alpha-Tocopheryl phosphate - An active lipid mediator?

The vitamin E (alpha-tocopherol, alpha T) derivative, alpha-tocopheryl phosphate (alpha TP), is detectable in small amounts in plasma, tissues, and cultured cells. Studies done in vitro and in vivo suggest that alpha T can become phosphorylated and alpha TP dephosphorylated, suggesting the existence of enzyme(s) with alpha T kinase or alpha TP phosphatase activity, respectively. As a supplement in animal studies, alpha TP can reach plasma concentrations similar to alpha T and only a part is dephosphorylated; thus, alpha TP may act both as pro-vitamin E, but also as phosphorylated form of vitamin E with possibly novel regulatory activities. Many effects of alpha TP have been described: in the test tube alpha TP modulates the activity of several enzymes; in cell culture alpha TP affects proliferation, apoptosis, signal transduction, and gene expression; in animal studies alpha TP prevents atherosclerosis, ischemia/reperfusion injury, and induces hippocampal long-term potentiation. At the molecular level, alpha TP may act as a cofactor for enzymes, as an active lipid mediator similar to other phosphorylated lipids, or indirectly by altering membrane characteristics such as lipid rafts, fluidity, and curvature. In this review, the molecular and cellular activities of alpha TP are examined and the possible functions of alpha TP as a natural compound, cofactor and active lipid mediator involved in signal transduction and gene expression discussed.