Tocopherols and tocotrienols. A molecular dynamics study

Vitamin E denotes a cluster of eight molecules, i.e., α-tocopherol, β-tocopherol, δ-tocopherol, γ-tocopherol, α-tocotrienol, β-tocotrienol, δ-tocotrienol and γ-tocotrienol, where the α-tocopherol isoform is the major form. Vitamin E is one of the natural most potent antioxidants and an indispensable molecule for human health, since its major function is the inhibition of free-radical lipid peroxidation propagation. Vitamin E has a lipophilic nature and localize in membranes and lipoproteins and could affect either both its biological properties or membrane structure. I have used molecular dynamics to know the position and orientation of these eight biomolecules in water and inside a biomembrane, besides finding any interactions with their lipidic components. When they are in the membrane, all molecules tend towards their most extended conformation, inserting well between the phospholipid hydrocarbon chains. Our data agree with the general consensus, i.e., the chromanol group is located near the oxygen atom of cholesterol, whereas its hydrophobic chain extends to the membrane middle. This does not prevent the existence of flip-flop between the two monolayers. Significantly, the tocopherol/tocotrienol molecules inside the membrane did not aggregate. Remarkable, α-tocopherol presented a relatively high diffusion coefficient when compared to the other molecules and the α-tocopherol transfer protein seems to be the most suitable for its transport and transfer to the membrane. Although in principle any tocopherol or tocotrienol could function as an antioxidant, nature has chosen α-tocopherol thanks to the sum of a series of very subtle characteristics.