Lipids ether

Milk fat contains small amounts of ether lipids. Synthetic ether lipids at low concentrations are potent anti-neoplastic agents. Cell culture studies showed that they inhibited cell growth, induced differentiation, promoted apoptosis and showed anti-metastatic activity. In human chemoprevention trials ether lipids have been administered parenterally. Although the ether bond is preserved when these lipids are delivered orally, no cancer chemoprevention studies have utilized dietary ether lipids (Parodi, 2004). 

Evidence of a role for dietary cholesterol in carcinogenesis, using animal models, is contradictory. This may result, in part, from contamination of 

Cornpounds (67)-(69) termed botryococcoid ethers were isolated from external lipids and purified by TLC and HPLC. The El and 

The position of the functions of the two C27 chains was determined both from the major spectral fragments observed in the EIMS as shown in Fig. 14, and by identification of n-Ci5 and n-C diacids in ozonolysis by-products. All these results led to establishment of structure (67) for the alkatrienyl-alkadienyl ether. 

The alkyl-alkadienyl ethers (68) and (69) were isolated as a white solid mixture these minor compounds from the Overjuyo and Coat ar Herno strains (together amounting to 1.1% of dry biomass) were identified as C51H100O2 C53H104O2 respectively. C-NMR and MS spectra 

Despite the lack of direct evidence, the most likely mechanism for the formation of botryococcoid ether (67) is the coupling of two monoepoxides (70) and (71) derived from the trienic hydrocarbon (4) (Fig. 15). 

El and CI(NH3) mass spectra established that (72), (73) and (74) correspond to homologous series of compounds of high molecular weight differing by 28 uma 802 to 914 for (72), 1066 to 1346 for (73) and 1248-1332 for (74). Since all MS techniques tested failed to produce the molecular peak, the botryalalkenyl ethers (75) were examined by size exclusion HPLC on an ultraStyragel column using THE as eluent the retention volume was consistent with a M of 1650 140 daltons. 

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Figure 24-4. Biosynthesis of ether lipids, including plasmalogens, and platelet-activating factor (PAF). In the de novo pathway for PAF synthesis, acetyl-CoA is incorporated at stage, avoiding the last two steps in the pathway shown here.

H.K. Mangold and F. Paltauf, Ether Lipids (Academic Press, New York, 1983). 

R. Saunders, R. Anderson, D. Handley, W. Houlihan, M. Lee, J. Tomesch and C. Winslow, Second International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Gatlinburg, TN, October 26-29 (1986) Abstr. p. 33. 

In contrast, LysoPC could not reverse the cytostatic effect of ET-18-OCH3 (Boggs etal, 1998). Likewise overexpression ofCT could prevent the apoptosis induced by ET-I8-OCH3, but could not restore proliferation of the HeLa cells in the presence of this ether lipid (Baburina and Jackowski, 1998). 

Jensen SS, Andresen TL, Davidsen J, et al. Secretory phospholipase A2 as a tumor-specific trigger for targeted delivery of a novel class of liposomal prodrug anticancer ether lipids. Mol Cancer Ther 2004 3 1451-1458. 

Finally, besides conventional liposomes that are made from natural (e.g., egg yolk and soybean) or synthetic phospholipids, novel liposomes called archaeosomes that are prepared from the polar ether lipids extracted from various archaeobacteria proved also interesting for the design of vaccines as peptide antigen carriers (71) and as powerful self-adjuvanting vaccine delivery vesicles that promote both humoral and cell-mediated immunity (72). Related to this, one can mention that pseudopeptides, which are less prone to proteolysis when conjugated to liposomes, were also competent in triggering a humoral immune response (73). 

DPIEL D-3-deoxy-phosphatidyl-fnyo-inositol ether lipid... 

Civoli F, Daniel LW (1998) Quaternary ammonium analogs of ether lipids inhibit the activation of protein kinase C and the growth of human leukemia cell lines. Cancer Chemother Pharmacol 42 319-326... 

Noseda A, Berens ME, White JG, Modest EJ (1988) In vitro antiproliferative activity of combinations of ether lipid analogues and DNA interactive agents against human tumor cells. Cancer Res 48 1788-1791 Obeid LM, Linardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259 1769-1771 O Brian CA, Vogel, VG, Singletary SE, Ward NE (1989a) Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue. Cancer Res 49 3215-3217... 

Workman P (1991) Antitumor ether lipids endocytosis as a determinant of cellular sensitivity. Cancer Cells 3 315-317... 

Increased plasmalogen levels have not been observed. Erroneously low red cell levels can be encountered when the transmethylation process has not been completed. Breaking the ether lipid bond of the plasmalogens requires more energy than hydrolysis of the fatty acid esters. Evaluation of the plasmalogen levels should not be done after a blood transfusion. Donor erythrocytes will be present for up to 120 days following a transfusion. 

Berggren, M.L Gallegos, A. Dressier, L.A. Modest, E.J. Powis, G. Inhibition of the signalling enzyme phosphatidylinositol-3-kinase by antitumor ether lipid analogs. Cancer Res., 53, 4297-4302 (1993)... 

Some animal tissues and some unicellular organisms are rich in ether lipids, in which one of the two acyl chains is attached to glycerol in ether, rather than ester, linkage. The ether-linked chain may be saturated, as in the alkyl ether lipids, or may contain a double bond between C-l and C-2, as in plasmalogens (Fig. 10-9). Vertebrate heart tissue is uniquely enriched in ether lipids about half of the heart phospholipids are plasmalogens. The membranes of halophilic bacteria, ciliated protists, and certain invertebrates also contain high proportions of... 

At least one ether lipid, platelet-activating factor, is a potent molecular signal. It is released... 

FIGURE 10-9 Ether lipids. Plasmalogens have an ether-linked alkenyl chain where most glycerophospholipids have an ester-linked fatty acid (compare Fig. 10-8). Platelet-activating factor has a long ether-linked alkyl chain at C-l of glycerol, blit C-2 is ester-linked to acetic acid,... 

The biosynthetic pathway to ether lipids, including plasmalogens and the platelet-activating factor... 

These ether lipids are all chiral molecules with an R configuration but are derivatives of the nonchiral glycerol. The carbon atoms of glycerol are numbered using the stereochemical system which is described on p. 470. The ether linkage is to the sn-1 carbon atom. Most phospholipids are derivatives of the sn-3 phosphate ester of glycerol. 

Triacylglycerols and the ether lipids described in the previous section are classified as neutral lipids. Other neutral lipids are alcohols, waxes, aldehydes, and hydrocarbons derived from fatty acids. These sometimes have specific biological functions. For example, fatty aldehydes are important in the bioluminescence of bacteria (Eq. 23-47). 

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... 

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