title: The location and behavior of alpha-tocopherol in membranes.
abstract: Vitamin E (alpha-tocopherol) has long been recognized as the major antioxidant in biological membranes, and yet many structurally related questions persist of how the vitamin functions. For example, the very low levels of alpha-tocopherol reported for whole cell extracts question how this molecule can successfully protect the comparatively enormous quantities of PUFA-containing phospholipids found in membranes that are highly susceptible to oxidative attack. The contemporary realization that membranes laterally segregate into regions of distinct lipid composition (domains), we propose, provides the answer. We hypothesize alpha-tocopherol partitions into domains that are enriched in polyunsaturated phospholipids, amplifying the concentration of the vitamin in the place where it is most needed. These highly disordered domains depleted in cholesterol are analogous, but organizationally antithetical, to the well-studied lipid rafts. We review here the ideas that led to our hypothesis. Experimental evidence in support of the formation of PUFA-rich domains in model membranes is presented, focusing upon docosahexaenoic acid that is the most unsaturated fatty acid commonly found. Physical methodologies are then described to elucidate the nature of the interaction of alpha-tocopherol with PUFA and to establish that the vitamin and PUFA-containing phospholipids co-localize in non-raft domains.
authors.affiliation: Department of Chemistry, Brock University, St. Catharines, Ont., Canada. jatkin@brocku.ca
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Atkinson
authors.forename: Thad
authors.initials: T
authors.lastname: Harroun
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wassall
authors.forename: William
authors.initials: W
authors.lastname: Stillwell
authors.forename: John
authors.initials: J
authors.lastname: Katsaras
mesh_terms: D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007536:Isomerism; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D014810:Vitamin E / Q000097:blood / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000032:analysis / Q000097:blood / Q000378:metabolism*
chemical_list: D026563:LDL-Receptor Related Protein-Associated Protein; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; D014810:Vitamin E; D024502:alpha-Tocopherol