Vitamin E trafficking

The alpha-tocopherol transfer protein (alpha-TTP) is required to prevent vitamin E deficiency in humans and in alpha-TTP null mice. Whereas alpha-TTP is not required to facilitate intestinal absorption of vitamin E, it is required to maintain normal alpha-tocopherol concentrations in plasma and extrahepatic tissues. alpha-Tocopherol secretion from the liver in very low density lipoproteins (VLDLs) is impaired in humans with a defect in the alpha-TTP gene. In perfusions of isolated cynomolgus monkey livers, VLDLs were preferentially enriched in RRR-alpha-tocopherol. The mechanism by which alpha-TTP incorporates alpha-tocopherol into nascent VLDLs is the topic of this report. VLDL assembly is a multistep secretory process that occurs within the membrane compartments of the endoplasmic reticulum and Golgi apparatus. Thus, we postulated that alpha-TTP might transfer alpha-tocopherol onto nascent VLDLs either in the endoplasmic reticulum or in the Golgi apparatus. To test these possibilities, we isolated nascent VLDLs from highly purified RER and Golgi apparatus membrane fractions from livers of rats fed equimolar ratios of RRR- and SRR-alpha-tocopherols labeled with different amounts of deuterium. Although the plasma was enriched i...Continue Reading