Water-Soluble Vitamin E—Tocopheryl Phosphate

Vitamin E: Regulatory role in the cardiovascular system

“…Beside side chain oxidation, the phosphorylated form of α‐tocopherol, known as α‐TP, might be more active and unique than α‐tocopherol in regulating cellular events, including proliferation, survival/apoptosis, enzyme translocation, and lipid transport, due to its similarity to phosphorylated messenger lipids and ability to modulate protein‐membrane interactions . THP‐1 monocytes that are deficient in hydrolyzing α‐TP have been widely used in earlier studies.…”

“…The emerging function of alpha longchain metabolites, especially α-13 0 -carboxychromanol, was also observed in the suppression of acute inflammation as well as bronchial hyper-reactivity via accumulating at the sites of inflammation followed by the inhibition of 5-lipoxygenase and the production of 5-lipoxygenase-derived lipid mediators (99). Beside side chain oxidation, the phosphorylated form of α-tocopherol, known as α-TP, might be more active and unique than α-tocopherol in regulating cellular events, including proliferation, survival/apoptosis, enzyme translocation, and lipid transport, due to its similarity to phosphorylated messenger lipids and ability to modulate protein-membrane interactions (100,101). THP-1 monocytes that are deficient in hydrolyzing α-TP have been widely used in earlier studies.…”

Vitamin E: Regulatory Role on Signal Transduction

“…Differential competition between lipids and the eight vitamin E analogues at the active site of lipid metabolic enzymes such as phospholipase A2 (PLA2), 5‐, 12‐, and 15‐lipoxygenases (5‐, 12‐, and 15‐LOX, respectively), cyclooxygenase‐2 (COX‐2), and 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase modulates the production of specific messenger lipids such as the inflammatory lipid mediator leukotriene B(4) . Moreover, vitamin E is metabolized and converted into a number of active lipid mediators (e.g., α‐tocopheryl phosphate (αTP), carboxyethylhydroxychromans (CEHC) and long‐chain CEHC precursors, α‐tocopherol quinone/hydroquinone (αTQ/αTHQ), α‐tocopheryl nicotinate) that can have increased and/or additional activities when compared to the non‐converted precursors . In some cases, regulatory effects similar to vitamin E are also mediated by PUFA‐derived lipid mediators, that are protected by vitamin E from oxidation and destruction , thus indirectly contributing to the prevention of diseases in which PUFA are beneficial such as cancer, insulin resistance, inflammation, NASH, and cardiovascular and neurodegenerative diseases .…”

“…These regulatory effects on vitamin E on mechanisms relevant for its own cellular uptake, secretion and metabolism may also affect the ones of other lipids, including cholesterol, free and essential fatty acids (FFA, MUFA, and PUFA) and their derived lipid mediators able to influence cell signaling and gene expression. In monocytes and macrophages and vascular smooth muscle cells (VSMC), vitamin E may limit the cellular levels of these lipids and of excess vitamin E by reducing the levels of scavenger receptors CD36 and SR‐BI via down‐regulation of expression and surface exposition . In some cases, the eight vitamin E analogues and their metabolites may affect the synthesis of PUFA‐derived lipid mediators (e.g., prostaglandins, thromboxanes, leukotrienes, eicosanoids, resolvins, lipoxins, neuroprotectins, and others) by competing with PUFA for binding to the enzymes involved, such as desaturases, elongases, P450 epoxygenases, lipoxygenases, and cyclooxygenases .…”

“…The supplementation with vitamin E not only increases LDL αT content and increases LDL resistance to oxidation, but also decreases the cytotoxicity of oxLDL to cultured vascular endothelial cells by down‐regulating CD36 and increasing PPARγ, LXRα, and ABCA1 expression . Moreover, CD36 gene expression and cell surface exposition is inhibited by αT and more strongly by αTP involving most likely binding to CD36 and triggering its internalization by not yet completely resolved signaling mechanisms involving regulatory effects on PKC, PI3K, and PKB .…”