Phospholipids ether

Plasmalogens and platelet-activating factor (PAF) are ether phospholipids formed from dihydroxyacetone phosphate. 

This chapter surveys the neurochemistry of lipid messengers, as well as the mechanisms by which bioactive lipids accumulate upon stimulation in response to injury, cerebral ischemia, seizures, neurotrauma or neurodegen-erative diseases, and their significance in pathophysiology. Emphasis is placed on three groups of bioactive lipids AA and its metabolites, known collectively as eicosanoids PAF, a highly potent ether phospholipid and the newly identified DHA-derived mediator, neuroprotectin Dl. 

Alkyl-dihydroxy phosphate synthase and dihydroxy-phosphate acyltransferase deficiencies. Both these disorders lead to severe deficiencies of ether phospholipids and lead to syndromes that are similar to RCDP, and point to the key physiological roles of ether phospholipids. 

Kornecki E, Lenox RH, Hardwick DH, et al. Interactions of the alkyl-ether-phospholipid, platelet activating factor (PAF) with platelets, neural cells, and the psychotropic drugs triazolobenzodiazepines. AdvExp Med Biol 1987 221 477-488. 

Ether phospholipids, analogous to the ether lipids described in Section 2, are also widely distributed. Tire alkenyl ether analogs of phosphatidylcholine (Fig. 8-2) are called plasmalogens.17 In neutrophils the 1-O-alkyl ethers contain the major share of the cell s arachidonic acid, which is esterified in the 2 position.1819... 

PAF has been identified as the following simple ether phospholipid 3 d... 

Glycolipids are important constituents of the plasma membranes, of the endoplasmic reticulum, and of chloroplasts. The cerebrosides and their sulfate esters, the sulfatides, are especially abundant in myelin. In plant membranes, the predominant lipids are the galactosyl diglycerides.29 74 The previously described ether phospholipids (archaebacteria), ceramide arnino-ethylphosphonate (invertebrates), and sulfolipid (chloroplasts) are also important membrane components. 

Glycerophospholipids contain a glycerol skeleton to which two fatty acids are esterified saturated fatty acids occupy mostly sn-position 1, whereas unsaturated fatty acids are mainly present on sn-position 2. The third hydroxyl is linked to a phosphate group to which an organic base is mostly esterified (Fig. 1). The most important components of soybean lecithin are phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Phosphatidic acid (PA) may become important due to the presence of phospholipase D this enzyme slowly converts PC into PA in vegetable lecithins. Phosphatidylserine (PS), phosphatidylglycerol (PG), and lyso-phosphatidylcholine (LPC) are known as minor components lysophospholipids contain only one acyl group per molecule. Besides, ether phospholipids occur in which one or both fatty acyl... 

Most phospholipids are essentially disubstituted phosphates (Figure 1.27). They may be initially classified as phosphatidyl compounds, plasmalogens, ether phospholipids and sphingomyelins depending on the nature of the Ri group attached to the phosphate residue (Table 1.6). 

The a-phosphatidyl lipids are further subdivided according to the nature of their R2 residues (Table 1.7). The R2 groups of plasmalogens and ether phospholipids are similar to the R2 groups of the phosphatidyl lipids, whilst the sphingomyelins have a choline residue. 

The results of several investigations on the mechanism of action of tumoricidal ether phospholipids support the assumption that biochemical and physicochemical properties of the cell membrane are involved. 

The fluidization and increase in permeability of tumor cell membranes has been reported [43, 44], as well as changes in cellular lipid synthesis during ether phospholipid-induced cytolysis [45]. Direct evidence was found by Diomede et al. [46] and Principe et al. [47] for the importance of the lipid composition of membranes for the sensitivity to antineoplastic ether phospholipids. These authors studied the influence of tumor cell membrane cholesterol content on the sensitivity of leukemic cells [46] and cells derived from three human carcinomas [47] with different rates of cell... 

There are also differences in the composition of the phospholipids in human platelets. These cells contain a little over twice as much phosphatidylcholine as sphingomyelin. Another dramatic difference is noted in the ether phospholipid content in the human platelets, where there is approximately 37% vinyl ether-containing components in the ethanolamine fraction whereas there only are 10% or less in the other phosphoglyceride species. The vinyl ether linkage has not been detected in the sphingolipids of these cells. 

Different fatty chain components of alkenylacyl, alkylacyl and di-acylphospholipids in rabbit aveolar macrophages high amounts of arachidonic acid in ether phospholipids, Lipids 18, 125-129. 

Balazy, M., Braquet, P., and Bazan, N. G. (1991) Determination of platelet-activating factor and alkyl-ether phospholipids by gas chromatography-mass spectrometry via direct derivatization, Anal. Biochem. 196, 1-10. 

Gajate, C., Santos-Beneit, A., Modolell, M., and Mollinedo, E, 1998, Involvement of c-Jun NH2-terminal kinase activation and c-Jun in the induction of apoptosis by the ether phospholipid l-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine. Mol Pharmacol, 53 602-612... 

Plasmalogens and Other Ether Phospholipids Are Synthesized from Dihydroxyaeetone Phosphate... 

Platelet-activating factor (PAF) is an ether phospholipid implicated in a number of allergic and inflammatory responses. 

Figure 26.2. Synthesis of an Ether Phospholipid. Steps in the synthesis include (1) acylation of dihydroxyacetone phosphate by acyl CoA, (2) exchange of an alcohol for the carboxylic acid, (3) reduction by NADPH, (4) acylation by a second acyl CoA, (5) hydrolysis of the phosphate ester, and (6) transfer of a phosphocholine moiety.

In addition to the previously mentioned phytanyl ether phospholipids, methanogens contain diphytanyl tetraether lipids that are both glycerophospholipids and glycolipids. 

A further degree of complexity is provided by the fact that the fatty acid at the Snl position may be attached by either an acyl group or an alkyl group. The alkyl series are known as ether phospholipids and have different properties from the acyl phospholipids. Although some enzymes can act equally well on acyl and on ether phospholipids, most are specific for one or the other. The outlines of acyl phospholipid metabolism, which are given later, can almost all be duplicated by an equivalent set of either phospholipid reactions. 

The synthesis of phospholipids and analogues, mainly by well-established methods, continues to be actively pursued. A new, stereospecific route to functionalised ether phospholipids, e.g. (54) and (55), as analogues of l-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) and modulation phospholipids, has been reported. The route uses (/ )-glycidyl tosylate (56) as the chiral precursor... 

Purdon, A. D. Smith, J. B. (1985). Turnover of arachidonic acid in the major diacyl and ether phospholipids of human platelets. J. Biol. Chem. 260, 12700-12704. 

Ether phospholipids are important cell membrane biomolecules involved in signal transduction, neuroplasticity, tumor growth, and membrane fluidity and trafficking." Alkyidihydroxyacetonephosphate synthase (ADPS) is an FAD-containing protein that catalyzes the formation of the ether bond of ether phospholi-pids." " Alkyidihydroxyacetonephosphate (alkyl-DHAP) is formed by exchange of the acyl moiety of acyl-DHAP with a fatty alcohol (Equation (20)). 

Insights from genetic diseases with impaired ether phospholipid... 

Tumor ether phospholipids and anti-tumor ether phospholipids. 274... 

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