Deuterium NMR study of the interaction of .alpha.-tocopherol with a phospholipid model membrane

Wassall, Stephen R.; Thewalt, Jenifer; Wong, Linda; Gorrissen, Heiner; Cushley, Robert J.

doi:10.1021/bi00350a006

Cited by 90 publications

(40 citation statements)

References 31 publications

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“…The detergents and lipids are represented as sticks, the van der Waals surface are indicated as shadow and the hydrogen acceptors (oxygens) are in red. contrast to an increase in the acyl chain ordering by 17% [50]. Membrane ordering/disordering effects are generally observed at much higher concentrations than used to inhibit P-gp [51].…”

Section: The Influence Of Detergents On the Lateral Packing Density Omentioning

confidence: 99%

Enhancement of drug absorption by noncharged detergents through membrane and P-glycoprotein binding

Seelig

Gerebtzoff

2006

Expert Opinion on Drug Metabolism & Toxicology

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Noncharged detergents are used as excipients in drug formulations. Until recently, they were considered as inert compounds, enhancing drug absorption essentially by improving drug solubility. However, many detergents insert into lipid membranes, although to different extents, and change the lateral packing density of membranes at high concentrations. Moreover, they bind to the efflux transporter P-glycoprotein (P-gp) and most likely to related transporters and metabolising enzymes with overlapping substrate specificities. If their affinity to P-gp is higher than that of the coadministered drug they act as modulators or inhibitors of P-gp and enhance drug absorption. Inhibition of P-gp and related proteins can, however, cause severe side effects. This paper first reviews the membrane binding propensity of different noncharged detergents (including poloxamers) and discusses their ability to bind to P-gp. Second, literature data on drug uptake enhancement by noncharged detergents, obtained in vivo and in vitro, are analysed at the molecular level. The present analysis provides the tools for an approximate and simple prior estimate of the membrane and P-gp binding ability of noncharged detergents based on a modular binding approach.

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Section: The Influence Of Detergents On the Lateral Packing Density Omentioning

confidence: 99%

Enhancement of drug absorption by noncharged detergents through membrane and P-glycoprotein binding

Seelig

Gerebtzoff

2006

Expert Opinion on Drug Metabolism & Toxicology

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“…Structurally, all four tocopherols (a-, b-, g-, and d-tocopherols) consist of a chromanol head group attached to a phytyl tail and differ only in the number and positions of methyl groups on the chromanol ring ( Figure 1). Tocopherols are amphipathic molecules, and in vitro studies using artificial membranes have shown that tocopherols form complexes with specific lipid constituents and physically stabilize membranes (Wassall et al, 1986;Stillwell et al, 1996;Wang and Quinn, 2000;Bradford et al, 2003). Tocopherols can efficiently quench singlet oxygen, scavenge various radicals, particularly lipid peroxy radicals, and thereby terminate lipid peroxidation chain reactions (Liebler and Burr, 1992;Bramley et al, 2000;Schneider, 2005).…”

Section: Introductionmentioning

confidence: 99%

Tocopherols Play a Crucial Role in Low-Temperature Adaptation and Phloem Loading in Arabidopsis

et al. 2006

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To test whether tocopherols (vitamin E) are essential in the protection against oxidative stress in plants, a series of Arabidopsis thaliana vitamin E (vte) biosynthetic mutants that accumulate different types and levels of tocopherols and pathway intermediates were analyzed under abiotic stress. Surprisingly subtle differences were observed between the tocopheroldeficient vte2 mutant and the wild type during high-light, salinity, and drought stresses. However, vte2, and to a lesser extent vte1, exhibited dramatic phenotypes under low temperature (i.e., increased anthocyanin levels and reduced growth and seed production). That these changes were independent of light level and occurred in the absence of photoinhibition or lipid peroxidation suggests that the mechanisms involved are independent of tocopherol functions in photoprotection. Compared with the wild type, vte1 and vte2 had reduced rates of photoassimilate export as early as 6 h into low-temperature treatment, increased soluble sugar levels by 60 h, and increased starch and reduced photosynthetic electron transport rate by 14 d. The rapid reduction in photoassimilate export in vte2 coincides with callose deposition exclusively in phloem parenchyma transfer cell walls adjacent to the companion cell/sieve element complex. Together, these results indicate that tocopherols have a more limited role in photoprotection than previously assumed but play crucial roles in low-temperature adaptation and phloem loading.

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“…has concentrated on changes in the structure and permeability of the membrane. Usually mixed liposomes with phosphatidylcholine were used, and a variety of techniques were applied: differential scanning calorimetry (Cushley et al, 1979;Massey et al, 1982;Lai et al, 1985), I3C and 31P nuclear magnetic resonance (NMR)' (Cushley & Forrest, 1977), and recently 2 H N M R of deuteriated fatty acids in lipids (Wassall et al, 1986). It was found that a-tocopherol broadens and lowers slightly the temperature of the gel-liquid-crystal phase transition, increases ordering of lipids above the phase transition, and changes the permeability of model membranes.…”

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confidence: 99%

Structure and dynamics of .alpha.-tocopherol in model membranes and in solution: a broad-line and high-resolution NMR study

Ekiel

Hughes²,

Burton³

et al. 1988

Biochemistry

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Nuclear magnetic resonance has been applied to study the conformational dynamics of alpha-tocopherol (vitamin E) in solution and in model membranes. In nonviscous solution, 1H nuclear magnetic resonance (NMR) showed that alpha-tocopherol is in rapid equilibrium between two or more puckered conformers of its heterocyclic ring. The most likely conformers to be so involved are the two half-chair forms. Deuterium NMR spectra of specifically deuteriated alpha-tocopherol in multilamellar dispersions of egg phosphatidylcholine, measured in the liquid-crystalline state, were characteristic of axially symmetric motional averaging. The orientation of the rotational axis within the molecular framework was determined. Studies on oriented multilamellar membranes revealed that this axis is perpendicular to the surface of the membrane. The profile of quadrupolar splittings along the hydrophobic tail does not have a plateau, in contrast to that of the fatty acyl chains of the membrane lipids. Longitudinal relaxation times (T1) were short. The presence of a minimum in their temperature dependence shows that molecular motion with an effective correlation time tau eff approximately equal to 3 X 10(-9)s is responsible for relaxation. However, the temperatures and absolute values of the minima depend on the position of the deuterium in the molecule, demonstrating that tau eff represents a complex blend of motions.

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Deuterium NMR study of the interaction of .alpha.-tocopherol with a phospholipid model membrane

Cited by 90 publications

References 31 publications

Enhancement of drug absorption by noncharged detergents through membrane and P-glycoprotein binding

Enhancement of drug absorption by noncharged detergents through membrane and P-glycoprotein binding

Tocopherols Play a Crucial Role in Low-Temperature Adaptation and Phloem Loading in Arabidopsis

Structure and dynamics of .alpha.-tocopherol in model membranes and in solution: a broad-line and high-resolution NMR study

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