline phospholipids: Now you see them” features a new technique for in vivo imaging of PC molecules 8 . The remaining mysteries of PC's intracellular behavior and the relative properties of each distinct species appear ever more solvable.

References:

  1. Ekroos, K., Ejsing, C. S., Bahr, U., Karas, M., Simons, K. & Shevchenko, A. Charting molecular composition of phosphatidylcholines by fatty acid scanning and ion trap MS3 fragmentation.

    J. Lipid Res. 44, 2181-2192 (2003). doi:10.1194/jlr.D300020-JLR200

  2. van Meer, G., Voelker, D. R. & Feigenson, G. W. Membrane lipids: where they are and how they behave.

    Nat. Rev. Mol. Cell Bio. 9, 112-124 (2008). doi:10.1038/nrm2330

  3. Li, Z. & Vance, D. E. Phosphatidylcholine and choline homeostasis.

    J. Lipid Res. 49, 1187-1194 (2008). doi:10.1194/JLR.r700019-jlr200

  4. Hatzakis, N. S., Bhatia, V. K., Larsen, J., Madsen, K. L., Bolinger, P-Y., Kunding, A. H., Castillo, J., Gether, U., Hedegård, P. & Stamou, D. How curved membranes recruit amphipathic helices and protein anchoring motifs.

    Nat. Chem. Bio. (13 September 2009). doi:10.1038/nchembio.213

  5. McDermott, M., Wakelam, M. J. O. & Morris, A.J. Phospholipase D.

    Biochem. Cell Biol. 82, 225-253 (2004). doi:10.1139/o03-079

  6. Dennis, E.A. Lipidomics joins the omics evolution.

    Proc. Natl Acad. Sci. USA 106, 2089-2090 (2009). doi:10.1073/pnas.0812636106

  7. Brown, A.H. & Murphy, R. C. Working towards an exegesis for lipids in biology.

    Nat. Chem. Bio. 5, 602-606 (2009). doi:10.1038/nchembio0909-602

  8. Jao, C. Y., Roth, M., Welti, R. & Salic, A. Metabolic labeling and direct imaging of choline phospholipids in vivo.

    Proc. Natl Acad. Sci. USA 106, 15332-15337 (2009). doi:10.1073/pnas.0907864106