Leonard Scott W, Paterson Elaine, Atkinson Jeffrey K, Ramakrishnan Rajasekhar, Cross Carroll E, Traber Maret G
Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331, USA.
Free Radic Biol Med. 2005 Apr 1;38(7):857-66. doi: 10.1016/j.freeradbiomed.2004.12.001.
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.
我们推测,人体血浆中α-生育酚和γ-生育酚的浓度反映了它们在动力学方面的差异,尤其是受γ-生育酚代谢的影响。在14名人体受试者中,通过口服等摩尔比的d6-α-生育酚醋酸酯和d2-γ-生育酚醋酸酯各约50mg来评估维生素E的动力学。采用质谱法测量氘代血浆生育酚以及血浆和尿液中的维生素E代谢产物α-和γ-羧乙基羟基色满(CEHC)。血浆d2-γ-生育酚的分数消失率(FDR;1.39±0.44池/天,平均值±标准差)比d6-α-生育酚(0.33±0.11)大三倍多(p<0.001)。d2-γ-生育酚的半衰期为13±4小时,而d6-α-生育酚为57±19小时。血浆和尿液中均未检测到d6-α-CEHC(检测限为1nmol/L),而γ-CEHC(标记的和未标记的)在12小时时从129±20nmol/L增加到258±40nmol/L,并在48小时时恢复到基线水平;在12小时时,d2-γ-CEHC占血浆γ-CEHC的54±4%。与男性相比,女性的d2-γ-生育酚FDR更高(p<0.004),血浆d2-γ-CEHC的最大浓度更高(p<0.02),CEHC的FDR更高(p<0.007),并且尿液中排出的d2-γ-CEHC是男性的四倍(p<0.04)。因此,γ-生育酚迅速代谢为γ-CEHC,且女性的代谢程度高于男性,而α-生育酚则维持在血浆中,很少代谢为α-CEHC。