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The physical presence of vitamin E in lipid membranes

Mitchell DiPasquale, Michael H.L. Nguyen, Brett W. Rickeard, and Drew Marquardt Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada Since its discovery over 90 years ago, the biological significance of vitamin E (tocopherol) has been surrounded by controversy.1,2 Physiologically, Vitamin E deficiency has been correlated to several health disorders yet clear molecular mechanisms for many these phenotypes remain elusive.3,4 Numerous studies have found -tocopherol, the predominant species of vitamin E, to be an antioxidant in vitro, often interpreting the biomolecules function to be fat-soluble peroxyl radical scavenger,5 however, others have directly opposed this theory.6 The antioxidant theory is supported by studies by Marquardt et al, in which neutron diffraction reveals the transverse membrane orientation of -tocopherol to be appropriate for interception of reactive oxygen species as well as to terminate lipid-borne radicals.7 Studies have since diverged to show that -tocopherol may in fact have vital roles in cellular processes such as signaling, apoptosis, protein activity, and gene regulation.4,6,8 Considering the lack of conclusive investigations, the absence of a clear antioxidant health benefit from supplementation, and its significantly low physiological concentrations, skepticism builds regarding the true biological function of vitamin E. It is known to localize in lipid membranes, and so investigations on the physical effect produced by tocopherol are vital, yet absent. Preliminary experiments employing gas chromatography and densitometry suggested that -tocopherol favours localization in less ordered environments, such as those provided by unsaturated lipids. In the context of biological membrane systems, cholesterol is vital in the maintenance of membrane integrity by promoting lipid organization into phases of liquid-ordered (Lo) and liquiddisordered (Ld) domains, which allow for the formation of functional lipid rafts.9 The latter of these phases is favourable for tocopherol localization.