Alkyl Glycerolipids Research Articles

Development of a High-Performance Thin-Layer Chromatography Method for the Quantification of Alkyl Glycerolipids and Alkenyl Glycerolipids from Shark and Chimera Oils and Tissues

Ether lipids are composed of alkyl lipids with an ether bond at the sn-1 position of a glycerol backbone and alkenyl lipids, which possess a vinyl ether bond at the sn-1 position of the glycerol. These ether glycerolipids are present either as polar glycerophospholipids or neutral glycerolipids. Before studying the biological role of molecular species of ether glycerolipids, there is a need to separate and quantify total alkyl and alkenyl glycerolipids from biological samples in order to determine any variation depending on tissue or physiopathological conditions. Here, we detail the development of the first high-performance thin-layer chromatography method for the quantification of total alkyl and alkenyl glycerolipids thanks to the separation of their corresponding alkyl and alkenyl glycerols. This method starts with a reduction of all lipids after extraction, resulting in the reduction of neutral and polar ether glycerolipids into alkyl and alkenyl glycerols, followed by an appropriate purification and, finally, the linearly ascending development of alkyl and alkenyl glycerols on high-performance thin-layer chromatography plates, staining, carbonization and densitometric analysis. Calibration curves were obtained with commercial alkyl and alkenyl glycerol standards, enabling the quantification of alkyl and alkenyl glycerols in samples and thus directly obtaining the quantity of alkyl and alkenyl lipids present in the samples. Interestingly, we found a differential quantity of these lipids in shark liver oil compared to chimera. We quantified alkyl and alkenyl glycerolipids in periprostatic adipose tissues from human prostate cancer and showed the feasibility of this method in other biological matrices (muscle, tumor).

New design of cationic alkyl glycoglycerolipids toxic to tumor cells

New glycosylated alkyl glycerolipids bearing a cationic group at the C6 position of sugar moiety have been synthesized and tested as potential anticancer drugs. The compounds demonstrated cytotoxicity and selectivity against tumor cells at low micromolar concentration.

Synthesis and antitumor activity of new alkyl glycoglycerolipids

New glycosylated alkyl glycerolipids possessing antitumour activity were synthesized from 2-O-ethyl-1-O-octadecylglycerol, amino alcohols and monosaccharides.

Synthesis of new carbohydrate-containing cationic alkyl glycerolipids with antitumor activity

New non-phosphorous carbohydrate-containing cationic alkyl glycerolipids bearing a ter- minal glycosyl moiety were synthesized. An approach used for the preparation of 2-O-ethyl-1-O-octadecyl-rac-glycerol allowed us to increase the yield of this key precursor by a factor of two. The carbohydrate-containing cationic alkyl glycerolipids induced tumor cell death and minimal damage to normal cells (in particular, erythrocytes), which makes the new compounds promising for practical purposes.

Synthesis of cationic alkyl glycerolipids with heterocyclic nitrogen-containing bases as polar domains

Synthesis of new antitumor ether glycerolipids with various heterocyclic nitrogen-containing bases as polar domains is described. We propose synthetic scheme for cationic lipids containing aliphatic short-chain substituents in the heterocyclic polar head.

Studies of mutagenic activity of positively charged alkyl glycerolipids in ames test

Mutagenic activity of non-phosphorous cationic alkyl glycerolipid rac-N-{4-[(2-Methoxy-3-octadecyloxy)propyl]oxycarbonylbutyl}-N,N-dimethyl-N-(2-hydroxyethyl) ammonium iodide was evaluated. According performed Ames assay results indicated on non-mutagenic properties tested compound. Resulting data open the possibility to carry out biological study in vivo for class of ether cationic glycerolipids and further applications as a potential agent of anticancer therapy.

ChemInform Abstract: Synthesis of Alkyl Glycerolipids with Various Cationic Groups Linked Directly to the Glycerol Backbone.

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Alkyl-type glycerolipids as modulators of tumor cells destruction

The review summarizes current information on the biological activity and search of the antineoplastic mechanism of action among alkyl glycerolipids. Special attention is paid to following problems considered in experimental papers published during the last decade: selective ability phosphorus alkyl glycerolipids towards tumor cells using edelfosine and its analogues. The review contains modern information available in the literature, on a possible mechanism cytotoxic effect of such compounds.

Glycerolipids of alkyl type - modulators of tumoral cells destruction

The review is summarizes current information on biological activity and search of the antineoplastic mechanism of action of alkyl glycerolipids. Special attention is paid to following problems: selective ability phosphorus alkyl glycerolipids, antineoplastic activity, cytostatic and cytotoxic effects of edelfosine and its analogues. The review contains set of the data known for today from the literature, on the possible mechanism cytoyoxic actions of such connections.

Synthesis and biological activity of homologous piperidine-containing alkyl glycerolipids

The paper provides the synthesis of new phosphorless glycerolipids with an ether bond that contain heterocyclic bases in the polar domain. The physico-chemical characteristics and biological activity of the prepared compounds were studied.

Synthesis of Alkyl Glycerolipids with Functional Groups in Their Polar Heads

A number of alkyl glycerolipids with short-chain substituents at the C2 atom of glycerol and functional groups (carboxy and amino) in the polar head were synthesized. Cationic alkyl glycerolipids with a hydroxyl function in the hydrophilic moiety were also obtained.

Synthesis of alkyl glycerolipids with various cationic groups linked directly to the glycerol backbone

A number of positively charged lipids containing pyridinium,N-methylmorpholinium,N-methylimidazolinium, 4-N,N-dimethylaminopyridinium, and 4-N,N-dimethylcyclo-hexylammonium groups linked directly to the C(3) atom of 1,2-di-O-alkylglycerols with Br−, MsO−, and TsO− anions as counterions were synthesized.

Identification of 1-alkyl-2-acyl-3-(2′,3′-diacylglycerol)glycerols, a New Type of Lipid Class, in Harderian Gland Tumors of Mice

A new class of alkyl glycerolipids, 1-alkyl-2-acyl-3-(2',3'-diacylglycerol)glycerols, was identified in lipid extracts prepared from harderian gland tumors of mice. After saponification, this lipid class yielded 1-alkyl-3-(1'-glycerol)glycerols. Identification was based on mass spectrometry, proton nuclear magnetic resonance spectroscopy, infrared spectroscopy, and chromatography of various derivatives and appropriate standards that were synthesized. The alkyl moieties of this unique lipid class consisted of saturated aliphatic chains with chain lengths of 14 to 20 carbon atoms. The acyl moieties were mostly saturated and monounsaturated aliphatic chains ranging from 14 to 24 carbon atoms. The alkyl and acyl moieties of 1-alkyl-2-acyl-3-(2',3'-diacylglycerol)glycerols were similar to those of alkyldiacylglycerols present in the same tissue, except for the presence of monounsaturated alkyl moieties in the latter. 1-Alkyl-2-acyl-3-(2', 3'-diacylglycerol)glycerols were only found in trace amounts in the normal harderian glands of mice. The total quantity of the alkyl and acyl moieties with a chain length greater than 20 carbon atoms in the alkyldiacylglycerols from tumors were considerably lower than those found in normal harderian glands of mice. This is the first report of the presence of bisglyceryl ether lipids in mammalian tissue; its unique chemical structure is consistent with the type of ether-linked lipid products that could be synthesized in the reaction catalyzed by alkyldihydroxyacetone-P synthase.

Formation of optically active ether lipids from race-mic-1-O-tetradecylglycerol in plant cell cultures

Photomixotrophic rape cells in culture specifically incorporate 1- O-tetradecyl- sn-glycerol from a racemic mixture into complex alkyl glycerolipids. Thus, both neutral and ionic 1- O- alkyl-2- O-acyl- sn-glycerolipids with defined alkyl moieties can be prepared from racemic mixtures of alkylglycerols.

On the role of long-chain aldehydes in mammalian plasmalogen biosynthesis.

[1-3H, 1-14C]Palmitaldehyde (3H:14C = 15) was injected intracerebrally to 18-day-old rats and incorporation of radioactivity into brain lipids was followed over a 24-h period. The substrate was metabolized primarily by oxidation to palmitic acid with loss of tritium and, to a lesser extent, by reduction to hexadecanol. The alkyl moieties of the ethanolamine phospholipids showed considerably lower 3H:14C ratios than the substrate, indicating a substantial participation in either lipid synthesis by tritium-free alcohols derived from 14C-labeled fatty acids. Virtually no 3H radioactivity was found in alkenyl moieties, indicating stereospecificity of both reduction of aldehyde and dehydrogenation of alkyl to alkenyl glycerolipid. The data are consistent with the general concept that plasmalogen biosynthesis proceeds exclusively through fatty alcohols and alkyl glycerolipids and that fatty aldehydes cannot be utilized directly.

Biosynthesis and utilization of long-chain alcohols in rat brain: Aspects of chain length specificity

Chain Length specificity in alkyl glycerolipid biosynthesis was studied with microsomal preparations from 19-day-old rat brain. Saturated alcohols ranging from 12 to 22 carbon atoms were incorporated at different rates into alkyl dihydroxyacetone phosphate, the first intermediate in ether lipid biosynthesis. The rate of alkyl dihydroxyacetone phosphate formation was highest with hexadecanol and alcohols of either longer or shorter chain length were utilized much less efficiently. The monounsaturated octadecenol was incorporated more readily than any of the saturated alcohols. Rat brain microsomes were also found to reduce saturated fatty acids ranging from 12 to 22 carbon atoms, and oleic acid to the corresponding alcohols in the presence of ATP, coenzyme A, Mg 2+, and NADPH. Chain length selectivity in the reduction was less pronounced than that in alkyl DHAP synthesis. The data indicate that the alkyl and alk-1-enyl composition of rat brain ether lipids is controlled by substrate specificity in the formation of both fatty alcohol and alkyl dihydroxyacetone phosphate.

Structural specificity in ether lipid biosynthesis. Formation of hydroxyalkyl and oxoalkyl glycerophosphatides.

Structural specificity of alkyl glycerolipid formation was studied in myelinating rat brain. 1,2-[2-14-C,2-3-H]Heptadecanediol, 1,2-[1-14-C]octadecanediol, and 1-O-2-hydroxy-[1-14-C]heptadecyl-rac-glycerol were administered intracerebrally and their incorporation into phospholipids was determined after time periods ranging from 6 to 48 hours. Experimental evidence is presented to support the following conclusions. (a) Long chain 1,2-alkanediols serve as direct precursors of the 2-hydroxyalkyl moieties of both choline and ethanolamine glycerophosphatides. (b) 1,2-Alkanediols are oxidized to 1-hydroxy-2alkanones which serve as precursors of the 2-oxoalkyl moieties of the glycerophosphatides. (c) Oxidations of hydroxy groups and reductions of oxo groups do not occur at the phospholipids, but are confined to 1,2-alkanediols and 1-hydroxy-2-alkanones, respectively. (d) Metabolic degradation of 1,2-alkanediols proceeds by oxidation to the corresponding 2-hydroxy and/or 2-oxo fatty acids and decarboxylation.

Tetrahydropteridine-dependent cleavage enzyme for O-alkyl lipids: substrate specificity

The tetrahydropteridine-requiring enzyme in rat liver microsomes that oxidatively cleaved the O-alkyl moiety of glycerolipids does not utilize alkyl glycerolipid substrates that contain carbonyl, acyl, or phosphate groups on the glycerol portion. However, the ether linkage in rac and 1-, 2-, or 3-isomeric forms of alkylglycerols and 1-alkyl- sn-glycero-3-phosphorylethanolamine is readily cleaved by the pteridine-requiring enzyme. Therefore, it appears that hydrolytic enzymes play an essential role in conjunction with the cleavage enzyme in the regulation of cellular levels of O-alkyl moieties in glycerolipids.

Chemical identification and enzymatic synthesis of a newly discovered lipid class—Hydroxyalkylglycerols

We have isolated and identified a new class of alkyl glycerolipids in lipid extracts prepared from the pink portion of the harderian glands of rabbits. After LiAlH 4 reduction, the esterified lipid yields a hydroxyalkylglycerol. Identification was based on chromatography, infrared spectroscopy, and mass spectra of various derivatives of this lipid and of standards prepared chemically. The isomers of the hydroxyalkylglycerols isolated consisted of O-hexadecyl moieties with hydroxyl groups at C-10 and C-11 and of O-octadecyl moieties with hydroxyl groups at C-11 and C-12. In the natural state all of the hydroxyl groups are thought to be esterified with aliphatic moieties, and this lipid class accounts for approximately 80% of the total lipids of the pink harderian gland of rabbits. Enzymatic experiments demonstrated that [1- 3H]octadecane-1,12-diol was readily incorporated into the hydroxyalkylglycerols when dihydroxyacetone-P, CoA, ATP, Mg 2+, and the microsomal fraction of the pink harderian gland were included in the incubations. Thus, it appears that the ether linkage of hydroxyalkylglycerols is biosynthesized in a manner analogous to that previously described for glycerolipids containing unsubstituted O-alkyl moieties.

Synthesis of Acyl Dihydroxyacetone Phosphates and Related Derivatives

The chemical syntheses of 1-O-palmitoyl- and 1-O-acetyl-2,2-dimethoxypropane-3-phosphate cyclohexylammonium salt and 1-O-palmitoyl-2,2-dimethoxypropane-3-O-phosphoryl-ethanolamine are reported. The acyl dihydroxyacetone phosphates can serve as intermediates in the pathway for the biosynthesis of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and alkyl glycerolipids.