α-Tocopherol Is Well Designed to Protect Polyunsaturated Phospholipids: MD Simulations
Abstract
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 »
- Authors:
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1329722
- Alternate Identifier(s):
- OSTI ID: 1259328; OSTI ID: 1267029
- Grant/Contract Number:
- DEAC05-00OR2275; AC05-00OR22725
- Resource Type:
- Published Article
- Journal Name:
- Biophysical Journal
- Additional Journal Information:
- Journal Name: Biophysical Journal Journal Volume: 109 Journal Issue: 8; Journal ID: ISSN 0006-3495
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Leng, Xiaoling, Kinnun, Jacob J., Marquardt, Drew, Ghefli, Mikel, Kučerka, Norbert, Katsaras, John, Atkinson, Jeffrey, Harroun, Thad A., Feller, Scott E., and Wassall, Stephen R. α-Tocopherol Is Well Designed to Protect Polyunsaturated Phospholipids: MD Simulations. United States: N. p., 2015.
Web. doi:10.1016/j.bpj.2015.08.032.
Leng, Xiaoling, Kinnun, Jacob J., Marquardt, Drew, Ghefli, Mikel, Kučerka, Norbert, Katsaras, John, Atkinson, Jeffrey, Harroun, Thad A., Feller, Scott E., & Wassall, Stephen R. α-Tocopherol Is Well Designed to Protect Polyunsaturated Phospholipids: MD Simulations. United States. https://doi.org/10.1016/j.bpj.2015.08.032
Leng, Xiaoling, Kinnun, Jacob J., Marquardt, Drew, Ghefli, Mikel, Kučerka, Norbert, Katsaras, John, Atkinson, Jeffrey, Harroun, Thad A., Feller, Scott E., and Wassall, Stephen R. Thu .
"α-Tocopherol Is Well Designed to Protect Polyunsaturated Phospholipids: MD Simulations". United States. https://doi.org/10.1016/j.bpj.2015.08.032.
@article{osti_1329722,
title = {α-Tocopherol Is Well Designed to Protect Polyunsaturated Phospholipids: MD Simulations},
author = {Leng, Xiaoling and Kinnun, Jacob J. and Marquardt, Drew and Ghefli, Mikel and Kučerka, Norbert and Katsaras, John and Atkinson, Jeffrey and Harroun, Thad A. and Feller, Scott E. and Wassall, Stephen R.},
abstractNote = {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 is 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.},
doi = {10.1016/j.bpj.2015.08.032},
journal = {Biophysical Journal},
number = 8,
volume = 109,
place = {United States},
year = {Thu Oct 01 00:00:00 EDT 2015},
month = {Thu Oct 01 00:00:00 EDT 2015}
}
https://doi.org/10.1016/j.bpj.2015.08.032
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