Sex differences in the inhibition of gamma-tocopherol metabolism by a single dose of dietary sesame oil in healthy subjects.

BACKGROUND: Gamma-tocopherol has unique properties that may be beneficial in sustaining optimal human health, but hepatic vitamin E metabolism enhances gamma-tocopherol turnover. OBJECTIVE: Our aim was to determine the extent to which dietary sesame lignans alter human alpha- and gamma-tocopherol metabolism and elimination as carboxyethyl hydroxychromanols (CEHCs). DESIGN: Healthy participants (n = 5 women and 5 men) in a randomized, crossover study (with 4-wk washout) consumed muffins prepared with either corn oil or unrefined sesame oil (sesamin, 94 mg; sesamolin, 42 mg), along with a capsule containing a 1:1 molar ratio of deuterium-labeled d(6)-alpha- and d(2)-gamma-tocopherol acetates ( approximately 50 mg each). Plasma and urine were collected up to 72 h; unlabeled and labeled tocopherol and CEHC concentrations were determined by liquid chromatography-mass spectrometry. RESULTS: Sesame oil muffin consumption in men, but not in women, decreased (P < 0.05) areas under plasma d(2)-gamma-CEHC concentration-time curves (area under the curve) and maximum concentrations. However, in both sexes urinary d(2)-gamma-CEHCs were decreased for 24 h following sesame oil muffin consumption. CONCLUSIONS: In humans, gamma-tocopherol metabolism can be inhibited by the simultaneous consumption of gamma-tocopherol and sesame lignans. The observed differences between men and women with respect to vitamin E metabolism warrant further investigation.

Specific lipids supply critical negative spontaneous curvature--an essential component of native Ca2+-triggered membrane fusion.

The Ca(2+)-triggered merger of two apposed membranes is the defining step of regulated exocytosis. CHOL is required at critical levels in secretory vesicle membranes to enable efficient, native membrane fusion: CHOL-sphingomyelin enriched microdomains organize the site and regulate fusion efficiency, and CHOL directly supports the capacity for membrane merger by virtue of its negative spontaneous curvature. Specific, structurally dissimilar lipids substitute for CHOL in supporting the ability of vesicles to fuse: diacylglycerol, alphaT, and phosphatidylethanolamine support triggered fusion in CHOL-depleted vesicles, and this correlates quantitatively with the amount of curvature each imparts to the membrane. Lipids of lesser negative curvature than cholesterol do not support fusion. The fundamental mechanism of regulated bilayer merger requires not only a defined amount of membrane-negative curvature, but this curvature must be provided by molecules having a specific, critical spontaneous curvature. Such a local lipid composition is energetically favorable, ensuring the necessary "spontaneous" lipid rearrangements that must occur during native membrane fusion-Ca(2+)-triggered fusion pore formation and expansion. Thus, different fusion sites or vesicle types can use specific alternate lipidic components, or combinations thereof, to facilitate and modulate the fusion pore.

Studies in humans using deuterium-labeled alpha- and gamma-tocopherols demonstrate faster plasma gamma-tocopherol disappearance and greater gamma-metabolite production.

We hypothesized that human plasma alpha- and gamma-tocopherol concentrations reflect differences in their kinetics, especially influenced by gamma-tocopherol metabolism. Vitamin E kinetics were evaluated in humans (n=14) using approximately 50 mg each of an equimolar ratio of d6-alpha- and d2-gamma-tocopheryl acetates administered orally. Mass spectrometry was used to measure deuterated plasma tocopherols, as well as plasma and urinary vitamin E metabolites, alpha- and gamma-carboxyethylhydroxychromans (CEHCs). Plasma d2-gamma-tocopherol fractional disappearance rates (FDR; 1.39+/-0.44 pools/day, mean+/-SD) were more than three times greater than those of d6-alpha-tocopherol (0.33+/-0.11, p<0.001). The d2-gamma-tocopherol half-life was 13+/-4 h compared with 57+/-19 for d6-alpha-tocopherol. Whereas neither plasma nor urinary d6-alpha-CEHC was detectable (limit of detection 1 nmol/L), gamma-CEHC (labeled plus unlabeled) increased from 129+/-20 to 258+/-40 nmol/L by 12 h and returned to baseline by 48 h; at 12 h d2-gamma-CEHC represented 54+/-4% of plasma gamma-CEHC. Women compared with men had a greater d2-gamma-tocopherol FDR (p<0.004) and a greater maximal plasma d2-gamma-CEHC concentration (p<0.02) and CEHC FDR (p<0.007), as well as excreting four times as much d2-gamma-CEHC (p<0.04) in urine. Thus, gamma-tocopherol is rapidly metabolized to gamma-CEHC, and to a greater degree in women than in men, whereas alpha-tocopherol is maintained in the plasma and little is metabolized to alpha-CEHC.

Fluorescent tocopherols as probes of inter-vesicular transfer catalyzed by the alpha-tocopherol transfer protein.

Novel fluorescent analogues of alpha-tocopherol have been prepared that incorporate the useful fluorophores nitrobenoxadiazyl (NBD) and anthroyloxy (AO). Both fluorescent tocopherol analogues bind specifically to recombinant human tocopherol transfer protein (hTTP). The NBD-alpha-tocopherol is particularly useful for protein-binding assays, whereas the AO-alpha-tocopherol was designed to be one of a pair of chromophores for a fluorescence resonance energy transfer (FRET) assay of intervesicular tocopherol transfer. It is now possible to follow AO-alpha-tocopherol transfer from donor lipid vesicles composed of predominantly phosphatidylcholine (PC) to acceptor lipid vesicles containing PC and a quenching lipid NBD-PE (2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[7-nitro-2-1,3-benzoxadiazol-4-yl]). The presence of hTTP substantially increases the rate of AO-alpha-tocopherol transfer over the uncatalyzed spontaneous rate.