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Molecular Membrane Interactions of a Phospholipid Metabolite. Implications for Alzheimer's Disease Pathophysiology a
Author(s) -
MASON R. P.,
TRUMBORE M. W.,
PETTEGREW J. W.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb34447.x
Subject(s) - phospholipid , chemistry , lipid bilayer , bilayer , liposome , lipid bilayer phase behavior , phosphatidylcholine , biophysics , membrane fluidity , vesicle , cholesterol , membrane , crystallography , biochemistry , biology
Alzheimers's disease is characterized by changes in phospholipid metabolism leading to a perturbation in the levels of phosphomonoesters, including L‐Phosphoserine (L‐PS). These early changes in lipid metabolism may result in a defect in membrane bilayer structure, leading to increased rates of β‐amyloid formation. To investigate the effect of L‐PS on membrane lipid bilayers, small angle x‐ray diffraction and high resolution differential scanning calorimetry (DSC) approaches were used with liposomes composed of lecithin and cholesterol. A one‐dimensional electron density profile of a control dimyristoyl phosphatidylcholine (DMPC)/cholesterol lipid bilayer with a unit cell dimension of 52 Å at 37 0 C was generated from the x‐ray diffraction data. Following incubation with 2.0 mM L‐PS, a broad decrease in electron density ±4‐12Å from the lipid bilayer center was observed concomitant with an increase in the width of the phospholipid headgroup electron density and a 3Å reduction in lipid bilayer width. The interactions of L‐PS with DMPC lipid bilayers were concentrationdependent, highly affected by cholesterol content and reproduced in egg phosphatidylcholine/cholesterol liposomes. DSC analysis showed that millimolar (1.0‐5.0 mM) L‐PS levels decreased the phase transition cooperative unit size of DMPC liposomes in a highly concentration‐dependent manner which was significantly greater in preparations containing 10 mol% cholesterol. These data provide direct evidence that phosphomonoester levels modulate the biophysical properties of the membrane lipid bilayer which may, in turn, lead to altered structure/function relationships in AD.