Biomedical subjects
Jeffrey K Atkinson
Publications and source records attributed to Jeffrey K Atkinson.
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.