Synthesis of thio- and selenophospholipids from 2,2,5,5-tetra(hydroxymethyl)cyclopentanone

New phospholipids, thio- and selenoanalogues of phosphatidic acids, were synthesized on the basis of 2,2,5,5-tetra(hydroxymethyl)cyclopentanone. The starting tetraol monoketal was phosphorylated with amidophosphorous acid chlorides to protected polyol amidophosphites, which were further sulfurized or selenized to phosphoacetals. These were directly acylated with fatty acid chlorides to thio- and selenoanalogues of phospholipids.     

Synthesis of acetal and phosphocyclic methriolipids

The first representatives of acetal and phosphocyclic lipids based on methriol (2-hydroxymethyl-2-methyl-1,3-propanediol) were synthesized. The interaction of the starting triol with higher aldehydes gave the corresponding alkylidene compounds, which were subsequently phosphorylated by derivatives of phosphorous acid. The intermediate amidophosphites were treated without isolation with iodobenzene, sulfur, or selenium to give phosphoacetals and their thio-and selenoanalogues, which are acetal phospholipids. Methriol bicyclophosphite was also used in the lipid synthesis. It was acylated with palmitoyl chloride at one of the bicyclic oxygen atoms. Alcoholysis of acyl polyol chlorophosphite resulted in a phospholipid, which was oxidized with sulfur to give thionphosphate.     

Dipentaerythritol in the Synthesis of New-Type Phospholipids

The first representatives of phospholipids of new types were synthesized on the basis of dipentaerythritol, 2,2′-[oxybis(methylen)]bis(hydroxymethyl))-1,3-propandiol. The starting polyol was phosphorylated with hexaethylphosphoric triamide to biphosphite, which was converted into thio- and selenophosphates by treatment with sulfur or selenium. The phosphoacetals were transformed into thio- and selenoanalogues of phospholipids by direct acylation with higher fatty acid chlorides.     

Dipentaerythritol in the synthesis of the new type of phospholipids

The first representatives of phospholipids of new types were synthesized on the basis of dipentaerythritol, 2,2'-[oxybis(methylen)]bis(hydroxymethyl))-1,3-propandiol. The starting polyol was phosphorylated with hexaethylphosphoric triamide to biphosphite, which was converted into thio- and selenophosphates by treatment with sulfur or selenium. The phosphoacetals were transformed into thio- and selenoanalogues of phospholipids by direct acylation with higher fatty acid chlorides. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.     

The synthesis of thio- and selenoanalogues of phospholipids on the basis of 2-butyl-2-hydroxymethyl-1,3-propanediol

New analogues of nonglycerol polyol phospholipids were prepared on the basis of 1,1,1-trimethylolethane. Amidophosphites and cyclophosphites of the isopropylidene derivative of this polyol were intermediates in the syntheses. They were treated with sulfur or selenium. Phosphoacetals were converted into lipids by the direct acylation with higher fatty acid chlorides. The triol bicyclophosphite was also used in the lipid syntheses. It was directly acylated at the oxygen atom, the resulting acylpolyol of chlorophosphite was then converted into phospholipids by alcoholysis and subsequent treatment with sulfur.     

The Synthesis of Thio- and Selenoanalogues of Phospholipids on the Basis of 2-Butyl-2-Hydroxymethyl-1,3-Propanediol

New analogues of nonglycerol polyol phospholipids were prepared on the basis of 1,1,1-trimethylolpenthane. Amidophosphites and cyclophosphites of the isopropylidene derivative of this polyol were intermediates in the syntheses. They were treated with sulfur or selenium. Phosphoacetals were converted into lipids by direct acylation with higher fatty acid chlorides. The triol bicyclophosphite was also used in the lipid syntheses. It was directly acylated at the oxygen atom, and the resulting acylpolyol of chlorophosphite was then converted into phospholipids by alcoholysis and subsequent treatment with sulfur.__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 4, 2005, pp. 414–419.Original Russian Text Copyright © 2005 by Savin, Kutsemako.     

Ascorbic acid and other chelating agents in the trace-mineral nutrition of the aphid Myzus persicae on artificial diets

Growth of the aphidMyzus persicae fed artificial diets in which the required trace minerals (Fe, Cu, Mn, and Zn) were incorporated as chlorides was compared to growth on diets in which the minerals were supplied as sodium EDTA complexes. If the mineral chlorides were allowed to interact with L ascorbic acid prior to their incorporation into a diet, much less ascorbic acid was needed than if the ascorbic acid was added after incorporation of the mineral chlorides into a diet. Low levels of D ascorbic acid or citric acid acted similarly to L ascorbic acid. This was presumably by chelating the minerals. The complexes thus formed not only maintained the minerals in solution for ingestion but appeared to facilitate their utilization by the aphids. However, higher levels of L ascorbic acid were needed by the insects, presumably for purposes other than trace-mineral nutrition, when they were maintained for longer periods on the diets.     

An investigation of the use of recovered vegetable oil for the preparation of starch thermoplastics

The main components (90%) in recovered vegetable oil (RVO) are esters of higher carboxylic acids and glycerol (triglycerides) which consist of three fatty acids: oleic (C18:1, Z), palmitic (C16:0) and linoleic (C18:2, Z) in the ratio 2.8:1.4:1. RVO may provide a low cost new supply of unsaturated fatty acid chlorides. Modification of potato starch using the mixture of fatty acid chlorides derived from RVO and using acid chlorides of the two major pure component acids has been performed. Films were prepared from the starch esters and mechanical properties tested. Commercially available potato starch, modified to DS-value 1.5 with RVO-derived acyl chlorides, was thermoplastic with a maximum tensile strength of 1.4 MPa and an elongation at break of 54%.     

Effect of Palmitic and Lauric Acids on the Phospholipid Bilayer Membrane Conductivity

Palmitic acid increased the conductivity of BLM from mitochondrial phospholipids when they were dissolved in a mixture of decane and chlorodecane, and was ineffective when phospholipids were dissolved in decane. Lauric acid produced an increase in the membrane conductivity independently of the phospholipid type in the membrane-forming solutions (mitochondrial phospholipids, asolectin, lecithin with cholesterol) and their solvents (decane or decane with chlorodecane). The results show that discrepancies between published data concerning fatty acid effects on the BLM conductivity may be explained by differences in phospholipids, their solvents and fatty acid used.     

The fatty acid composition of the serum phospholipids of children with sickle cell disease in Nigeria

The purpose of this study was to determine the fatty acid composition of the serum phospholipids of children with sickle cell disease (SCD) in Nigeria and to compare the relative fluidity of the acyl chains of the serum phospholipids of controls versus the subjects with SCD. It is widely accepted that the fatty acid composition of an individual's serum phospholipids reflects that of their tissue phospholipids. An alteration in the fatty acid composition of membrane phospholipids could affect critical membrane-dependent enzymes and processes (e.g., ion and solute transport, hormone-receptor interactions, signal transduction pathways). We found a significant reduction in the content of polyunsaturated n-3 fatty acids in the phospholipids of subjects with SCD which could result in a reduction of the fluidity of their tissue membranes. Specifically, there was a 40-50% reduction in the proportion of total n-3 fatty acids in subjects with SCD. On the basis of calculated melting points and double bond indices of the acyl chains of the serum phospholipids, the phospholipids of the children with SCD are less fluid relative to those of their healthy counterparts. In addition, we determined that linoleic acid, arachidonic acid, and stearic acid were the major determinants of the fluidity of the acyl chains of the serum phospholipids of the healthy controls and children with SCD.     

Inadequacy of myelin phospholipids for restoration of succinoxidase activity in lipid-depleted mitochondria

Succinoxidase activity in lipid-depleted mitochondria was not restored efficiently by mixed myelin phospholipids at difference with the natural mitochondrial phospholipids, yeast phospholipids, and Asolectin. Since similar differences in activity were present between pure phosphatidyl-ethanolamine fractions separated from myelin phospholipids and Asolectin, they should be due to the different fatty acid composition of the phospholipids. In contrast with the differentability in restoration of succionoxidase, all the phospholipids studied were bound to the lipid-depleted membranes to similar extents.     

Alteration of fatty acid composition of LM cells by lipid supplementation and temperature.

Alteration of the fatty acid composition of monolayer cultures of LM cells grown in chemically defined medium was achieved by supplementation with fatty acids complexed to bovine serum albumin. Phospholipids containing up to 40% linoleate were found in cells grown in medium containing 20 mu g of linoleate/ml. Incorporation of linoleate into phospholipids reached a plateau after 12-24 hr, and cells remained viable for at least 3-4 days. Although linoleic, linolenic, and arachidonic acids were incorporated into LM cells equally well, only the latter was elongated by these cells under these experimental conditions. Nonadecanoic acid was incorporated to a lesser extent than the polyunsaturated fatty acids. Phosphatidylcholine and phosphatidylethanolamine of LM cells had different fatty acid compositions; phosphatidylethanolamine contained more longer chain and unsaturated fatty acids. Cells were also grown in the absence of choline and presence of choline analogs such as N,N-dimethylethanolamine, N-methylethanolamine, 3-amino-1-propanol, and 1-2-amino-1-butanol. The analog phospholipids in these cells had fatty acid compositions which were intermediate between those of phosphatidylethanolamine and phosphatidylcholine of control cells grown in the presence of choline. Linoleate was found in both phosphatidylcholine and phosphatidylethanolamine of cells supplemented with linoleate. The sphingolipid fraction of these cells, however, did not contain significant amounts of linoleate. When linoleate was present in the phospholipids, compensatory decreases in the oleate and palmitoleate content of phospholipids were observed. Lowering of the growth temperature to 28 degrees produced an increase in unsaturate fatty acid content of the phospholipids. When linoleate was supplied to cells grown at 28 degrees, there was no further increase in the unsaturated fatty acid composition of the phospholipids. Using both fatty acid supplementation and lowered growth temperature, LM cell membranes can be produced which have phospholipids with vastly different fatty acid compositions.     

Essential fatty acids in erythrocyte phospholipids during pregnancy and at delivery in mothers and their neonates: comparison with plasma phospholipids

Evidence that the essential fatty acid (EFA) status during pregnancy and at birth may not be optimal is mainly based on fatty acid profiles of maternal and neonatal plasma phospholipids. However, erythrocyte phospholipids may be more reliable than plasma phospholipids to reflect the EFA status of an individual. Therefore, the present study compares the levels of EFA and of their derivatives (LCPUFA) in erythrocyte and plasma phospholipids collected during pregnancy and at delivery of 184 women and of their infants at birth. In general, the relative concentrations of erythrocyte and plasma phospholipid fatty acids (% of total fatty acids) were strongly correlated, but not at early pregnancy. The overall changes in fatty acid concentrations during pregnancy were qualitatively comparable between erythrocytes and plasma, although the comparability became less towards the end of pregnancy. The changes in absolute amounts (mg/l) of fatty acids in erythrocyte and plasma phospholipids also compare quite well till 32 weeks of gestation, but not thereafter. Most maternal-neonatal differences in relative fatty acid concentrations are qualitatively comparable for erythrocyte and plasma phospholipids. However, significant differences were observed for the absolute amounts of arachidonic and docosahexaenoic acids. No matter these differences, plasma and erythrocyte phospholipids seem equally suitable to reliably quantify the more functional EFA and LCPUFA status based on fatty acid ratios. Correlations between neonatal and maternal fatty acid values at delivery/birth are highly significant in erythrocyte as well as plasma phospholipids. Neonatal erythrocyte (but not plasma) values also correlated strongly with maternal values at early pregnancy. Therefore, the neonatal EFA and LCPUFA status might be predicted on the basis of EFA and LCPUFA concentrations of maternal erythrocyte phospholipids at early pregnancy.     

Effect of retinoic acid on the acylation of phospholipids in granulocytes in vitro

The influence of retinoic acid on the incorporation of [1-14C]palmitic acid and [1-14C]arachidonic acid into phospholipids was examined in guinea pig peritoneal granulocytes. All-trans-retinoic acid inhibited the incorporation of both fatty acids into phosphatidic acid and phosphatidylinositol. However, it stimulated the incorporation of both fatty acids into phosphatidylcholine but not other phospholipids. All-trans-retinoic acid was more effective than 13-cis-retinoic acid. The influence of all-trans-retinoic acid on the acylation of phospholipids was concentration-dependent with significant effect occurring at 2.1 microM. The loss of labeled fatty acids from prelabeled phospholipids and the transport of labeled fatty acids into granulocytes were not responsive to the presence of retinoic acid in the incubation media. These results suggest that retinoic acid may affect the activities of acyltransferases involved in the synthesis of phosphatidic acid, phosphatidylinositol and phosphatidylcholine.     

Synthesis, properties, and photodynamic properties in vitro of heavy-chalcogen analogues of tetramethylrosamine

Thio and seleno analogues of tetramethylrosamine were prepared by the directed-metalation/cyclization of the corresponding N,N-diethyl 2-(3-dimethylaminophenylchalcogeno)-4-dimethylaminobenzamide to the 2,7-bis-(N,N-dimethylamino)-9H-chalcogenoxanthen-9-one followed by the addition of phenylmagnesium bromide, dehydration, and ion exchange to the chloride salt. The thio and seleno tetramethylrosamines had longer wavelengths of absorption and higher quantum yields for the generation of singlet oxygen than tetramethylrosamine. Both the thio and selenoanalogues of tetramethylrosamine were efficient photosensitizers against R3230AC rat mammary adenocarcinoma cells in vitro.     

Fatty acid synthesis in Escherichia coli is indirectly inhibited by phenethyl alcohol.

Experiments were performed to determine how phenethyl alcohol inhibits phospholipid synthesis in E. coli. At a nonbacteriostatic concentration, the drug reduces the rate of de novo fatty acid and phospholipid synthesis by 60 to 70%. The inhibition of fatty acid synthesis was found to be a secondary consequence of the inhibition of phospholipid synthesis. Phenethyl alcohol reduces the rate of incorporation of exogenous fatty acids into the phospholipids of a fatty acid auxotroph by 60%. These results indicate that this drug controls phospholipid synthesis beyond the level of fatty acid synthesis. Phenethyl alcohol inhibits the synthesis of phospholipids containing saturated fatty acids to a greater extent than it does the synthesis of phospholipids containing unsaturated fatty acids. It controls the synthesis of phospholipids containing saturated fatty acids at both the level of fatty acid synthesis and the level of incorporation of the saturated fatty acids into phospholipids. The synthesis of phospholipids containing unsaturated fatty acids is inhibited at the level of incorporation of the fatty acids into phospholipids.     

Phospholipids and thromboplastins in various sections of the brain normally and in excitation states]

The level of the neutral and acid phospholipids and thromboplastic activity of various portions of the rabbit brain were studied under normal conditions and following adrenaline stimulation. The level of total phospholipids, neutral phospholipids, and the ratio of neutral to acid phospholipids, thromboplastic activity and its increase following incubation of homogenates of the brain tissue of normal and adrenaline-treated animals were found to be distributed in the following descending order: the medulla oblongata, cerebellum, cerebral hemispheres. Adrenaline decreased the thromboplastic activity and induced changes in the neutral and acid phospholipid levels. The role of phospholipids in the biosynthesis of various components of the blood clotting and anticoagulant systems are discussed.     

Changes in plasma lipid composition induced by coconut oil. Effects of dipyridamole

The comparative effects of 10-20% coconut oil feeding on fatty acid composition of the main lipid classes of chick plasma have been studied with and without simultaneous treatment with dipyridamole in order to clarify the hypolipidemic role of this drug. Coconut oil drastically increased the percentages of lauric and myristic acids in free fatty acid and triacylglycerol fractions, whereas these changes were less pronounced in phospholipids and cholesterol esters. The percentage of arachidonic acid was higher in plasma phospholipids than in the other fractions and was significantly decreased by coconut oil feeding. Linoleic acid, the main fatty acid of cholesterol esters, was drastically increased by coconut oil feeding. Changes induced by the simultaneous administration of dipyridamole were more pronounced in the phospholipids and cholesterol esters than in the other fractions. The fall observed in linoleic acid levels after dipyridamole treatment may be of interest for a lower production of its derived eicosanoids, especially in plasma phospholipids and cholesterol esters.     

Involvement of phospholipids in polyunsaturated Fatty Acid synthesis in developing soybean cotyledons

Developing soybean (cv. Dare) cotyledons harvested at 30 days after flowering were pulse-labeled with [1-(14)C]oleoyl-CoA. The metabolic interrelation of radiolabeled unsaturated fatty acids between the major glycerolipid classes was determined at various time intervals. At chase time zero, [(14)C]oleic acid accounted for 99.2% of the total glycerolipid radioactivity, and phospholipids contained 92% of the total incorporated radioactivity. With time, phospholipids were metabolized in triacylglycerol biosynthesis and radioactivity was detected in polyunsaturated fatty acids. The hypothesis that phospholipids were metabolic intermediates in polyunsaturated fatty acid biosynthesis was tested by comparing the theoretical and the actual amount of radiolabeled oleic acid that was associated with triacylglycerol as a function of time. The radioactive oleic acid found in triacylglycerol at various intervals was derived from phospholipids via a diacylglycerol intermediate. Assuming no phospholipid desaturation, the potential or theoretical amounts of [(14)C]oleic acid that could be transferred to triacylglycerol from phospholipids was defined by a system of differential equations. The results demonstrated that the decline in [(14)C]oleic acid from phospholipid after long chase intervals was equal to the total amount of radioactive unsaturated fatty acids found in neutral lipids. The difference between the theoretical and actual amounts of [(14)C]oleic acid present in triacylglycerol after long time intervals was equal to the amount of radioactivity present in polyunsaturated fatty acids. Based upon those findings in soybeans, the desaturation of oleic acid associated with phospholipids was highly probable.     

In vitro effect of free bile acids on the bile canalicular membrane phospholipids in the rat.

Liver cell plasma membranes of male rats were isolated and separated into two fractions, one rich in bile canalicular membranes (BCM) and the other comprising the rest of the plasma membrane (PM). Aliquots of BCM, PM, and microsomes were incubated with deoxycholic, chenodeoxycholic, or cholic acid at bile acid - membrane phospholipid mole ratios up to 100, and the phospholipid solubilization from the PM and from microsomes was linear and apparently nonselective, while that from BCM was biphasic and distinctly selective. Phosphatidyl choline and phosphatidyl ethanolamine made up 90% of the phospholipids solubilized from the BCM at a bile acid - membrane phospholipid mole ratio sufficient to solubilize about 50% of the total phospholipids of the BCM. Of particular interest was the observation that the molecular species and fatty acid composition of the phospholipids solubilized from the BCM under these experimental conditions were similar to those of bile obtained from the same animal, and were quite unlike those solubilized at higher bile acid - phospholipids mole ratios. The data are discussed in terms of the mechanism of the biliary secretion of phospholipids.