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Title: α-tocopherol is well designed to protect polyunsaturated phospholipids: MD simulations

Here, the presumptive function for alpha-tocopherol (αtoc) in membranes is to protect polyunsaturated lipids against oxidation. Although the chemistry of the process is well established, the role played by molecular structure that we address here with atomistic molecular-dynamics simulations remains controversial. The simulations were run in the constant particle NPT ensemble on hydrated lipid bilayers composed of SDPC (1-stearoyl-2-docosahexaenoylphosphatidylcholine, 18:0-22:6PC) and SOPC (1-stearoyl-2-oleoylphosphatidylcholine, 18:0-18:1PC) in the presence of 20 mol % αtoc at 37°C. SDPC with SA (stearic acid) for the sn-1 chain and DHA (docosahexaenoic acid) for the sn-2 chain is representative of polyunsaturated phospholipids, while SOPC with OA (oleic acid) substituted for the sn-2 chain serves as a monounsaturated control. Solid-state 2H nuclear magnetic resonance and neutron diffraction experiments provide validation. The simulations demonstrate that high disorder enhances the probability that DHA chains at the sn-2 position in SDPC rise up to the bilayer surface, whereby they encounter the chromanol group on αtoc molecules. This behavior is reflected in the van der Waals energy of interaction between αtoc and acyl chains, and illustrated by density maps of distribution for acyl chains around αtoc molecules that were constructed. An ability to more easily penetrate deep into the bilayer ismore » another attribute conferred upon the chromanol group in αtoc by the high disorder possessed by DHA. By examining the trajectory of single molecules, we found that αtoc flip-flops across the SDPC bilayer on a submicrosecond timescale that is an order-of-magnitude greater than in SOPC. Our results reveal mechanisms by which the sacrificial hydroxyl group on the chromanol group can trap lipid peroxyl radicals within the interior and near the surface of a polyunsaturated membrane. At the same time, water-soluble reducing agents that regenerate αtoc can access the chromanol group when it locates at the surface.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [4] ;  [4] ;  [7] ;  [1]
  1. Indiana Univ.-Purdue Univ. Indianapolis, Indianapolis, IN (United States)
  2. Indiana University-Purdue University Indianapolis (IUPUI)
  3. Brock Univ., St. Catharines, ON (Canada); Univ. of Graz, Graz (Austria)
  4. Brock Univ., St. Catharines, ON (Canada)
  5. Canadian Neutron Beam Centre, Chalk River, ON (Canada); Comenius Univ., Bratislava (Slovakia)
  6. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Joint Institute for Neutron Sciences, Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  7. Wabash College, Crawfordsville, IN (United States)
Publication Date:
Grant/Contract Number:
AC05-00OR22725; DEAC05-00OR2275
Published Article
Journal Name:
Biophysical Journal
Additional Journal Information:
Journal Volume: 109; Journal Issue: 8; Journal ID: ISSN 0006-3495
Research Org:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1259328; OSTI ID: 1267029