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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sphingolipids make up 30 to 40 mole % of the phospholipids found in the surface membrane of Tetrahymena pyriformis NT-1. We have identified the two major classes as non-hydroxy fatty acid-containing ceramide-2-aminoethylphosphonate (NCAEP) and alpha-hydroxy fatty acid-containing ceramide-2-aminoethylphosphonate (HCAEP). Both classes were well represented in cells grown at 39 degrees C. At this temperature their principal long chain bases were n-hexadeca-4-sphingenine and n-nonadeca-4-sphingenine. The major fatty acid of NCAEP from 39 degrees C-grown cells was palmitic acid and that of HCAEP was alpha-hydroxypalmitic acid. Cells grown at 15 degrees C contained NCAEP, but only traces of HCAEP. By analyzing the incorporation of [1-14C]palmitic acid into cells growing isothermally or shifted from 15 degrees C to 39 degrees C, we obtained evidence favoring a direct conversion of NCAEP to HCAEP. This conversion was blocked in cells grown at 15 degrees C, causing an accumulation of NCAEP. Tetrahymena is a useful model system for studying the poorly understood alpha-hydroxylation process that is of critical importance in myelination of animal nervous tissues.
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PMID:Temperature-induced changes in the hydroxy and non-hydroxy fatty acid-containing sphingolipids abundant in the surface membrane of Tetrahymena pyriformis NT-1. 642 52

Neurospora crassa strain cel, which is deficient in fatty acid synthesis, was grown with phytanic acid supplementation. The temperature dependence of membrane potential is increased by growth on phytanic acid. A temperature change of 40 degrees C produces a change of 184 mV in phytanic acid-grown cells as compared to a 50 mV change for cel grown on palmitic acid or wild-type. Membrane resistance (measured as DC input resistance) of phytanic acid-grown cells did not differ from cel grown on palmitic acid or wild-type. Lipid analysis of cel grown on phytanic acid revealed approximately 7 mole percent phytanic acid incorporation into phospholipids, no change in phospholipid base composition, a reduction of ergosterol content from 80 to 30 percent, and the induction of beta sitosterol, a sterol not usually present in Neurospora. beta sitosterol accounted for approximately 60 percent of the sterol present. Incorporation of 7 mole percent phytanic acid into phospholipids lowers the phase transition temperature by approximately 5 degrees C, and decreases the heat content of the phase transition (delta H) slightly. Results are discussed in relation to Refsum's disease, a human neurological disorder associated with high plasma levels of phytanic acid. It is proposed that high intracellular phytanic acid concentration induces novel sterol synthesis and that the incorporation of the novel sterol into the membrane is responsible for the increased temperature sensitivity of membrane potential. The excitable membrane deficits observed in patients with Refsum's disease may be explained by such a mechanism.
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PMID:Role of lipids in the Neurospora crassa membrane: IV. Biochemical and electrophysiological changes caused by growth on phytanic acid. 646 Jan 6

Mixtures of dipalmitoylphosphatidylcholine (DPPC) with palmitic, stearic, and myristic acids and the sodium salts of these acids were analyzed by differential thermal analysis (DTA) over a wide range of lipid compositions, all in excess water. All three fatty acids raise the liquid-crystal phase transition temperature and form sharp-melting complexes, with 1:2 DPPC--fatty acid stoichiometry observed for palmitic and stearic acids and suggested for myristic acid. Phase diagrams of the peritectic type, indicating nonideal mixing, was fitted to the DPPC--palmitic acid and DPPC--stearic acid data. In contrast, DPPC forms nearly ideal mixtures with the putative DPPC--myristic acid complex. At levels of only a few mole percent, both sodium stearate and myristate remove the pretransition and main transition and produce new peaks at approximately 30 and approximately 48 degrees C; the relative areas of the new peaks were unreproducible for the DPPC--myristate system. Sodium palmitate is the least disruptive of any of the sodium soaps or fatty acids; up to 80 mol % palmitate, the transition is lowered 3 degrees C and approximately doubled in width. The pretransition is detectable up to 36 mol %, and the main transition persists up to 88 mol % palmitate. The apparent pK of palmitic acid (12 mol %) in DPPC bilayers was determined to be 10.2 by direct pH measurement of ternary DPPC mixtures with known palmitic acid/sodium palmitate ratios; the intrinsic pK is estimated to be less than or approximately 8.5.
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PMID:Differential thermal analysis of dipalmitoylphosphatidylcholine--fatty acid mixtures. 689 1

Intracellular fatty acid-binding protein is purified and characterized from aerobic skeletal muscle of the Antarctic icefish Chaenocephalus aceratus. Molecular mass of C. aceratus FABP (CA-FABP) is 14,936 Da as estimated by electrospray mass spectrometry. CA-FABP is expressed at an intracellular concentration of 0.984 +/- 0.115 mg CA-FABP g-1 wet weight aerobic muscle and binds 0.859 +/- 0.013 moles oleic acid per mole of protein at a physiological temperature of 0 degrees C. Dissociation constants (KdS for various fatty acid ligands range from 1.38 to 2.71 microM; KdS are not significantly different among palmitic acid (16:0), palmitoleic acid (16:1), and oleic acid (18:1). Competition assays reveal that CA-FABP does not have preferential affinity for the very-long-chain, polyunsaturated fatty acids that are common in Antarctic fish (e.g., docosahexaenoic acid; 22:6). Partial amino acid sequence from CA-FABP aligns with mammalian heart-type FABPs with as high as 74% identity. These data are strikingly similar to mammalian values, yet they are derived from an organism that is distant from mammals in terms of phylogeny, body temperature, and physiology. This suggests that the FABP family is conserved not only in primary sequence, but also in its physiological properties.
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PMID:Purification and characterization of fatty acid-binding protein from aerobic muscle of the Antarctic icefish Chaenocephalus aceratus. 759 83

Phospholipase A2-catalyzed hydrolysis of phosphatidylcholine large unilamellar vesicles is characterized by a period of slow hydrolysis followed by a rapid increase in the rate of hydrolysis. The temporal relationship between the burst of PLA2 activity and the lateral distribution of substrate and product lipids was examined by simultaneously recording product accumulation and the fluorescence of 1-pyrenyldecanoate, a fatty acid derivative sensitive to lipid distribution and lateral diffusion. The excimer: monomer ratio of the probe changes slowly prior to the burst in activity and then abruptly at the time of the burst. A partial phase diagram for the ternary codispersion of substrate and products (dipalmitoylphosphatidylcholine and 1:1 monopalmitoylphosphatidylcholine/palmitic acid) was constructed by differential scanning calorimetry and suggests gel/gel immiscibility in this system. Thus, the changes in pyrene fluorescence during the time course of hydrolysis appear to be due to lateral phase separation. The critical mole fraction of product both for lateral phase separation in the gel state and for elimination of the lag phase is approximately 0.083. The simultaneous recordings of PLA2 activity and pyrene fluorescence show that the lateral rearrangement of lipids begins prior to and continues during the rapid activation process of PLA2. Two possible effects of lateral phase separation are that concentration of the protein in the product-rich regions promotes putative dimerization or that formation of phase interface regions promotes enzyme activation.
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PMID:Role of lateral phase separation in the modulation of phospholipase A2 activity. 842 69

Low- and wide-angle X-ray diffraction were used to determine the structural organization of lipids isolated from the stratum corneum extracellular matrix that forms the major water permeability barrier in mammalian epidermis. Hydrated pig skin ceramides gave a single low-angle reflection of about 62 angstroms and a wide-angle-reflection at 4.15 angstroms. The addition of either cholesterol or fatty acid, the other major lipid components of the skin stratum corneum extracellular matrix, modified this diffraction pattern, depending on the lipid mole ratios. In the absence of water, lipid mixtures exhibited lipid phase separation, as shown by low- and wide-angle reflections typical of a separate cholesterol phase. However, a hydrated 2:1:1 mole ratio of ceramide:cholesterol:palmitic acid (similar to that found in stratum corneum) produced a diffraction pattern with a single sharp wide-angle reflection at 4.10 angstroms and low-angle reflections which indexed as the first eight orders of a single repeat period of 130 angstroms. The repeat period and intensity distribution of the low-angle data were similar to those found in intact stratum corneum [White et al. (1988) Biochemistry 27, 3725-3732; Bouwstra et al. (1994) Biochim. Biophys. Acta 1212, 183-192]. Higher concentrations of cholesterol or palmitic acid resulted in lipid phase separations. The 130 angstrom repeat period decreased only about 3 angstroms as water was removed by incubation in low-relative humidity atmospheres. The 130 angstrom repeat period depended on the presence of a particular ceramide, N-(omega-acyloxy)-acylsphingosine, which is found only in the epidermis. In contrast, 2:1:1 mixtures of brain ceramide:cholesterol:palmitic acid gave reflections of 56 and 34 angstroms. These results indicate that a structure with dimensions similar to those of the lamellar repeating unit found in skin stratum corneum does not depend on the presence of protein but does depend on the presence of specific skin ceramides and appropriate concentrations of cholesterol and fatty acid.
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PMID:X-ray diffraction analysis of isolated skin lipids: reconstitution of intercellular lipid domains. 861 83

beta-Lactoglobulin (Big) binds 1 mol of a fatty acid spin-label analog, 5-doxylstearic acid (5-DSA), per mole of protein with a dissociation constant Kd = 0.8 microM for the strongest binding site. There are also several weaker sites for this ligand. Blg saturated with either retinol or retinoic acid binds 5-DSA with essentially equal affinity (Kd = 0.6 and 1 microM, respectively). Palmitic acid and SDS displace bound 5-DSA from Blg. However, unlike palmitic acid, 5-DSA binding does not enhance the structural stability of Blg to urea denaturation. The spin-labeled fatty acid also binds to the protein at low pH, presumably at secondary fatty acid binding sites. These results suggest that Blg binds at least two different types of hydrophobic ligands simultaneously.
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PMID:Fatty acids and retinoids bind independently and simultaneously to beta-lactoglobulin. 904 77

Sphingomyelinase activity against pure sphingomyelin monolayers is constant up to a surface pressure of 18 mN/m and falls above it. Sphingomyelinase- and phospholipase A2-mediated phosphohydrolytic pathways are mutually modulated by the presence of their respective substrates and products. At 15 mN/m non-substrate lipids such as ceramide at a mole fraction of 0.1 in mixed films with the pure substrate, inhibit the sphingomyelinase activity. Ganglioside GM1, another ceramide-containing complex sphingolipid, also inhibits sphingomyelinase activity, while a chemically related glycosphingolipid such as asialo-GM1 has no effect. The activity is unaltered by dipalmitoylphosphatidylcholine and by an equimolar mixture of its products of hydrolysis by phospholipase A2, fatty acid and lysoderivative, but it is inhibited by only one of them or by dilauroylphosphatidylcholine. Phospholipase A2 is inhibited by sphingomyelin, and activated by ceramide and by palmitic acid, one of the products of its own phosphohydrolytic reaction.
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PMID:Mutual modulation of sphingomyelinase and phospholipase A2 activities against mixed lipid monolayers by their lipid intermediates and glycosphingolipids. 916 Mar 38

The permeability of mammalian skin is determined in large part by lamellar lipid domains packed between cells of the upper layer of the epidermis, the stratum comeum. Although these lamellae have features in common with typical biological membranes, they differ in having a lipid population composed mainly of ceramides, cholesterol, and free fatty acids. In our initial studies of the relationship between lipid composition and phase behavior in this unusual system, we used deuterium NMR [Kitson et al. (1994) Biochemistry 33, 6707-6715] to examine aqueous dispersions of nonhydroxylated bovine brain ceramide, cholesterol, and perdeuterated palmitic acid, and found complex phase behavior as a function of temperature and pH, whereas analogous dispersions in which sphingomyelin replaced ceramide resulted in spectra consistent with a fluid lamellar phase under the same conditions. To extend these observations, we examined the same dispersions at pH 5.2 by means of X-ray diffraction. The significant findings are as follows: (1) the ceramide dispersions form complex crystalline phases between room temperature and about 40 degrees C; (2) the majority of the crystalline cholesterol is not in a separate phase; and (3) the analogous sphingomyelin dispersions form a fluid lamellar phase under the same conditions. We conclude that ceramides, even in the presence of considerable mole fractions of cholesterol, can form crystalline lamellar structures. We suggest that the existence of such structures in stratum corneum may be important in the function of the epidermal permeability barrier, and that the interaction between ceramide and cholesterol in other biological membranes may result in regions having unique physical properties.
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PMID:A model membrane approach to the epidermal permeability barrier: an X-ray diffraction study. 920 12

The action of phospholipase A2 (PLA2) on bilayer substrates causes the accumulation of reaction products, lyso-phospholipid and fatty acid. These reaction products and the phospholipid substrate generate compositional heterogeneities and then apparently phase separate when a critical mole fraction of reaction product accumulates in the membrane. This putative phase separation drives an abrupt morphologic rearrangement of the vesicle, which may be in turn responsible for modulating the activity of PLA2. Here we examine the thermotropic properties of the phase-separated lipid system formed upon hydrating colyophilized reaction products (1:1 palmitic acid:1-palmitoyl-2-lyso-phosphatidylcholine) and substrate, dipalmitoylphosphatidylcholine. The mixture forms structures which are not canonical spherical vesicles and appear to be disks in the gel-state. The main gel-liquid transition of these structures is hysteretic. This hysteresis is apparent using several techniques, each selected for its sensitivity to different aspects of a lipid aggregate's structure. The thermotropic hysteresis reflects the coupling between phase separation and changes in vesicle morphology.
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PMID:The relationship between compositional phase separation and vesicle morphology: implications for the regulation of phospholipase A2 by membrane structure. 945 Mar 23


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