Ether lipid
2268600
221799670
2008-06-26T04:10:44Z
Kingdon
668610
/* Structural */ link to [[archaea]]
[[Image:Ether lipid.png|thumb|Structure of an ether [[phospholipid]]. Note ether at first and second positions.]]
[[Image:plasm.jpg|thumb|[[Plasmalogen]]. Note ether at first position, and ester at second position.]]
[[Image:PAF-platelet activating factor.png|thumb|[[Platelet-activating factor]]. Note ether at first position, and [[acetyl]] group at second position.]]
'''Ether lipids''' are [[lipid]]s in which one or more of the [[carbon]] [[atom]]s on [[glycerol]] is bonded to an [[alkyl]] chain via an [[ether]] linkage, as opposed to the usual [[ester]] linkage.
==Types==
Ether lipids are called [[plasmalogen]]s (1-O-1'-alkenyl-2-acylglycerophospholipids) if these are [[glycerol]]-containing [[phospholipid]]s with an unsaturated ''O''-(1-alkenyl) ([[vinyl]] [[ether]]) group at the first position on the glycerol chain.
[[Platelet-activating factor]] is an ether lipid which has an [[acetyl]] group instead of an [[acyl chain]] at the second position (SN-2).
==Biosynthesis==
The formation of the ether bond in mammals requires two enzymes, dihydoxyacetonephosphate acyltransferase (DHAPAT) and alkyldihydroxyacetonephosphate synthase (ADAPS), that reside in the [[peroxisome]]. <ref name="pmid8685243">{{cite journal |author=Hajra AK |title=Glycerolipid biosynthesis in peroxisomes (microbodies) |journal=Prog. Lipid Res. |volume=34 |issue=4 |pages=343–64 |year=1995 |pmid=8685243 |doi=}}</ref> Accordingly, peroxisomal defects often lead to impairment of ether-lipid production.
==Functions==
===Structural===
Plasmalogens as well as some 1-O-alkyl lipids are ubiquitous and sometimes major parts of the [[cell membrane]]s in [[mammal]]s and [[anaerobic]] [[bacteria]].<ref>{{cite journal |author=Paltauf F |title=Ether lipids in biomembranes |journal=Chem Phys Lipids |volume=74 |issue=2 |pages=101–39 |year=1994 |pmid=7859340 |doi=10.1016/0009-3084(94)90054-X}}</ref> In [[archaea]], ether lipids are the major polar lipids in the cell envelope and their abundance is one of the major characteristics that separate this group of [[prokaryote]]s from the [[bacteria]]. In these cells, diphytanylglycerolipids or bipolar macrocyclic tetraethers can form [[covalent]]ly linked 'bilayers'.<ref>{{cite journal |author=Koga Y, Morii H |title=Recent advances in structural research on ether lipids from archaea including comparative and physiological aspects |url=http://www.jstage.jst.go.jp/article/bbb/69/11/69_2019/_article |journal=Biosci Biotechnol Biochem |volume=69 |issue=11 |pages=2019–34 |year=2005 |pmid=16306681 |doi=10.1271/bbb.69.2019}}</ref>
===Second messenger===
Differences between the [[catabolism]] of ether glycerophospholipids by specific [[phospholipase]]s [[enzyme]]s might be involved in the generation of lipid [[second messenger system]]s such as [[prostaglandin]]s and [[arachidonic acid]] that are important in signal transduction.<ref>{{cite journal |author=Spector A, Yorek M |title=Membrane lipid composition and cellular function |url=http://www.jlr.org/cgi/reprint/26/9/1015 |journal=J Lipid Res |volume=26 |issue=9 |pages=1015–35 |year=1985 |pmid=3906008}}</ref> 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]].<ref>{{cite journal |author=Demopoulos C, Pinckard R, Hanahan D |title=Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators) |url=http://www.jbc.org/cgi/reprint/254/19/9355 |journal=J Biol Chem |volume=254 |issue=19 |pages=9355–8 |year=1979 |pmid=489536}}</ref>
===Antioxidant===
Another possible function of the plasmalogen ether lipids is as [[antioxidant]]s, as protective effects against [[oxidative stress]] have been demonstrated in [[cell culture]] and these lipids might therefore play a role in serum [[lipoprotein]] metabolism.<ref>{{cite journal |author=Brosche T, Platt D |title=The biological significance of plasmalogens in defense against oxidative damage |journal=Exp Gerontol |volume=33 |issue=5 |pages=363–9 |year=1998 |pmid=9762517 |doi=10.1016/S0531-5565(98)00014-X}}</ref> This antioxidant activity comes from the enol ether double bond being targeted by a variety of [[reactive oxygen species]].<ref>{{cite journal |author=Engelmann B |title=Plasmalogens: targets for oxidants and major lipophilic antioxidants |journal=Biochem Soc Trans |volume=32 |issue=Pt 1 |pages=147–50 |year=2004 |pmid=14748736 |doi=10.1042/BST0320147}}</ref>
==Synthetic ether lipid analogs==
Synthetic ether lipid analogs have [[chemotherapy|cytostatic and cytotoxic]] properties, probably by disrupting membrane structure and acting as [[enzyme inhibitor|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.<ref>{{cite journal |author=Lux H, Heise N, Klenner T, Hart D, Opperdoes F |title=Ether--lipid (alkyl-phospholipid) metabolism and the mechanism of action of ether--lipid analogues in Leishmania |journal=Mol Biochem Parasitol |volume=111 |issue=1 |pages=1–14 |year=2000 |pmid=11087912 |doi=10.1016/S0166-6851(00)00278-4}}</ref>
==References==
{{reflist}}
==External links==
* {{MeshName|Ether+phospholipids}}
{{orgchem-stub}}
{{biochem-stub}}
{{Phospholipids}}