Non-antioxidant activities of vitamin E.
Molecules in biological systems often can perform more than one function. In particular, many molecules have the ability to chemically scavenge free radicals and thus act in the test tube as antioxidant, but their main biological function is by acting as hormones, ligands for transcription factors, modulators of enzymatic activities or as structural components. In fact, oxidation of these molecules may impair their biological function, and cellular defense systems exist which protect these molecules from oxidation. Vitamin E is present in plants in 8 different forms with more or less equal antioxidant potential (alpha-, beta-, gamma-, delta-tocopherol/tocotrienols); nevertheless, in higher organisms only alpha-tocopherol is preferentially retained suggesting a specific mechanism for the uptake for this analogue. In the last 20 years, the route of tocopherol from the diet into the body has been clarified and the proteins involved in the uptake and selective retention of alpha-tocopherol discovered. Precise cellular functions of alpha-tocopherol that are independent of its antioxidant/radical scavenging ability have been characterized in recent years. At the posttranslational level, alpha-tocopherol inhibits protein kinase C, 5-lipoxygenase and phospholipase A2 and activates protein phosphatase 2A and diacylglycerol kinase. Some genes (e. g. scavenger receptors, alpha-TTP, alpha-tropomyosin, matrix metalloproteinase-19 and collagenase) are modulated by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also inhibits cell proliferation, platelet aggregation and monocyte adhesion. These effects are unrelated to the antioxidant activity of vitamin E, and possibly reflect specific interactions of alpha-tocopherol with enzymes, structural proteins, lipids and transcription factors. Recently, several novel tocopherol binding proteins have been cloned, that may mediate the non-antioxidant signaling and cellular functions of vitamin E and its correct intracellular distribution. In the present review, it is suggested that the non-antioxidant activities of tocopherols represent the main biological reason for the selective retention of alpha-tocopherol in the body, or vice versa, for the metabolic conversion and consequent elimination of the other tocopherols.
Zingg
Jean-Marc
JM
Institute of Biochemistry and Molecular Biology, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland. zingg@mci.unibe.ch
Azzi
Angelo
A
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D019587:Dietary Supplements; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008099:Liver / Q000378:metabolism; D011315:Preventive Medicine; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014810:Vitamin E / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*; D024502:alpha-Tocopherol / Q000493:pharmacokinetics
D000975:Antioxidants; D002352:Carrier Proteins; D004042:Dietary Fats, Unsaturated; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E; D024502:alpha-Tocopherol