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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The topological distribution of phospholipids between the inside and the outside of rabbit kidney brush-border membranes has been investigated by incubating membrane vesicles with sphingomyelinase, phospholipases A2 from bee venom and hog pancreas, phospholipases C and D, and trinitrobenzene sulfonate. Orientation and integrity of vesicles upon phospholipase treatment was determined by using two monoclonal antibodies recognizing an extracytoplasmic and a cytoplasmic domain, respectively, of the neutral endopeptidase (EC 3.4.24.11). It is shown that the transbilayer distribution of phospholipids is highly asymmetrical in kidney brush-border membranes: sphingomyelin accounted for 75% of the phospholipids present in the external leaflet, whereas phosphatidylethanolamine and phosphatidylserine plus phosphatidylinositol were found to comprise the majority of the inner layer of the membrane.
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PMID:Phospholipid asymmetry in renal brush-border membranes. 316 18

The phospholipid distribution across red cell membrane bilayer is asymmetrical. Sphingomyelin and phosphatidylcholine are predominantly present in the outer membrane bilayer, whereas only small amounts of phosphatidylethanolamine and no phosphatidylserine are present in the outer membrane bilayer. The present study, using specific phospholipase, chemical probe, and Russell's viper venom clotting time has found that in neonatal red cells a portion of PS is also present in the outer membrane bilayer.
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PMID:Presence of phosphatidylserine in the outer membrane bilayer of newborn human erythrocytes. 371 3

Phospholipid distribution across erythrocyte membrane bilayer is asymmetrical. In normal erythrocytes, entire phosphatidylserine (PS) and most of the phosphatidylethanolamine (PE) is present on the cytoplasmic side of membrane bilayer, whereas phosphatidylcholine (PC) and sphingomyelin (SM) are predominantly present at the outer side of membrane bilayer. The present study was undertaken to determine whether membrane lipid peroxidation has any effect on the distribution of PS, PE, and PC across erythrocyte membrane bilayer in vivo in an animal model. Erythrocyte membrane lipid peroxidation was induced in rats by administering phenylhydrazine, an oxidant drug. Membrane phospholipid organization was determined by using bee venom phospholipase-A2 and indirectly by measuring clotting time on recalcification of normal human platelet-poor plasma in the presence of Russell's viper venom. Phenylhydrazine administration to rats caused significant membrane lipid peroxidation as measured by the accumulation of malonyldialdehyde (MDA), an end product of fatty acid peroxidation, as well as externalization of a significant portion of PS and PE from the inner to the outer side of membrane bilayer in erythrocytes. There was a significant positive correlation (r) between the amount of MDA accumulated in the erythrocytes and the movement of PS (r = 0.92) and PE (r = 0.96) from inner to the outer membrane bilayer and PC (r = 0.81) from outer to the inner membrane bilayer. Erythrocytes of phenylhydrazine-treated rats also showed significantly reduced clotting time. This reduction in clotting time had a significant positive correlation with MDA accumulation (r = 0.92) and PS externalization (r = 0.90). Both the effect of phenylhydrazine on erythrocyte membrane lipid peroxidation and alterations in phospholipid organization and coagulability were blocked when rats were simultaneously administered with vitamin E or C antioxidants.
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PMID:In vivo externalization of phosphatidylserine and phosphatidylethanolamine in the membrane bilayer and hypercoagulability by the lipid peroxidation of erythrocytes in rats. 401 80

Reaction progress curves for the hydrolysis of dimyristoylphosphatidylcholine by pig pancreatic phospholipase A2 exhibits a latency phase. Addition of 1-palmitoyllysophosphatidylcholine to the preformed vesicles reduces the latency phase and enhances the binding of phospholipase A2 to the vesicles. In contrast, the binary codispersions prepared from diacylphospholipids premixed with lysophosphatidylcholine do not exhibit such enhanced susceptibility to the phospholipase. This effect appears to be due to organizational defects created by asymmetrical incorporation of lysophospholipid molecules into the outer monolayer of the vesicles, and the action of phospholipase is not observed when the additive is equilibrated in both the monolayers of the vesicles.
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PMID:Activation of phospholipase A2 by freshly added lysophospholipids. 665 80

The phospholipids distribution across red cell membrane bilayer is asymmetrical. Phosphatidylcholine (PC) and sphingomyelin (SM) are predominantly present in the outer, and phosphatidylserine (PS) and phosphatidylethanolamine (PE) are predominantly present on the cytoplasmic side of the red cell membrane. The present study reports the effect of fatty acid peroxidation on the organization of PS and PE in human red cells using a nonpermeable Bee Venom phospholipase-A2 which specifically hydrolyzes outer bilayer lipids. Lipid peroxidation in the red cell membranes was accomplished by exposing cells to hydrogen peroxide. This treatment resulted in a significant movement of PS and PE from inner bilayer to outer bilayer, which had a highly positive correlation with the concentration of malonyldialdehyde generated in the red cells. Antioxidant vitamin E abolished the effects of peroxide treatment on fatty acid peroxidation and red cell membrane lipid organization. Thus, lipid peroxidative damage can disturb organization of phospholipids in the membrane bilayer of human red cells.
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PMID:Vitamin E and stabilization of membrane lipid organization in red blood cells with peroxidative damage. 667 17

The distribution of the three major phospholipids of bovine rod outer segment disk membranes over the two faces of the membrane has been studied by means of treatment with phospholipase C, phospholipase A2 and phospholipase D. Two different preparations of rod outer segment disk membranes have been used, which are called 'stacked disks' and 'disk vesicles' on account of their morphological appearance. The hydrolysis patterns obtained by phospholipase treatment of these preparations have been compared to those of a retinal lipid suspension or detergent-solubilized disk membranes, which serve as control preparations with a similar phospholipid composition but a random availability of the phospholipids. Special attention is given to the early phase of enzyme treatment in order to eliminate secondary effects on the molecular organization of the membrane due to appreciable phospholipid hydrolysis. Analysis of the hydrolysis patterns for all three phospholipases in stacked disks, as compared to those in randomized control preparations, suggests a slightly asymmetrical distribution of phosphatidylcholine (40--45% at the outer face) and phosphatidylethanolamine (55--60% at the outer face) and a symmetrical distribution of phosphatidylserine in rod outer segment disk membranes. Extensive treatment with phospholipases C and A2 leads ultimately to nearly complete hydrolysis of all phospholipids, but with phospholipase D a final level of 40% phospholipid hydrolysis is observed in stacked disk preparations. This suggests that in the latter case the inner face of the membrane is inaccessible to the enzyme. Further work will be necessary in order to substantiate these conclusions.
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PMID:Transbilayer distribution of phospholipids in photoreceptor membrane studied with various phospholipases. 744 82

Src homology 3 (SH3) and WW domains are known to associate with proline-rich motifs within their respective ligands. Here we demonstrate that the proposed adapter protein for Src kinases, Sam68, is a ligand whose proline-rich motifs interact with the SH3 domains of p59(fyn) and phospholipase Cgamma-1 as well as with the WW domains of FBP30 and FBP21. These proline-rich motifs, in turn, are flanked by RG repeats that represent targets for the type I protein arginine N-methyltransferase. The asymmetrical dimethylation of arginine residues within these RG repeats dramatically reduces the binding of the SH3 domains of p59(fyn) and phospholipase Cgamma-1, but has no effect on their binding to the WW domain of FBP30. These results suggest that protein arginine methylation can selectively modulate certain protein-protein interactions and that mechanisms exist for the irreversible regulation of SH3 domain-mediated interactions.
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PMID:Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains. 1074 27

The outer membrane (OM) bilayer of Gram-negative bacteria is biologically unique in its asymmetrical organization of lipids, with an inner leaflet composed of glycerophospholipids (PLs) and a surface-exposed outer leaflet composed of lipopolysaccharide (LPS). This lipid organization is integral to the OM's barrier properties. Perturbations of the outer leaflet by antimicrobial peptides or defects in LPS biosynthesis or transport to the OM cause a compensatory flipping of PLs to the outer leaflet. As a result, lipid asymmetry is disrupted and OM integrity is compromised. Recently, we identified an Escherichia coli mutant that exhibits aberrant accumulation of surface PLs accompanied by a cellular increase in LPS production. Remarkably, the observed hyperproduction of LPS is PldA dependent. Here we provide evidence that the fatty acids generated by PldA at the OM are transported into the cytoplasm and simultaneously activated by thioesterification to coenzyme A (CoA) by FadD. The acyl-CoAs produced ultimately inhibit LpxC degradation by FtsH. The increased levels of LpxC, the enzyme that catalyzes the first committed step in LPS biosynthesis, increases the amount of LPS produced. Our data suggest that PldA acts as a sensor for lipid asymmetry in the OM. PldA protects the OM barrier by both degrading mislocalized PLs and generating lipid second messengers that enable long-distance signaling that prompts the cell to restore homeostasis at a distant organelle.IMPORTANCE The outer membrane of Gram-negative bacteria is an effective permeability barrier that protects the cell from toxic agents, including antibiotics. Barrier defects are often manifested by phospholipids present in the outer leaflet of this membrane that take up space normally occupied by lipopolysaccharide. We have discovered a signaling mechanism that operates across the entire cell envelope used by the cell to detect these outer membrane defects. A phospholipase, PldA, that functions to degrade these mislocalized phospholipids has a second, equally important function as a sensor. The fatty acids produced by hydrolysis of the phospholipids act as second messengers to signal the cell that more lipopolysaccharide is needed. These fatty acids diffuse across the periplasm and are transported into the cytoplasm by a process that attaches coenzyme A. The acyl-CoA molecule produces signals to inhibit the degradation of the critical enzyme LpxC by the ATP-dependent protease FtsH, increasing lipopolysaccharide production.
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PMID:The Escherichia coli Phospholipase PldA Regulates Outer Membrane Homeostasis via Lipid Signaling. 2971 14