Molecular and Cellular Activities of Vitamin E Analogues

Abstract

Natural vitamin E comprises 8 different analogues, the alpha-, beta-, gamma-, and delta-tocopherols and the alpha-, beta-, gamma-, and delta-tocotrienols. However, only alpha-tocopherol is selectively enriched by the liver; the other vitamin E analogues and also excess alpha-tocopherol are converted to several metabolites and eliminated. Recently, a novel phosphorylated form of tocopherol, alpha-tocopheryl phosphate, was shown to occur naturally in animal and human tissues as well as in foods. Several synthetic vitamin E derivatives have been synthesized that are either converted by esterases to the natural form, or exert novel or vitamin E related biological activities. During the last years, specific cellular effects for each individual vitamin E analogue have been described that are the consequence of modulating signal transduction and gene expression. These effects possibly reflect specific interactions of each of the vitamin E analogues with enzymes, structural proteins, lipids and transcription factors. In this review, the different natural vitamin E analogues and synthetic derivatives are compiled in relation to their major molecular and cellular activities.

Vitamin E Alters Inflammatory Gene Expression in Alcoholic Chronic Pancreatitis

“…Equally to this work, Schlosser et al [8] also found an increased expression of COX-2 in patients with ACP. Vitamin E can inhibit the catalytic activity of COX-2 in the synthesis of prostaglandins (E2), reducing platelet aggregation and the inflammatory process [16,43]. …”

Present trends in vitamin E research

“…a-and c-carboxyethyl-6-hydroxychromans (CEHC) and long chain metabolites Liver uptake and blood transfer of a-tocopherol are less effective than in the case of a-tocotrienol and c-tocopherol, which have been extensively demonstrated to be the most potent in vitro and in vivo modulators of cell signaling and gene expression [27][28][29]. Tocotrienols have been repeatedly reported to be more effective than a-tocopherol as neuroprotective, hypocholesterolemic, and anticancer agents [30] and further support to the importance of minor tocopherol forms is coming from the clinical side, where supplementation with c-tocopherol alone or in combination with a-tocopherol, but not a-tocopherol alone, was found to improve antioxidant and anti-inflammatory parameters of patients with metabolic syndrome [31].…”

“…Moreover, a recent series of studies has demonstrated the existence of a phosphorylation pathway for the main forms of vitamin E (reviewed in [39] and more recently in [28]). This pathway may serve to activate vitamin E and might represent a biochemical event, analogous to other signaling molecules, at the basis of the biological effects of this vitamin at the cellular level.…”

“…A-tocopherol reaches peripheral tissues thanks to transport mechanisms common to other lipoprotein-associated lipids (reviewed in [28,43]). Similarly to other fat soluble micronutrients such as carotenoids, its concentrations in plasma are clearly under the control of genetic factors; this results in different phenotypes in terms of tocopherol plasma concentrations and response to dietary supplements [44,45].…”

“…Cardiovascular disease (CVD), following the original work of Fred Gey [74,75] showing a geodistribution of this ailment that inversely correlated with the vitamin E intake of the studied populations, has been the object of a large series of in vitro and in vivo studies that initially suggested a role of this vitamin in the prevention of early atherosclerotic lesions (recently reviewed in [10] and [37]) and in the regulation of immuno-inflammatory, coagulative and cell protection mechanisms (reviewed in [28]). Observational evidence of a role of vitamin E in the primary prevention of CVD came mostly from prospective cohorts such as the Nurses' Health Study and the Health Professionals' Follow-Up Study (reviewed in [76]).…”