Vitamin E: metabolism and molecular aspects

Abstract Vitamin E metabolism is a complex and highly regulated process intimately associated with lipoprotein metabolism. Hepatic steps of this process markedly differ between alpha-tocopherol (α-TOH) and other forms of this vitamin, including the cytochrome P450-dependent transformation to a series of metabolites that are now utilized as both nutritional and functional indicators of the vitamin status and metabolism. In the last three decades a number of protein interactions and gene modulation effects that characterize these differences have identified. These aspects are described in this chapter along with the recently identified role of enzymatic and free radical-derived metabolites of this vitamin as bioactive lipids. Compelling in vitro and in vivo data demonstrate that long-chain metabolites of α-TOH are more potent than their precursor in modulating peroxidation reactions and lipid metabolism, inflammatory genes, cell cycle regulation, and antiatherogenic pathways. The majority of these studies took advantage of the recently developed lipidomics technology allowing unbiased identifications and quantification of the entire spectrum of physiological metabolite in biological fluids, cell culture samples, and tissues. Other achievements also included the recognition of new metabolites, the identity of which are currently under investigation. These studies on the functional metabolome of vitamin E have led to speculation that, similarly to other fat-soluble vitamins, vitamin E may provide some of its biological roles by behaving as a provitamin. If confirmed this would represent a real breakthrough in human nutrition and a major step forward in defining vitamin E essentiality and adequacy, and their assessment strategy as well.