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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 acetyl group at second position.

In an organic chemistry general sense, an ether lipid implies an ether bridge between an alkyl group (a lipid) and an unspecified alkyl or aryl group, not necessarily glycerol. In a biochemical sense, an ether lipid usually implies glycerophospholipids of various type, also called phospholipids, in which the sn-1 position of the glycerol backbone has a lipid attached by an ether bond. This is in contrast to the more common glycerophospholipids in which the glycerol backbone sn-1 and sn-2 positions have acyl chains attached by ester bonds.[1] Ether lipid may also refer to alkylglycerols, such as chimyl, batyl, and selachyl alcohols, with a ether-bound lipid on position sn-1, and the other two positions on the glycerol backbone unoccupied.[2]

Contents

TypesEdit

There are two types of ether lipids, plasmanyl- and plasmenyl-phospholipids. Plasmanyl-phospholipids have an ether bond in position sn-1 to an alkyl group. Plasmenyl-phospholipids have an ether bond in position sn-1 to an alkenyl group. The latter type is called plasmalogens.[3]

Platelet-activating factor (PAF) is an ether lipid which has an acetyl group instead of an acyl chain at the second position (SN-2).

BiosynthesisEdit

The formation of the ether bond in mammals requires two enzymes, dihydroxyacetonephosphate acyltransferase (DHAPAT) and alkyldihydroxyacetonephosphate synthase (ADAPS), that reside in the peroxisome.[4] Accordingly, peroxisomal defects often lead to impairment of ether-lipid production.

Monoalkylglycerol ethers (MAGEs) are also generated from 2-acetyl MAGEs (precursors of PAF) by KIAA1363.

FunctionsEdit

StructuralEdit

Plasmalogens as well as some 1-O-alkyl lipids are ubiquitous and sometimes major parts of the cell membranes in mammals and anaerobic bacteria.[5] 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 prokaryotes from the bacteria. In these cells, diphytanylglycerolipids or bipolar macrocyclic tetraethers can form covalently linked 'bilayers'.[6]

Second messengerEdit

Differences between the catabolism of ether glycerophospholipids by specific phospholipases enzymes might be involved in the generation of lipid second messenger systems such as prostaglandins and arachidonic acid that are important in signal transduction.[7] 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.[8]

AntioxidantEdit

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.[9] This antioxidant activity comes from the enol ether double bond being targeted by a variety of reactive oxygen species.[10]

Synthetic ether lipid analogsEdit

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.[11]

See alsoEdit

ReferencesEdit

  1. ^ https://link.springer.com/article/10.1007/s13238-017-0423-5
  2. ^ http://www.lipidhome.co.uk/lipids/complex/ethers/index.htm
  3. ^ www.sciencedirect.com/science/book/9780124105270
  4. ^ Hajra AK (1995). "Glycerolipid biosynthesis in peroxisomes (microbodies)". Prog. Lipid Res. 34 (4): 343–64. PMID 8685243. doi:10.1016/0163-7827(95)00013-5. 
  5. ^ Paltauf F (1994). "Ether lipids in biomembranes". Chem Phys Lipids. 74 (2): 101–39. PMID 7859340. doi:10.1016/0009-3084(94)90054-X. 
  6. ^ Koga Y, Morii H (2005). "Recent advances in structural research on ether lipids from archaea including comparative and physiological aspects". Biosci Biotechnol Biochem. 69 (11): 2019–34. PMID 16306681. doi:10.1271/bbb.69.2019. 
  7. ^ Spector A, Yorek M (1 September 1985). "Membrane lipid composition and cellular function". J Lipid Res. 26 (9): 1015–35. PMID 3906008. 
  8. ^ Demopoulos C, Pinckard R, Hanahan D (10 October 1979). "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)". J Biol Chem. 254 (19): 9355–8. PMID 489536. 
  9. ^ Brosche T, Platt D (1998). "The biological significance of plasmalogens in defense against oxidative damage". Exp Gerontol. 33 (5): 363–9. PMID 9762517. doi:10.1016/S0531-5565(98)00014-X. 
  10. ^ Engelmann B (2004). "Plasmalogens: targets for oxidants and major lipophilic antioxidants". Biochem Soc Trans. 32 (Pt 1): 147–50. PMID 14748736. doi:10.1042/BST0320147. 
  11. ^ Lux H, Heise N, Klenner T, Hart D, Opperdoes F (2000). "Ether--lipid (alkyl-phospholipid) metabolism and the mechanism of action of ether--lipid analogues in Leishmania". Mol Biochem Parasitol. 111 (1): 1–14. PMID 11087912. doi:10.1016/S0166-6851(00)00278-4. 

External linksEdit