Vitamin E Promotes the Inverse Hexagonal Phase via a Novel Mechanism: Implications for Antioxidant Role

Abstract

Vitamin E (α-tocopherol) and a range of other biological compounds have long been known to promote the H II (inverted hexagonal) phase in lipids. Now, it has been well established that purely hydrophobic lipids such as dodecane promote the H II phase by relieving extensive packing stress. They do so by residing deep within the hydrocarbon core. However, we argue from X-ray diffraction data obtained with 1-palmitoyl-2-oleoylphosphatidylcholine (POPE) and 1,2-dioleoylphosphatidylcholine (DOPE) that α-tocopherol promotes the H II phase by a different mechanism. The OH group on the chromanol moiety of α-tocopherol anchors it near the aqueous interface. This restriction combined with the relatively short length of α-tocopherol (compared to DOPE and POPE), means that α-tocopherol promotes the H II phase by relieving compressive packing stress. This observation offers new insight into the nature of packing stress and lipid biophysics. With the deeper understanding of packing stress offered by our results, we also explore the role molecular structure plays in the primary function of vitamin E, which is to prevent the oxidation of polyunsaturated membrane lipids.

Mechanistic Insight into How PEGylation Reduces the Efficacy of pH-Sensitive Liposomes from Molecular Dynamics Simulations

“… 80 Finally, vitamin E (α-tocopherol) promotes formation of the hexagonal phase by an alternative, more complex mechanism. 81 …”

“…Also, low hydration is a factor promoting the formation of hexagonal phases . Finally, vitamin E (α-tocopherol) promotes formation of the hexagonal phase by an alternative, more complex mechanism …”

Lipid monolayer spontaneous curvatures: A collection of published values

“…OA, EA, DD, HD, retinal and retinoic acid which all show tight negative curvatures [23]. Many of these compounds, notably αToc (vitamin E) [65] are of importance in oxidative stress/ lipid peroxidation pathways [38]. Ceramide lipids also show negative c 0 values and as anticipated increasing the second alkyl chain length decreases c 0 [56].…”

Does membrane curvature elastic energy play a role in mediating oxidative stress in lipid membranes?

“…Vitamin E and other tocopherols have been widely shown to prevent oxidative damage [2,79,145,175,176], and whilst it is very clear that Vitamin E has an antioxidant effect, via a radical quenching mechanism [5], a significant number of studies have established that it has a negative spontaneous curvature (circa -0.75 nm -1 ) and significant effects on the physical properties of lipid membranes [167,177].…”