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Biochimica Et Biophysica Acta Dec 2009Interaction between the bioactive compounds nicotinamide and picolinamide and phospholipids (phosphatidylcholines and phosphatidylethanolamines) was investigated by a...
Interaction of nicotinamide and picolinamide with phosphatidylcholine and phosphatidylethanolamine membranes: a combined approach using dipole potential measurements and quantum chemical calculations.
Interaction between the bioactive compounds nicotinamide and picolinamide and phospholipids (phosphatidylcholines and phosphatidylethanolamines) was investigated by a combined approach using dipole potential measurements and quantum chemical calculations. It is shown that nicotinamide and picolinamide interactions with phosphatidylcholines are of two main types: (i) specific interactions with the phosphate group of the lipid, for which H-bonding between NH(2) group of the substrate and the phosphate plays a dominant role, (ii) conjugated less specific weaker interactions involving both the phosphate and carbonyl groups of the head group, which propagate to the lipid alkyl chains and increase their conformational disorder. For phosphatidylethanolamines, picolinamide was found to decrease the dipole potential of the membrane in a similar way as for phosphatidylcholines, while nicotinamide is ineffective. These findings are correlated with the specific properties of phosphatidylethanolamines (reduced exposure of phosphate groups) and structural differences in the two substrates, in particular: different separation of the nitrogen atoms in the molecules, existence of a strong intramolecular hydrogen bond in picolinamide (NH...N ((ring))), which is absent in nicotinamide, and non-planarity of nicotinamide molecules, in contrast to picolinamide ones. Additional information on the lipid/substrate interactions was extracted from the analysis of the changes produced in the relevant vibrational frequencies of the lipid and substrate upon binding. The present study gives molecular support to the argument that changes of dipole potentials are due to effects on the constitutive dipolar PO and CO groups. In addition, it is also shown that according to the specific binding of the substrate to one or both of those, the conformational state of the acyl chains may be affected. These entropy effects may be in the origin of the well-known interdependence of the properties of one monolayer with respect to the other in bilayer membranes.
Topics: Amides; Hydrogen Bonding; Membranes, Artificial; Models, Chemical; Niacinamide; Phosphatidylcholines; Picolinic Acids
PubMed: 19840772
DOI: 10.1016/j.bbamem.2009.10.007 -
Biochimica Et Biophysica Acta.... Oct 2022Hybrid membranes built from phospholipids and amphiphilic block copolymers seek to capitalize on the benefits of both constituents for constructing biomimetic interfaces...
Hybrid membranes built from phospholipids and amphiphilic block copolymers seek to capitalize on the benefits of both constituents for constructing biomimetic interfaces with improved performance. However, hybrid membranes have not been formed or studied using the droplet interface bilayer (DIB) method, an approach that offers advantages for revealing nanoscale changes in membrane structure and mechanics and offers a path toward assembling higher-order tissues. We report on hybrid droplet interface bilayers (hDIBs) formed in hexadecane from binary mixtures of synthetic diphytanoyl phosphatidylcholine (DPhPC) lipids and low molecular weight 1,2 polybutadiene-b-polyethylene oxide (PBPEO) amphiphilic block copolymers and use electrophysiology measurements and imaging to assess the effects of PBPEO in the membrane. This work reveals that hDIBs containing up to 15 mol% PBPEO plus DPhPC are homogeneously mixtures of lipids and polymers, remain highly resistive to ion transport, and are stable-including under applied voltage. Moreover, they exhibit hydrophobic thicknesses similar to DPhPC-only bilayers, but also have significantly lower values of membrane tension. These characteristics coincide with reduced energy of adhesion between droplets and the formation of alamethicin ion channels at significantly lower threshold voltages, demonstrating that even moderate amounts of amphiphilic block copolymers in a lipid bilayer provide a route for tuning the physical properties of a biomimetic membrane.
Topics: Alamethicin; Lipid Bilayers; Phosphatidylcholines; Phospholipids
PubMed: 35718208
DOI: 10.1016/j.bbamem.2022.183997 -
International Journal of Molecular... Aug 2014This paper presents the synthesis of structured phosphatidylcholine (PC) enriched with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) by transesterification...
This paper presents the synthesis of structured phosphatidylcholine (PC) enriched with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) by transesterification of DHA/EPA-rich ethyl esters with PC using immobilized phospholipsase A1 (PLA1) in solvent-free medium. Firstly, liquid PLA1 was immobilized on resin D380, and it was found that a pH of 5 and a support/PLA1 ratio (w/v) of 1:3 were the best conditions for the adsorption. Secondly, the immobilized PLA1 was used to catalyze transesterification of PC and DHA/EPA-rich ethyl esters. The maximal incorporation of DHA and EPA achieved was 30.7% for 24 h of reaction at 55 °C using a substrate mass ratio (PC/ethyl esters) of 1:6, an immobilized PLA1 loading of 15% and water dosage of 1.25%. Then the reaction mixture was analyzed by 31P nuclear magnetic resonance (NMR). The composition of reaction product included 16.5% PC, 26.3% 2-diacyl-sn-glycero-3-lysophosphatidylcholine (1-LPC), 31.4% 1-diacyl-sn-glycero-3-lysophosphatidylcholine (2-LPC), and 25.8% sn-glycerol-3-phosphatidylcholine (GPC).
Topics: Docosahexaenoic Acids; Eicosapentaenoic Acid; Enzymes, Immobilized; Esterification; Lysophosphatidylcholines; Phosphatidylcholines; Phospholipases A1
PubMed: 25170810
DOI: 10.3390/ijms150915244 -
European Journal of Biochemistry Aug 198115 strains of hydrogen-oxidizing bacteria were grown heterotrophically, harvested during the stationary phase of growth, and analyzed for their principal phospholipids....
15 strains of hydrogen-oxidizing bacteria were grown heterotrophically, harvested during the stationary phase of growth, and analyzed for their principal phospholipids. All strains - with the exception of Corynebacterium autotrophicum strain SA 32 and Pseudomonas pseudoflava - contained phosphatidylcholine as a major constituent. It is concluded that the presence of phosphatidylcholine is neither characteristic of a peculiar bacterial genus or family, nor is it absolutely correlated to the ability to oxidize hydrogen. The phosphatidylcholines of all strains contain C19 cyclopropane acid which is, in some strains, predominantly located at C-2 position of the glycerol moiety.
Topics: Bacteria; Hydrogen; Oxidation-Reduction; Phosphatidylcholines; Species Specificity
PubMed: 7285913
DOI: 10.1111/j.1432-1033.1981.tb05503.x -
The American Journal of Clinical... Dec 2020Lipid metabolism in pregnancy delivers PUFAs from maternal liver to the developing fetus. The transition at birth to diets less enriched in PUFA is especially...
BACKGROUND
Lipid metabolism in pregnancy delivers PUFAs from maternal liver to the developing fetus. The transition at birth to diets less enriched in PUFA is especially challenging for immature, extremely preterm infants who are typically supported by total parenteral nutrition.
OBJECTIVE
The aim was to characterize phosphatidylcholine (PC) and choline metabolism in preterm infants and demonstrate the molecular specificity of PC synthesis by the immature preterm liver in vivo.
METHODS
This MS-based lipidomic study quantified the postnatal adaptations to plasma PC molecular composition in 31 preterm infants <28 weeks' gestational age. Activities of the cytidine diphosphocholine (CDP-choline) and phosphatidylethanolamine-N-methyltransferase (PEMT) pathways for PC synthesis were assessed from incorporations of deuterated methyl-D9-choline chloride.
RESULTS
The concentration of plasma PC in these infants increased postnatally from median values of 481 (IQR: 387-798) µM at enrollment to 1046 (IQR: 616-1220) µM 5 d later (P < 0.001). Direct incorporation of methyl-D9-choline demonstrated that this transition was driven by an active CDP-choline pathway that synthesized PC enriched in species containing oleic and linoleic acids. A second infusion of methyl-D9-choline chloride at day 5 clearly indicated continued activity of this pathway. Oxidation of D9-choline through D9-betaine resulted in the transfer of 1 deuterated methyl group to S-adenosylmethionine. A very low subsequent transfer of this labeled methyl group to D3-PC indicated that liver PEMT activity was essentially inactive in these infants.
CONCLUSIONS
This study demonstrated that the preterm infant liver soon after birth, and by extension the fetal liver, was metabolically active in lipoprotein metabolism. The low PEMT activity, which is the only pathway for endogenous choline synthesis and is responsible for hormonally regulated export of PUFAs from adult liver, strongly supports increased supplementation of preterm parenteral nutrition with both choline and PUFAs.
Topics: Adaptation, Physiological; Choline; Cohort Studies; Fatty Acids, Unsaturated; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Isotope Labeling; Male; Phosphatidylcholines
PubMed: 32778895
DOI: 10.1093/ajcn/nqaa207 -
The Journal of Nutrition Mar 2008There is evidence to suggest that folate, homocysteine, or both affect the (n-3) long chain PUFA composition of tissues; however, this evidence is derived largely from... (Randomized Controlled Trial)
Randomized Controlled Trial
Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine.
There is evidence to suggest that folate, homocysteine, or both affect the (n-3) long chain PUFA composition of tissues; however, this evidence is derived largely from experiments with animals and small observational studies in humans. Results from randomized controlled trials are needed. The objective of this study was to determine whether homocysteine lowering with a B vitamin supplement affects the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine. We conducted a double-blind, placebo-controlled, randomized clinical trial involving 253 participants, 65 y or older, with plasma homocysteine concentrations of at least 13 micromol/L. Participants in the vitamin group (n = 127) took a daily supplement containing 1000 microg folate, 500 microg vitamin B-12, and 10 mg vitamin B-6 for 2 y. The fatty acid composition of plasma phosphatidylcholine was measured at baseline and at 2 y. Plasma homocysteine concentrations during the course of the study were 4.4 micromol/L lower in the vitamin group than in the placebo group. The proportions of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids in plasma phosphatidylcholine did not differ between the vitamin and placebo groups at 2 y; the mean differences after adjusting for baseline values and sex were -0.03 (99% CI: -0.22, 0.16), 0.03 (99% CI: -0.03, 0.09), and -0.02 (99% CI: -0.27, 0.24) mol%, respectively. Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 had no effect on the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine.
Topics: Aged; Double-Blind Method; Fatty Acids, Omega-3; Female; Folic Acid; Homocysteine; Humans; Male; Phosphatidylcholines; Time Factors; Vitamin B 12; Vitamin B 6
PubMed: 18287365
DOI: 10.1093/jn/138.3.551 -
Biophysical Journal Jul 2022The (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) moiety tethered to the headgroup of phosphatidylcholine (PC) lipid is employed in spin labeling electron paramagnetic...
The (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) moiety tethered to the headgroup of phosphatidylcholine (PC) lipid is employed in spin labeling electron paramagnetic resonance spectroscopy to probe the water dynamics near lipid bilayer interfaces. Due to its amphiphilic character, however, TEMPO spin label could partition between aqueous and lipid phases, and may even be stabilized in the lipid phase. Accurate assessment of the TEMPO-PC configuration in bilayer membranes is essential for correctly interpreting the data from measurements. Here, we carry out all-atom molecular dynamics (MD) simulations of TEMPO-PC probe in single-component lipid bilayers at varying temperatures, using two standard MD force fields. We find that, for a dipalmitoylphosphatidylcholine (DPPC) membrane whose gel-to-fluid lipid phase transition occurs at 314 K, while the TEMPO spin label is stabilized above the bilayer interface in the gel phase, there is a preferential location of TEMPO below the membrane interface in the fluid phase. For bilayers made of unsaturated lipids, 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), which adopt the fluid phase at ambient temperature, TEMPO is unequivocally stabilized inside the bilayers. Our finding of membrane phase-dependent positioning of the TEMPO moiety highlights the importance of assessing the packing order and fluidity of lipids under a given measurement condition.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Cyclic N-Oxides; Lipid Bilayers; Phosphatidylcholines; Spin Labels; Water
PubMed: 35651317
DOI: 10.1016/j.bpj.2022.05.044 -
Chemistry and Physics of Lipids Jan 2017Syntheses and enzymological characterization of fluorogenic substrate probes targeting secretory phospholipase A (sPLA) for detection and quantitative assays are...
Syntheses and enzymological characterization of fluorogenic substrate probes targeting secretory phospholipase A (sPLA) for detection and quantitative assays are presented. Three fluorogenic phosphatidylcholine analogs PC-1, PC-2, and PC-3 each containing the duo of 7-mercapto-4-methyl-coumarin fluorophore and 2,4-dinitroanaline quencher on either tail were synthesized from (R)-3-amino-1,2-propanediol and R-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol. These small reporter groups are advantageous in preserving natural membrane integrity. Phosphocholine was incorporated into the sn-3 position of the glycerol backbone. Acyl amino group at the sn-1 position in PC-1 and PC-2 is meant to block sPLA. The sn-1 and sn-2 positions of the glycerol backbone in PC-1 have a quencher terminated 12-carbon chain and fluorophore terminated 11-carbon chain respectively. PC-2 has a quencher terminated 3-carbon chain at the sn-2 and chain terminating fluorescent reporter at the sn-1 positions. PC-3 resembles PC-1 except for an ester instead of amide at the sn-1 position, because of which it is more similar to natural phospholipids than PC-1. It was designed to elucidate the effect of replacing the ester group with amide by comparing its hydrolysis rate with that of PC-1. Design principles apply to synthesis of other labeled phospholipids. Enzymological characterization using bee-venom sPLA was performed by a fatty-acid-binding-protein fluorescence assay and by pH-Stat method in which the amount of fatty acid released by hydrolysis is given by the amount of base required to maintain a constant pH of 8.0. Hydrolytic activity toward PC-1 and PC-3 were each about 238±25μmol/mg/min and 537μmol/mg/min on unmodified phospholipid. Ester to amide change did not affect hydrolysis rates. Activity toward PC-2 was about 45-μmol/mg/min. PC-1 and PC-3 show potential for targeted real-time spectrophotometric assay of sPLA.
Topics: Enzyme Activation; Fatty Acids; Fluorescent Dyes; Molecular Structure; Phosphatidylcholines; Phospholipases A2, Secretory
PubMed: 27894770
DOI: 10.1016/j.chemphyslip.2016.11.006 -
Journal of Lipid Research Apr 1989A rapid isocratic method for determining the total phosphatidylcholine and disaturated phosphatidylcholine levels in lung surfactant preparations by high performance...
A rapid isocratic method for determining the total phosphatidylcholine and disaturated phosphatidylcholine levels in lung surfactant preparations by high performance liquid chromatography (HPLC) is described. The analysis was performed on a 3.9 x 300 mm mu-Porasil column with detection by refractive index. The lipids were eluted with a solvent system of chloroform-acetonitrile-methanol-water-85% phosphoric acid 650:650:500:130:2 (v/v/v/v/v). A 4.6 x 30 mm silica guard column was used in place of an injector loop which served as a sample concentrator and purifier. Phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine, and phosphatidylglycerol, all known components of lung surfactants, were eluted from the loop column and were prevented from reaching the analytical column. Sphingomyelin and lysophosphatidylcholine elute later than the phosphatidylcholines on the analytical column. The method was developed so that phosphatidylcholines elute as a single peak regardless of the fatty acid chain length (C12-C20). When the sample was first oxidized with a potassium permanganate-potassium metaperiodate solution, and potentially interfering oxidation products were removed by extraction into a basic aqueous phase, then only the disaturated phosphatidylcholines were analyzed.
Topics: Animals; Cattle; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Colorimetry; Phosphatidylcholines; Phospholipids; Pulmonary Surfactants
PubMed: 2754340
DOI: No ID Found -
Archives of Disease in Childhood Apr 1992The turnover of the artificial surfactant Exosurf after its administration to infants with respiratory distress syndrome was studied. High performance liquid... (Clinical Trial)
Clinical Trial
The turnover of the artificial surfactant Exosurf after its administration to infants with respiratory distress syndrome was studied. High performance liquid chromatography was used to compare the phosphatidylcholine (PC) composition of serial endotracheal tube secretions from three groups of infants. There were 22 infants who received two doses of Exosurf in 24 hours (group 1), 10 infants who received four doses in 36 hours (group 2), and 41 control infants who did not receive Exosurf. Two parameters were studied: (i) dipalmitoylphosphatidylcholine (DPPC), which is present in both Exosurf and endogenous surfactant, expressed as a percentage of total PC (% DPPC) and (ii) the ratio of DPPC to the entirely endogenous palmitoyloleoylphosphatidylcholine (DPPC:POPC ratio). The administration of Exosurf produced changes in endotracheal tube aspirate PC composition that were detectable for over one week. Four doses of Exosurf in 36 hours prolonged the persistence of these changes compared with two doses in 24 hours, but the numbers of infants were small, and should not be over-interpreted. We conclude that after giving two doses of Exosurf, further doses might best be delayed until after two days, and that further clinical evaluation of dosage regimens is required.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Birth Weight; Chromatography, High Pressure Liquid; Drug Combinations; Fatty Alcohols; Gestational Age; Humans; Infant, Newborn; Intubation, Intratracheal; Phosphatidylcholines; Phosphorylcholine; Polyethylene Glycols; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 1586175
DOI: 10.1136/adc.67.4_spec_no.383