Traber M G, Sokol R J, Kohlschütter A, Yokota T, Muller D P, Dufour R, Kayden H J
Department of Medicine, New York University School of Medicine, NY 10016.
J Lipid Res. 1993 Feb;34(2):201-10.
We assessed whether patients with familial isolated vitamin E deficiency could discriminate between natural (RRR-) and synthetic (SRR-) stereoisomers of alpha-tocopherol labeled with six (d6) or three (d3) deuterium atoms, respectively. After oral administration of 20 mg of each of the stereoisomers, patients (seven) and controls (seven) had similar concentrations of both in chylomicrons, similar initial increases of both, and similar rates of decrease of d3-SRR-alpha-tocopherol in plasma. Patients and controls differed in their abilities to maintain plasma d6-RRR-alpha-tocopherol concentrations. Controls maintained plasma d6-RRR-alpha-tocopherol concentrations by preferentially secreting it in very low density lipoprotein (VLDL). Three of seven patients did not discriminate between the two stereoisomers and their plasma and lipoprotein d6-RRR-alpha-tocopherol concentrations declined rapidly. The remaining patients were intermediate between non-discriminators and controls in their ability to discriminate and maintain plasma d6-RRR-alpha-tocopherol concentrations. The degree of discrimination between the two stereoisomers in the patients was correlated with the age of onset of the neurologic disability (r2 = 0.64, P < 0.03). Estimates based on the rate of decrease of plasma d6-RRR-alpha-tocopherol in non-discriminators suggest that the entire plasma alpha-tocopherol pool of normal subjects is replaced daily. We suggest 1) that a hepatic alpha-tocopherol binding protein, which preferentially incorporates RRR-alpha-tocopherol into VLDL, is required to maintain plasma RRR-alpha-tocopherol concentrations; 2) that non-discriminators are lacking this protein, or have a marked defect in the RRR-alpha-tocopherol binding region of the protein; and 3) that patients who discriminate, but have difficulty maintaining plasma RRR-alpha-tocopherol concentrations, have a less severe defect, or perhaps a defect in the transfer function of the protein.
我们评估了患有家族性单纯维生素E缺乏症的患者是否能够区分分别标记有六个（d6）或三个（d3）氘原子的天然（RRR-）和合成（SRR-）立体异构体的α-生育酚。口服给予每种立体异构体20毫克后，患者（7名）和对照组（7名）的乳糜微粒中两者的浓度相似，两者的初始增加相似，血浆中d3-SRR-α-生育酚的下降速率也相似。患者和对照组在维持血浆d6-RRR-α-生育酚浓度的能力上存在差异。对照组通过优先将其分泌到极低密度脂蛋白（VLDL）中来维持血浆d6-RRR-α-生育酚浓度。7名患者中有3名无法区分这两种立体异构体，其血浆和脂蛋白d6-RRR-α-生育酚浓度迅速下降。其余患者在区分和维持血浆d6-RRR-α-生育酚浓度的能力上介于非区分者和对照组之间。患者中两种立体异构体之间的区分程度与神经功能障碍的发病年龄相关（r2 = 0.64，P < 0.03）。根据非区分者血浆d6-RRR-α-生育酚的下降速率进行的估计表明，正常受试者的整个血浆α-生育酚池每天都会更新。我们认为：1）需要一种肝脏α-生育酚结合蛋白，它优先将RRR-α-生育酚掺入VLDL中，以维持血浆RRR-α-生育酚浓度；2）非区分者缺乏这种蛋白，或者在该蛋白的RRR-α-生育酚结合区域存在明显缺陷；3）能够区分但难以维持血浆RRR-α-生育酚浓度的患者，其缺陷较轻，或者可能是该蛋白的转运功能存在缺陷。
