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At least 1,423 records · Page 79Linked to original sources
PubMed1978

Reactions between peroxidizing lipids and histidyl residue analogues: enhancement of lipid oxidation and browning by 4-methylimidazole.

As a part of our study on the interactions between peroxidizing lipids and the histidyl imidazole side-chain in simple, low-moisture model systems, 4-methylimidazole (4MI) was reacted with methyl linoleate (ML). This analogue was chosen to avoid interference from other functional groups in histidine (free base) or in proteins. Changes in the concentrations of lipid hydroperoxides, carbonyls, 4MI, and brown pigments were followed over a period of 24 days. The results indicate that 4MI exhibits significant prooxidative activity by reducing the induction period as well as by enhancing the formation of brown pigments. These effects are more pronounced at high 4MI/MI molar ratios and under basic pH's. Upon interactions with peroxidizing ML, as much as 44% of initially present 4MI was destroyed by the sixth day of incubation.

Drug Evaluation↗
PubMed1977

Effect of dietary lipids on fatty acid composition of body lipid in rainbow trout (Salmo gairdneri).

Three isocaloric diets were prepared. Diet 1 (Control) contained 22% herring oil. In diets 2 and 3, a third and a half of the herring oil was replaced, respectively, by an animal fat (lard) which contained a high percentage of saturated fatty acids. Each diet was fed to duplicate groups of rainbow trout for 14 wk. The results of the feeding trial indicated that the concentration of the saturated fatty acids in trout body lipid did not increase despite the high concentration of these fatty acids in Diets 2 and 3. Fish growth, feed efficiency, mortality and the level of fatty acids deposited in fish body lipid and phospholipids are discussed.

Animals↗
PubMed1983

Lipid composition and de novo lipid biosynthesis of human palmar fat in Dupuytren's disease.

Seventy-two surgically obtained Dupuytren's disease palmar-fat (DDPF) specimens and 18 location-matched specimens from patients not suffering from this disease (controls) were studied for their total lipid composition and de novo lipogenic activity. Incubation of "DDPF" with 1-[14C]acetate in oxygen produced [14C]palmitate and [14C]stearate in approximately equal yields as those obtained from "controls." No [14C]octanate was formed in any of the palmar-fat preparations. The lipids and fatty acid analysis revealed differences: (a) DDPF specimens were richer in free fatty acids, methyl esters of fatty acids and free-cholesterol than specimens of controls. (b) DDPF specimens contained less phospholipids. (c) DDPF specimens showed a significantly higher content of octanoate and other short-chain fatty acids than specimens of controls. The above findings are not incompatible with the results expected if some mild hypoxia occurred in DDPF; this has been suggested in the statistical correlations observed for this disease and alcoholism with liver involvement.

Adipose Tissue↗
PubMed2006

Membrane binding of a lipidated N-Ras protein studied in lipid monolayers.

The adsorption of doubly lipidated full-length N-Ras protein on 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) monolayers was studied by lateral pressure analysis, grazing incidence X-ray diffraction (GIXD), and specular reflectivity (XR). N-Ras protein adsorbs to the DPPC monolayer (lateral pressure of 20 mN/m) from the subphase thereby increasing the lateral pressure in the monolayer by 4 mN/m. The protein insertion does not alter the tilt angle and structure of the lipid molecules at the air/water interface but influences the electron density profile of the monolayer. Further, electron density differences into the subphase were observed. The Fresnel normalized reflectivity could be reconstructed in the analysis using box models yielding electron density profiles of the DPPC monolayer in the absence and in the presence of N-Ras protein. The electron density profiles of the DPPC monolayer in the presence of Ras showed clear intensity variations in the headgroup/glycerol/upper chain region, the so-called interface region where previous bilayer studies had confirmed Ras binding.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Expression of genes of lipid synthesis and altered lipid composition modulates L-glutamate efflux of Corynebacterium glutamicum.

L-Glutamate is made with Corynebacterium glutamicum on a scale of more than 106 tons/year. Nevertheless, formation of this amino acid is enigmatic and there is very limited molecular information available to unravel the apparently complex conditions leading to L-glutamate efflux. Here, we report the isolation and overexpression of the genes involved in lipid synthesis: acp, fadD 15, cma, cls, pgsA2, cdsA, gpsA, and plsC, and the inactivation of cma and cls. In addition, the consequences for phospholipid content, temperature sensitivity, as well as detergent-independent and detergent-dependent L-glutamate efflux were quantified. An in part strong alteration of the phospholipid composition was achieved; for instance, overexpression offadD15 encoding an acyl-CoA ligase resulted in an increase of phosphatidyl inositol from 12.6 to 30.2%. All strains, except that overexpressing acp (acyl carrier protein), exhibited increased temperature sensitivity, with the strongest sensitivity present upon cls (cardiolipin synthetase) inactivation. As a consequence of the genetically modified lipid synthesis, L-glutamate efflux changed quite dramatically; for instance, overexpression of plsC (acylglycerolacyl transferase) resulted in a detergent-triggered increase of L-glutamate accumulation from 92 mM to 108 mM, whereas acp overexpression reduced the accumulation to 24 mM. With some of the overexpressed genes, substantial L-glutamate excretion even without detergent addition was obtained when the fermentation temperature was elevated. These data show that the chemical and physical properties of the cytoplasmic membrane are altered and suggest that this is a necessary precondition to achieve L-glutamate efflux.

Bacterial Proteins↗
PubMed1991

Effects of doxazosin on serum lipids: a review of the clinical data and molecular basis for altered lipid metabolism.

The goal of antihypertensive treatment must be not only the reduction of high blood pressure, but also the effective management of elevated cholesterol levels and other risk factors of coronary heart disease (CHD). In controlled clinical trials, doxazosin has been shown to have antihypertensive efficacy comparable with other classes of antihypertensive agents and to lower the levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides while increasing the levels of high-density lipoprotein cholesterol. Doxazosin appears to inhibit the development of CHD on two fronts. First, doxazosin binds to the alpha 1-adrenoreceptor and inhibits the receptor-mediated responses to epinephrine and norepinephrine. Second, doxazosin has direct and indirect effects on lipid metabolism by increasing LDL receptor activity, decreasing intracellular LDL synthesis, reducing the synthesis and secretion of very low-density lipoprotein cholesterol, and stimulating lipoprotein lipase activity. Doxazosin may also inhibit platelet aggregation. Long-term studies will determine how these actions translate into reductions in the morbidity and mortality rates of CHD. First-year results from the Treatment of Mild Hypertension Study (TOMHS) have demonstrated expected reductions in blood pressure for all antihypertensive agents studied. The lipid changes have varied with the type of antihypertensive treatment and have been favorable for doxazosin.

Antihypertensive Agents↗
PubMed1995

Microsomal glutathione transferase: lipid-derived substrates and lipid dependence.

Rat liver microsomal glutathione transferase was found to display glutathione peroxidase activity toward a variety of oxidized lipids. 1-Linoleoyl-2-palmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylethanolamine hydroperoxide, and cholesteryl linoleate hydroperoxide all served as substrates (0.02, 0.04, 0.02, and 0.02 mumol/min mg, respectively). The phospholipid hydroperoxide glutathione peroxidase activity of the enzyme was found not to require detergent and increased when liposomes containing peroxidized phospholipid were fused with liposomes containing microsomal glutathione transferase. Methyl linoleate ozonide serves as a very efficient substrate for the microsomal glutathione transferase. The unactivated and N-ethylmaleimide-activated enzyme displayed specific activities of 0.74 and 5.9 mumol/min mg, respectively. Upon examination of a series of 4-hydroxyalk-2-enals it was found that the catalytic efficiency of the enzyme increases from the 4-hydroxyhept-2-enal up to the 4-hydroxytetradec-2-enal. The specific activities with the various 4-hydroxyalk-2-enals tested varied between 0.28 and 0.95 mumol/min mg. The phospholipid dependence of the microsomal glutathione transferase was examined in proteoliposomes formed by cholate dialysis. Phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine, and rat liver microsomal phospholipids could all be used successfully to reconstitute the enzyme. In conclusion, microsomal glutathione transferase can detoxify a number of lipid peroxidation products as well as a fatty acid ozonide. The results imply a protective role for the enzyme under conditions of oxidative stress.

Animals↗
PubMed1980

Age-dependent modifications in membrane lipids: lipid composition, fluidity and palmitoyl-CoA desaturase in Tetrahymena membranes.

The membrane lipid composition of Tetrahymena pyriformis NT-I was observed to change in a manner markedly dependent on the progress of culture age. The pellicular, mitochondrial and microsomal membranes were isolated from cell harvested at various growth phases (I, early exponential; II, mid-exponential; III, late exponential; IV, early stationary; V, late stationary) and their lipid composition was analyzed by thin-layer and gas-liquid chromatography. Although the phospholipid composition varied somewhat among membrane fractions, the most general age-dependent alteration was a considerable decrease in the content of phosphatidylethanolamine accompanied by a small increase in phosphatidylcholine. The 2-aminoethylphosphonolipid, enriched in the surface membrane pellicle, did not undergo a consistent change. As for fatty acid composition the most notable variation occurred in unsaturated fatty acids; a great increase in oleic and linoleic acids and a compensatory decrease in palmitoleic acid. This resulted in an augmented unsaturation of the overall phospholipid fatty acid profile of the aged membranes. The age-associated drastic decline in the palmitoleic acid content in membrane phospholipids could be accounted for by the markedly lowered activity of palmitoyl-CoA desaturase. The microsomes from the early exponential phase cells possess a 4-fold higher activity of the desaturase as compared to that of the late stationary phase microsomes. The decreased desaturase activity associated with the culture age was also reflected in the corresponding decrease in the conversion rate of [14C]palmitate to [14C]palmitoleate in cells labelled in vivo. The ESR spectra of the spin-labeled phospholipids extracted from the pellicular and microsomal membranes have led to the suggestion that these types of membrane would become more fluid with the age of growth.

Animals↗
PubMed1988

Passive ion permeability of lipid membranes modelled via lipid-domain interfacial area.

A microscopic interaction model of the gel-to-fluid chain-melting phase transition of fully hydrated lipid bilayer membranes is used as a basis for modelling the temperature dependence of passive transmembrane permeability of small ions, e.g. Na+. Computer simulation of the model shows that the phase transition is accompanied by strong lateral density fluctuations which manifest themselves in the formation of inhomogeneous equilibrium structures of coexisting gel and fluid domains. The interfaces of these domains are found to be dominated by intermediate lipid-chain conformations. The interfacial area is shown to have a pronounced peak at the phase transition. By imposing a simple model for ion diffusion through membranes which assigns a high relative permeation rate to the domain interfaces, the interfacial area is then identified as a membrane property which has the proper temperature variation to account for the peculiar experimental observation of a strongly enhanced passive ion permeability at the phase transition. The excellent agreement with the experimental data for Na+-permeation, taken together with recent experimental results for the phase transition kinetics, provides new insight into the microphysical mechanisms of reversible electric breakdown. This insight indicates that there is no need for aqueous pore-formation to explain the experimental observation of a dramatic increase in ion conductance subsequent to electric pulses.

Algorithms↗
PubMed1990

The effect of lipid composition on the relaxivity of Gd-DTPA entrapped in lipid vesicles of defined size.

The effects of lipid composition on the relaxivity of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) entrapped in lipid vesicles has been examined for vesicles of different sizes composed of egg phosphatidylcholine and cholesterol in various molar ratios, as well as the stability of those same vesicles in human serum at 37 degrees C. It is found that the incorporation of cholesterol decreases the apparent relaxivity of the entrapped Gd-DTPA, concomitant with an increase in vesicle stability in serum. Cholesterol has little effect on relaxivity when incorporated at ratios up to 20 mole percent, but has an increasing effect at higher mole percentages. These results correlate with the known effects of cholesterol on the osmotic water permeability coefficients of various model membrane systems and suggest that it is the water flux across the vesicle bilayer that is limiting to the T1 relaxivity of the entrapped Gd-DTPA. The incorporation of up to 20 mole percent cholesterol has little effect on the stability of the vesicles in serum, whereas vesicles containing more than 20 mole percent cholesterol show greater increases in stability. It was also found that the stability of vesicles depends upon the size of the vesicles; smaller vesicles are less stable in human serum at 37 degrees C than larger vesicles.

Blood↗
PubMed1990

Structure of polymerizable lipid bilayers: water profile of a diacetylenic lipid bilayer using elastic neutron scattering.

Elastic neutron scattering experiments have been used to study the hydration of multibilayers of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC). Previously published FTIR spectroscopic data had suggested, based on shifts in the carbonyl (C = O) stretch frequencies, that the phosphocholine headgroup in these polymerizable lipid bilayers was much less hydrated than that of saturated phosphatidylcholines. Our results demonstrate that the DC8,9PC headgroup is at least as well hydrated as that of dipalmitoylphosphatidylcholine (DPPC), a saturated lipid, under the same conditions.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

The cationic lipid stearylamine reduces the permeability of the cationic drugs verapamil and prochlorperazine to lipid bilayers: implications for drug delivery.

The therapeutic activity of a wide variety of drugs is significantly improved when their longevity in the circulation is extended by encapsulation in liposomes. To improve the retention of cationic drugs in liposomes, we have investigated the effect of the cationic lipid stearylamine on the permeability of the calcium channel blocker verapamil and the antipsychotic drug prochlorperazine, both of which are also multidrug resistance modulators. Both drugs were efficiently incorporated into liposomes composed of DSPC/cholesterol that possessed a transmembrane pH gradient (inside acidic). However, the efflux of the loaded drugs was relatively rapid (i.e., 50% of the encapsulated verapamil was released after 4 h at 37 degrees C), despite the presence of a 3 unit pH gradient (pHi = 4.0, pHo = 7.5). Drug retention within the liposomes was improved by increasing the magnitude of the transmembrane pH gradient to approx. 5 units (pHi = 2.0, pHo = 7.5). Further improvements in drug retention were achieved by the addition of 10 mol% of the cationic lipid stearylamine in the DSPC/cholesterol liposomes. The combination of the 5 unit pH gradient and stearylamine resulted in increases of the retention of verapamil and prochlorperazine by approx. 20- and 5-fold, respectively. Calculation of the permeability coefficients for the charged (cationic) and neutral forms of the drugs indicated that the neutral forms of both drugs were approx. 10(4)-fold more permeable than were the cationic forms of the drugs. Further, the presence of stearylamine reduced the permeability coefficient for the cationic species of the drugs by approximately an order of magnitude, but had no effect on the neutral species of the drugs. The efflux curves observed for both verapamil and prochlorperazine could be mathematically modeled by assuming that the primary influence of stearylamine was on the development of a positive surface charge density on the inner monolayer of the liposome. Taken in sum, these results indicate that stearylamine is effective at decreasing the leakage of cationic drugs from liposomes, and may prove to be a valuable component of liposomal drug formulations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Converting an alcohol to an amine in a cationic lipid dramatically alters the co-lipid requirement, cellular transfection activity and the ultrastructure of DNA-cytofectin complexes.

Cytofectins are positively charged lipophilic molecules that readily form complexes with DNA and other anionic polynucleotides. Normally, cytofectins are combined with an activity-augmenting phospholipid such as dioleoylphosphatidylethanolamine (DOPE), and a film of dried, mixed lipid is prepared and hydrated to form cationic liposomes. The liposome solution is then mixed with a plasmid DNA solution to afford cytofectin-DNA complexes which, when presented to living cells, are internalized and the transgene is expressed. One of the most potent cytofectins, dimyristoyl Rosenthal inhibitor ether (DMRIE), is presently being used to deliver transcriptionally active DNA into human tumor tissues. Here we report the remarkable consequences of replacing the alcohol moiety of DMRIE with a primary amine. The resulting cytofectin, called beta-aminoethyl-DMRIE (betaAE-DMRIE), promoted high level transfection over a broad range of DNA and cationic lipid concentrations. A comparison of in vitro transfection activity between DMRIE and betaAE-DMRIE in 10 cell types revealed that betaAE-DMRIE was more active than DMRIE, and that betaAE-DMRIE, unlike DMRIE, was maximally effective in the absence of colipid. The consequences of the alcohol-to-amine conversion on the structure of the cytofectin/DNA complex was also examined by Atomic Force Microscopy. Strikingly dissimilar images were found for plasmid DNA alone and for the plasmid complexes of betaAE-DMRIE and DMRIE/DOPE.

Alcohols↗
PubMed1977

Rate equations and simulation curves for enzymatic reactions which utilize lipids as substrates. I. Interaction of enzymes with the monomers and micelles of soluble, amphiphilic lipids.

Theoretical aspects of the kinetics of interaction of enzymes with lipid substrates are presented. Rate equations were written and used to simulate v versus S curves for interaction of enzymes with "monomers" (i.e. a molecular solution) or micelles (aggregated form) of the "soluble", amphiphilic lipids. The rate equations were written assuming separate kinetic parameters for the interaction of the enzyme with these two forms. Although the rate equations are based on the kinetic theory of Michaelis and Menten, most of the simulated v vs. S curves were not hyperbolic. A procedure is suggested for determining the kinetic parameters with the aid of a graphic method.

Colloids↗
PubMed1990

Effect of lipid composition on the transfer of sterols mediated by non-specific lipid transfer protein (sterol carrier protein2).

The rate of non-specific lipid transfer protein (nsLTP)-mediated exchange is independent of structure for dissimilar sterols: cholesterol, lanosterol, sitosterol and vitamin D-3. Conversely, the nsLTP-mediated exchange of cholesterol is markedly affected by the phospholipid composition of the donor liposome. Negatively charged phosphatidylglycerols strikingly increase cholesterol exchange in the presence of nsLTP while not altering the exchange in the absence of nsLTP. The presence of unsaturated acyl chains in the phospholipid enhances exchange. Sphingomyelin drastically decreases cholesterol exchange, as does di-O-alkylphosphatidylcholine. Decreased exchange produced by these substitutions can be reversed by addition of phosphatidylcholine. The presence of an acyl group and a negative charge in the phospholipid are critical for the nsLTP-mediated transfer of cholesterol. In addition to these studies on composition of the donor membrane, the charge on the membrane also appears critical. Maximal exchange rates accompany optimization of potential interaction of negatively charged surface and the basic nsLTP. The nsLTP also mediates an approximately equal rate of exchange of cholesterol and phosphatidylcholine. However, approaching equilibrium, only half of the phospholipid can be exchanged while there is exchange of about 90% of cholesterol. Thus, it appears that only the phospholipid in an outer membrane layer may be available whereas cholesterol is fully available. Therefore, in contrast to a 'carrier' model we suggest that nsLTP facilitates exchange by binding to the membranes, and binding is highly dependent upon lipid composition. Once bound, the protein functions as a bridge between membranes, thus, facilitating exchange.

Biological Transport↗
PubMed1991

Differential patterns of lipid-protein association in fast and slow cholesterol nucleating human gallbladder biles: implications for cholesterol nucleation from biliary lipid carriers.

We compared the protein/lipid structure and Ch-nucleating capacity of individual lipid carriers in two groups of human gallbladder biles: 11 with Fast cholesterol nucleation (2.2 +/- 1.3 days) and 10 with Slow cholesterol nucleation (19.2 +/- 4.4 days). The groups had comparable cholesterol-saturation (1.31 vs. 1.28), total lipids (9.9 vs. 8.5 g/dl) and proteins (8.5 vs. 7.6 mg/ml). Bile was ultracentrifuged (2 h at 150,000 x g) and the resulting isotropic phase was incubated with [3H]Ch and [14C]lecithin and gel-chromatographed on a Superose 6 column with a buffer containing 7.0 mM sodium-taurocholate. Seven protein peaks were identified (280 nm and biochemistry), with the following molecular mass ranges (kDa): 1 (Void volume), 2 (155-205), 3 (50-79), 4 (20-29), 5 (6-15), 6 (3.5-6), 7 (2-3.5). Peaks 2 and 3 were identified as vesicles and micelles, respectively. Fast vs. Slow Ch nucleating biles had: (a) more (P less than 0.02) cholesterol coeluting with vesicles, (b) more (P less than 0.01) lecithin coeluting with low m.w. peaks (Nos. 5-6), (c) less (P less than 0.01) cholesterol and lecithin coeluting with micelles. An inverse correlation (P less than 0.001) was observed between the amount of proteins coeluting with the micellar peak and the cholesterol nucleation of both whole bile and isolated micellar fractions. A marked shift of cholesterol and lecithin from micelles to vesicles was apparent, in the whole bile, after cholesterol nucleation had occurred. Incubation and sequential analysis of isolated and radiolabeled micelles showed a progressive transfer of lecithin and cholesterol molecules to low molecular weight fractions and to vesicles before cholesterol nucleation. We conclude that pro-nucleating biliary vesicles develop from micelles, due to the phasing out and redistribution of micellar cholesterol and lecithin, which are probably induced by biliary proteins.

Adult↗
PubMed1983

Lipid bilayer dynamics and rhodopsin-lipid interactions: new approach using high-resolution solid-state 13C NMR.

High-resolution, solid-state 13C NMR spectra have been obtained for unsonicated multilamellar dispersions of 1,2-dilauryl-sn-glycero-3-phosphocholine (DLPC), recombinant membranes containing DLPC and rhodopsin, and native retinal rod disk membranes. The roles of 1H dipolar decoupling, 1H-13C cross-polarization, and magic-angle sample spinning have been investigated. Rotating-frame 13C relaxation times have been measured and are discussed in terms of lipid bilayer dynamics and rhodopsin-lipid interactions.

Fatty Acids, Unsaturated↗
PubMed1993

Nucleotide and negatively charged lipid-dependent vesicle aggregation caused by SecA. Evidence that SecA contains two lipid-binding sites.

SecA which is an overall acidic protein was found to induce an increase in the turbidity of a solution of vesicles consisting of negatively charged phospholipids. This increase was found to be due to an aggregation of the vesicles mediated by SecA. The SecA-mediated vesicle aggregation was not found for zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine and showed a large dependence on both temperature and ionic strength. Furthermore it was shown that ATP and to a lesser extent ADP+Pi were able to reduce the SecA-mediated vesicle aggregation, while no effect could be seen for a non-hydrolysable ATP analog AMP-PNP. Using the steady state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene present in 1,2-dioleoyl-sn-glycero-3-phosphoglycerol vesicles we could show that SecA inserts in the bilayer. Monolayer studies confirmed that SecA is able to cause close contact between two membranes and gave a direct insight into the different types of lipid-protein interactions involved. From our results we propose that the SecA monomer possesses two lipid-binding sites which in the functional dimer conformation are responsible for the SecA-mediated vesicle aggregation.

Adenosine Triphosphatases↗