Browsing by Author "Harper, Paul E."

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    An Investigation of Whether Vitamin E Preferentially Interacts with Polyunsaturated Lipids
    (Office of the Vice Chancellor for Research, 2015-04-17) Cavazos, Andres; Kinnun, Jacob J.; Williams, Justin A.; Bank, Morris; Ray, Bruce D.; Harper, Paul E.
    Vitamin E (α-tocopherol) is a lipid-soluble antioxidant that has the role of protecting phospholipids from oxidation in membranes. A question that remains is how the low concentration of α-tocopherol found in whole cells can protect the relatively large concentration of polyunsaturated phospholipids found in membranes that are particularly vulnerable to oxidative attack. We hypothesize that α-tocopherol colocalizes with polyunsaturated phospholipids to optimize its role as an antioxidant. This project attempts to test this hypothesis by comparing the effect of α-tocopherol on the molecular organization of 1-palmitoyl-2-docosahexaenoyl-sn-glycerophosphatidylethanolamine (16:0-22:6PE, PDPE) and, as a monounsaturated control, 1-palmitoyl-2-oleoyl-sn-glycerophosphatidylethanolamine (16:0-18:1PE, POPE) in mixtures with sphingomyelin (SM). By solid-state 2H NMR spectroscopy, we directly observe order and phase behavior of POPE-d31 and PDPE-d31 (analogs of POPE and PDPE with a perdeuterated sn-1 chain) in the mixed membranes. In complementary X-ray diffraction and differential scanning calorimetry experiments we further probe phase behavior. The spectra observed for POPE-d31 in POPE/SM/α-tocopherol (2:2:1 mol) reveal that a transition from gel to liquid crystalline phase is no longer apparent. At higher temperatures there is a superposition of two spectral components that we ascribe to α-tocopherol promoting a transition from lamellar to inverted hexagonal (HII) phase. Analysis of depaked spectra shows that order is increased by about 8 % and that the amount of HII phase increases with temperature, ranging from 7 (31 °C) to 41 % (65 °C). In mixed membranes where POPE-d31 is replaced by PDPE-d31, we shall investigate whether there is a greater tendency for α-tocopherol to increase order and destabilize bilayer structure for the polyunsaturated phospholipid.
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    Vitamin E Promotes the Inverse Hexagonal Phase via a Novel Mechanism: Implications for Antioxidant Role
    (ACS, 2020-05) Harper, Paul E.; Cavazos, Andres T.; Kinnun, Jacob J.; Petrache, Horia I.; Wassall, Stephen R.; Physics, School of Science
    Vitamin E (α-tocopherol) and a range of other biological compounds have long been known to promote the HII (inverted hexagonal) phase in lipids. Now, it has been well established that purely hydrophobic lipids such as dodecane promote the HII 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 HII 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 (as compared to DOPE and POPE) means that α-tocopherol promotes the HII 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 that molecular structure plays in the primary function of vitamin E, which is to prevent the oxidation of polyunsaturated membrane lipids.