Regulation of Human Plasma Vitamin E

Abstract

Publisher Summary There is renewed interest in the role of vitamin E in human nutrition because of the demonstration that vitamin E deficiency occurs in humans consuming apparently adequate diets. It has been seen that a neurologic disorder is caused by genetic defects in a liver protein necessary for the incorporation of vitamin E into plasma lipoproteins. The studies leading to this conclusion are highlighted. Information about the plasma transport of vitamin E was gleaned using stable isotopes and gas chromatography/mass spectrometry to analyze lipoprotein fractions. Techniques of molecular biology were instrumental in the isolation of the hepatic tocopherol transport protein and in the identification of genetic defects in this protein, which ultimately causes vitamin E deficiency in humans. These studies now open approaches in investigating the function of vitamin E, which may include more than just antioxidant function. The chapter details vitamin E and low density lipoprotein absorption, chylomicron secretion and catabolism, turnover rates, discrimination between tocopherols, and the tocopherol transfer protein including the genetic defect in the α-tocopherol transfer protein. A kinetic model of plasma vitamin E transport was developed from the results of studies in humans using deuterium-labeled stereoisomers of α-tocopherol. In normal subjects given equimolar amounts of these two labeled stereoisomers, plasma was preferentially enriched in RRR-α-tocopherol within 24 hr. It is explained how although labeled RRR-α-tocopherol apparently leaves the plasma compartment slowly, but the opposite is true. The term vitamin E includes eight naturally occurring molecules: four tocopherols and four tocotrienols. The four forms of tocopherols and tocotrienols differ in the number of methyl groups on the chromanol nucleus. The γ-tocopherol, which has a phytyl tail in the natural conformation, and SRR-α-tocopherol, which has the opposite conformation at the 2-position, has similar plasma disappearance kinetics and disappears from the plasma more rapidly than RRR-α-tocopherol.