thumb|Structure of an ether [[phospholipid. Note ether at first and second positions.]]
thumb|[[Plasmalogen. Note ether at first position, and ester at second position.]]
thumb|[[Platelet-activating factor. Note ether at first position, and acyl group at second position.]]
In biochemistry, an ether lipid refers to any lipid in which the lipid "tail" group is attached to the glycerol backbone via an ether bond at any position. In contrast, conventional glycerophospholipids and triglycerides are triesters. Structural types include:
- Ether phospholipids: phospholipids are known to have ether-linked "tails" instead of the usual ester linkage.
Based on whether the sn-1 lipid is unsaturated next to the ether linkage, they can be further divided into alkenyl-acylphospholipids ("plasmenylphospholipid", 1-0-alk-1’-enyl-2-acyl-sn-glycerol) and alkyl-acylphospholipids ("plasmanylphospholipid"). This class of lipids have important roles in human cell signaling and structure.</p>
- Ether on sn-2 and sn-3: this class with flipped chirality on the phosphate connection is called an "archaeal ether lipid". With few (if any) exceptions, it is only found among archaea. The part excluding the phosphate group is known as archaeol.
- Ether analogues of triglycerides: 1-alkyldiacyl-sn-glycerols (alkyldiacylglycerols) are found in significant proportions in marine animals. Accordingly, peroxisomal defects often lead to impairment of ether-lipid production.
The conversion of an ordinary saturated ether lipid into a plaminogen is achieved by plasmanylethanolamine desaturase (PEDS1), which catalyzes an aerobic oxidation in the endoplamic reticulum.
Monoalkylglycerol ethers (MAGEs) are also generated from 2-acetyl MAGEs (precursors of platelet-activating factor) by KIAA1363.
Functions
Structural
Plasmalogens as well as some 1-O-alkyl lipids are ubiquitous and sometimes major parts of the cell membranes in mammals. The glycosylphosphatidylinositol anchor of mammalian proteins generally consist of an 1-O-alkyl lipid. Ether lipids can also act directly in cell signaling, as the platelet-activating factor is an ether lipid signaling molecule that is involved in leukocyte function in the mammalian immune system.
Antioxidant
Another possible function of the plasmalogen ether lipids is as antioxidants, as protective effects against oxidative stress have been demonstrated in cell culture and these lipids might therefore play a role in serum lipoprotein metabolism. This antioxidant activity comes from the enol ether double bond being targeted by a variety of reactive oxygen species.
Synthetic ether lipid analogs
Synthetic ether lipid analogs have cytostatic and cytotoxic properties, probably by disrupting membrane structure and acting as inhibitors of enzymes within signal transmission pathways, such as protein kinase C and phospholipase C.
A toxic ether lipid analogue miltefosine has recently been introduced as an oral treatment for the tropical disease leishmaniasis, which is caused by leishmania, a protozoal parasite with a particularly high ether lipid content in its membranes.
In archaea
The cell membrane of archaea consist mostly of ether phospholipids. These lipids have a flipped chirality compared to bacterial and eukaryotic membranes, a conundrum known as the "lipid divide". The "tail" groups are also not simply n-alkyl groups, but highly methylated chains made up of saturated isoprenoid units (e.g. phytanyl).
Among different groups of archaea, diverse modifications on the basic archaeol backbone have emerged.
- The two (usually C<sub>20</sub>) tails can be linked together, forming a macrocyclic lipid.
See also
- Membrane lipid
- Glycerol dialkyl glycerol tetraether