The studies on the metabolic role of vitamin E will continue to focus on evaluation of patients at risk for the neurologic consequences of vitamin E deficiency. The incorporation of tocopherol into lipoproteins will be studied using deuterated forms of naturally occurring tocopherols and different stereoisomers of alpha tocopherol. These studies will be carried out in normal subjects, in patients with genetically defined disorders of lipid metabolism and in the genetic disorder, familial isolated vitamin E deficiency. The regulation of lipoprotein transport of tocopherol will be investigated with particular emphasis upon the documentation of a hepatic tocopherol transfer protein in humans and non-human primates. The tocopherol transfer protein appears to function to discriminate between alpha-tocopherol and gamma-tocopherol and between different isomers of alpha-tocopherol, and the selectivity is expressed via the incorporation of the preferred form, 2'R, 4'R, 8""""""""R-alpha-tocopherol, into the nascent very low density lipoprotein particles. Studies will be carried out to validate this hypothesis. In the genetic disorder, familial isolated vitamin E deficiency, the presumption is that the hepatic tocopherol transfer protein is absent or dysfunctional, and we shall study this possibility. The widespread use of total parenteral nutrition and intravenous lipid emulsions warrants the examination of the role of tocopherol in the protection of the fatty acids of the intravenous lipids. This will be studied both in vivo following infusions of triglyceride-rich lipid emulsions and in incubations with plasma lipoproteins in vitro. The mode of transfer of tocopherol from human plasma into the brain and cerebrospinal fluid will be studied in vitamin E deficient dogs and in humans. These studies will provide new information on the mechanism for discrimination between tocopherols in vivo and will provide new insights into the metabolism of tocopherols.
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