Structure of an ether phospholipid. Note ether at first and second positions.Plasmalogen. Note ether at first position, and ester at second position.Platelet-activating factor. Note ether at first position, and acyl group at second position.
Ether phospholipids: phospholipids are known to have ether-linked "tails" instead of the usual ester linkage.[1]
Ether on sn-1, ester on sn-2: "ether lipids" in the context of bacteria and eukaryotes refer to this class of lipids. Compared to the usual 1,2-diacyl-sn-glycerol (DAG), the sn-1 linkage is replaced with an ester bond.[1][2][3]
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.[4]
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 phoshphate group is known as archaeol.[5][6]
Ether analogues of triglycerides: 1-alkyldiacyl-sn-glycerols (alkyldiacylglycerols) are found in significant proportions in marine animals.[5]
Other ether lipids: a number of other lipids not belonging to any of the classes above contain the ether linkage. For example, seminolipid, a vital part of the testes and sperm cells, has a ether linkage.[1]
The term "plasmalogen" can refer to any ether lipid with a vinyl ether linkage, i.e. ones with a carbon-carbon double bond next to the ether linkage. Without specification it generally refers to alkenyl-acylphospholipids, but "neutral plasmalogens" (alkenyldiacylglycerols) and "diplasmalogens" (dialkenylphospholipids) also exist.[1] The prototypical plasmalogen is platelet-activating factor.[7]
Plasmalogens as well as some 1-O-alkyl lipids are ubiquitous and sometimes major parts of the cell membranesinmammals.[9] The glycosylphosphatidylinositol anchor of mammalian proteins generally consist of an 1-O-alkyl lipid.[1]
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.[12] This antioxidant activity comes from the enol ether double bond being targeted by a variety of reactive oxygen species.[13]
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.[14]
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).[15]
Among different groups of archaea, diverse modifications on the basic archaeol backbone have emerged.
The two tails can be linked together, forming a macrocyclic lipid.[15]
Bipolar macrocyclic tetraether lipids (caldarchaeol), with two glycerol units connected by two C40 "tail" chains, form covalently linked 'bilayers'.[16][15]
Some such covelant bilayers feature crosslinks between the two chains, giving an H-shaped molecule.[15]
Crenarchaeol is a tetraether backbone with cyclopentane and cyclohexane rings on the cross-linked "tail"s.[15]
Some lipids replace the glycerol backbone with four-carbon polyols (tetriols).[15]
Ether phospholipids are major parts of the cell membrane in anaerobic bacteria.[1] These lipids can be variously 1-O-alkyl, 2-O-alkyl, or 1,2-O-dialkyl. Some groups have, like archaea, evolved tetraether lipids.[17]
^Engelmann B (February 2004). "Plasmalogens: targets for oxidants and major lipophilic antioxidants". Biochemical Society Transactions. 32 (Pt 1): 147–50. doi:10.1042/BST0320147. PMID14748736.
^Lux H, Heise N, Klenner T, Hart D, Opperdoes FR (November 2000). "Ether--lipid (alkyl-phospholipid) metabolism and the mechanism of action of ether--lipid analogues in Leishmania". Molecular and Biochemical Parasitology. 111 (1): 1–14. doi:10.1016/S0166-6851(00)00278-4. PMID11087912.
