Impaired ability of patients with familial isolated vitamin E deficiency to incorporate α-tocopherol into lipoproteins secreted by the liver

Department of Medicine, New York University School of Medicine, New York 10016.
Journal of Clinical Investigation (Impact Factor: 13.22). 03/1990; 85(2):397-407. DOI: 10.1172/JCI114452
Source: PubMed


Plasma and lipoprotein alpha-tocopherol concentrations of four patients with familial isolated vitamin E deficiency and six control subjects were observed for 4 d after an oral dose (approximately 15 mg) of RRR-alpha-tocopheryl acetate labeled with six deuterium atoms (d6-tocopherol). Chylomicron d6-tocopherol concentrations were similar in the two groups. d6-Tocopherol concentrations of plasma, very low (VLDL), low (LDL), and high (HDL) density lipoproteins were similar in the two groups only during the first 12 h; then these were significantly lower, and the rate of disappearance faster, in the patients. The times (tmax) of the maximum chylomicron d6-tocopherol concentrations were similar for the two groups, but tmax values in the controls increased in the order: chylomicrons less than VLDL less than or equal to LDL approximately HDL, while the corresponding values in the patients were similar to the chylomicron tmax. Thus, plasma d6-tocopherol in controls increased during chylomicron and VLDL catabolism, whereas in patients it increased only during chylomicron catabolism, thereby resulting in a premature and faster decline in the plasma tocopherol concentration due to a lack of d6-tocopherol secretion from the liver. We suggest that these patients are lacking or have a defective liver "tocopherol binding protein" that incorporates alpha-tocopherol into nascent VLDL.

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    • "Familial isolated deficiency of vitamin E (VED; MIM 277460) is a recessive disorder caused by mutations in the gene encoding α-tocopherol transfer protein, TTPA (Ouahchi et al. 1995). Deficiency of this protein prohibits α-tocopherols, members of the vitamin E family of molecules, from being incorporated into plasma VLDL (Traber et al. 1990) and results in vitamin E deficiency and resultant neurological symptoms—most strikingly a Friedreich-like ataxia (Harding et al. 1985). Vitamin E supplementation slows progression of the disease or may even lead to some improvement of neurological symptoms (Gabsi et al. 2001; Mariotti et al. 2004). "
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    • "In this study, knockout mice fed with normal diet of vitamin E did not show early after infection stressing that one of the reasons of inhibition of parasite proliferation in the knockout mice is clearly related to oxidative damage of the parasite. This suggests that knockout mice might possess additional mechanisms to keep normal levels of vitamin E in the RBC membranes [30]. It is impressive that α-TTP knockout mice survived with rising levels of parasitaemia at the later stage of the infection. "
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