Ether-linked phosphatidylserine

Lipidomics Gateway (30 December 2009) [doi:10.1038/lipidmaps.2009.38]

Lipidomic analysis reveals unusual glycerophospholipid species in human cells and tissues.

Structure of an ether-linked phosphatidylserine species (18:0e/22:4). The sn-1 position is occupied by a saturated, 18 carbon chain joined by an alkyl ether linkage (yellow box). The sn-2position carries a polyunsaturated 22 carbon chain with the more typical ester linkage (green box).

'Typical' phospholipids consist of fatty acid chains joined to the glycerol backbone by ester linkage. By contrast, ether-linked phospholipids contain either an alkyl ether or vinyl ether bond at the sn-1 position. In mammalian cells, ether-linked lipids are mostly species of phosphatidylcholine (PC) or phosphatidylethanolamine (PE). However, recent studies have identified unusual species, including ether-linked phosphatidylserine (PS), in human cells.

Ether-linked lipids: Plasmalogens

Phospholipids that contain a vinyl ether-linkage are commonly known as plasmalogens. The vinyl part denotes a carbon–carbon double bond on one side of the ether linkage. This structure has consequences for membrane fluidity, and plasmalogen alterations are associated with pathologies including Alzheimer's disease and metastatic cancer 1 b2 . They are reported to protect nervous tissue from the damage associated with the accumulation of very long chain fatty acids 3 , and have antioxidant capability 4 . Although PC and PE plasmalogens comprise roughly 20% of the phospholipids in humans, the only mammalian tissue in which ether-linked PS was identified before 2009 was rat lung 5 .

Not so atypical: Ether-linked PS in humans

In March 2009, Stephen Blanksby and colleagues reported that the human lens contains a number of molecular species of PS ethers 6 . Now, this has been extended by results from the LIPID MAPS project, showing that human macrophages also contain ether-linked PS (among other atypical species) 7 . Both studies illustrate how modern tandem mass spectrometry techniques are increasingly defining cellular lipid content. In the macrophage analysis, ether-linked PS species had very long chain fatty acids in the sn-2 position.

PS: What is it for?

The biological functions of ether-linked PS are unknown. Alongside the other ether-containing phospholipid species, they may contribute to the production of mediators like platelet activating factor, a potent signaling phospholipid. Alternatively, they may be a reservoir for release of very long chain fatty acids upon stimulation, or might have signaling functions of their own.

Emma Leah

References:

  1. Brites, P., Waterham, H. R. & Wanders, R. J. A. Functions of plasmalogens in health and disease.

    Biochim. Biophys. Acta. 1636, 219-231 (2004). doi:10.1016/j.bbalip.2003.12.010

  2. Smith, R. E., Lespi, P., Di Luca, M., Bustos, C., Marra, F.A., de Alaniz, M. J. T. & Marra, C. A. A reliable biomarker derived from plasmalogens to evaluate malignancy and metastatic capacity of human cancers.

    Lipids 43, 79-89 (2008).

  3. Brites, P., Mooyer, P. A. W., el Mrabet, L., Waterham, H. R. & Wanders, R. J. A. Plasmalogens participate in very-long-chain fatty acid-induced pathology.

    Brain 132, 482-492 (2009). doi:10.1093/brain/awn295

  4. Lankalapalli, R., S., Eckelkamp, J. T., Sircar, D., Ford, D. A., Subbaiah, P. V. & Bittman, R. Synthesis and Antioxidant Properties of an Unnatural Plasmalogen Analogue Bearing a trans O-Vinyl Ether Linkage.

    Org. Lett. 11, 2784-2787 (2009). doi:10.1021/ol9009078

  5. Kaneshiro, E. S., Guo, Z., Sul, D., Kallam, K. A., Jayasimhulu, K. & Beach, D. H. Characterizations of Pneumocystis carinii and rat lung lipids: glyceryl ethers and fatty alcohols.

    J. Lipid Res. 39, 1907-1917 (1998).

  6. Deeley, J. M., Thomas, M. C., Truscott, R. J. W., Mitchell, T. W., Blanksby, S. J. Identification of Abundant Alkyl Ether Glycerophospholipids in the Human Lens by Tandem Mass Spectrometry Techniques.

    Anal. Chem. 81, 1920-1930 (2009). doi:10.1021/ac802395d

  7. Ivanova, P. T., Milne, S. B., Brown, H. A Identification of atypical ether-linked glycerophospholipid species in macrophages by mass spectrometry.

    J. Lipid Res. (30 November 2009). doi:10.1194/jlr.D003715

logo NIGMS logo