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•Human vitamin E deficiency was recognized in the 1950s.•Deficiency symptoms include anemia and peripheral neuropathy.•Vitamin E is defined as 2R-alpha-tocopherols (RRR-, RSR-, RRS-, ...RSS-).•2R-alpha-tocopherols are preferentially retained by the body.•2S-alpha-tocopherols (SRR-, SSR-, SRS-, SSS-) are catabolized and excreted.
The mechanistic properties of two dietary antioxidants that are required by humans, vitamins C and E, are discussed relative to their biological effects. Vitamin C (ascorbic acid) is an essential ...cofactor for α-ketoglutarate-dependent dioxygenases. Examples are prolyl hydroxylases, which play a role in the biosynthesis of collagen and in down-regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism, and neutrophil function and apoptosis. Vitamin C-dependent inhibition of the HIF pathway may provide alternative or additional approaches for controlling tumor progression, infections, and inflammation. Vitamin E (α-tocopherol) functions as an essential lipid-soluble antioxidant, scavenging hydroperoxyl radicals in a lipid milieu. Human symptoms of vitamin E deficiency suggest that its antioxidant properties play a major role in protecting erythrocyte membranes and nervous tissues. As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, by vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products. These bioactivities bear relevance to inflammatory disorders. Vitamin C also plays a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation. Evidence from plants supports a role for vitamin C in the formation of covalent adducts with electrophilic secondary metabolites. Mechanism-based effects of vitamin C and E supplementation on biomarkers and on clinical outcomes from randomized, placebo-controlled trials are emphasized in this review.
The liver is at the nexus of the regulation of lipoprotein uptake, synthesis, and secretion, and it is the site of xenobiotic detoxification by cytochrome P450 oxidation systems (phase I), ...conjugation systems (phase II), and transporters (phase III). These two major liver systems control vitamin E status. The mechanisms for the preference for α-tocopherol relative to the eight naturally occurring vitamin E forms largely depend upon the liver and include both a preferential secretion of α-tocopherol from the liver into the plasma for its transport in circulating lipoproteins for subsequent uptake by tissues, as well as the preferential hepatic metabolism of non-α-tocopherol forms. These mechanisms are the focus of this review.
Vitamin E, discovered in 1922, is essential for pregnant rats to carry their babies to term. However, 100 years later, the molecular mechanisms for the vitamin E requirement during embryogenesis ...remain unknown. Vitamin E's role during pregnancy has been difficult to study and thus, a vitamin E-deficient (E-) zebrafish embryo model was developed. Vitamin E deficiency in zebrafish embryos initiates lipid peroxidation, depletes a specific phospholipid (DHA-phosphatidyl choline), causes secondary deficiencies of choline, betaine and critical thiols (such as glutathione), and dysregulates energy metabolism. Vitamin E deficiency not only distorts the carefully programmed development of the nervous system, but it leads to defects in several developing organs. Both the α-tocopherol transfer protein and vitamin E are necessary for embryonic development, neurogenesis and cognition in this model and likely in human embryos. Elucidation of the control mechanisms for the cellular and metabolic pathways involved in the molecular dysregulation caused by vitamin E deficiency will lead to important insights into abnormal neurogenesis and embryonic malformations.
It is estimated that >90% of Americans do not consume sufficient dietary vitamin E, as α-tocopherol, to meet estimated average requirements. What are the adverse consequences of inadequate dietary ...α-tocopherol intakes? This review discusses health aspects where inadequate vitamin E status is detrimental and additional vitamin E has reversed the symptoms. In general, plasma α-tocopherol concentrations <12 μmol/L are associated with increased infection, anemia, stunting of growth, and poor outcomes during pregnancy for both the infant and the mother. When low dietary amounts of α-tocopherol are consumed, tissue α-tocopherol needs exceed amounts available, leading to increased damage to target tissues. Seemingly, adequacy of human vitamin E status cannot be assessed from circulating α-tocopherol concentrations, but inadequacy can be determined from “low” values. Circulating α-tocopherol concentrations are very difficult to interpret because, as a person ages, plasma lipid concentrations also increase and these elevations in lipids increase the plasma carriers for α-tocopherol, leading to higher circulating α-tocopherol concentrations. However, abnormal lipoprotein metabolism does not necessarily increase α-tocopherol delivery to tissues. Additional biomarkers of inadequate vitamin E status are needed. Urinary excretion of the vitamin E metabolite α-carboxy-ethyl-hydroxychromanol may fulfill this biomarker role, but it has not been widely studied with regard to vitamin E status in humans or with regard to health benefits. This review evaluated the information available on the adverse consequences of inadequate α-tocopherol status and provides suggestions for avenues for research.
α-Tocopherol (α-T) is a vitamin, but the reasons for the α-T requirement are controversial. Given that α-T deficiency was first identified in embryos, we studied to the premier model of vertebrate ...embryo development, the zebrafish embryo. We developed an α-T-deficient diet for zebrafish and used fish consuming this diet to produce α-T deficient (E−) embryos. We showed that α-T deficiency causes increased lipid peroxidation, leading to metabolic dysregulation that impacts both biochemical and morphological changes at very early stages in development. These changes occur at an early developmental window, which takes place prior to an analogous time to when a human knows she is pregnant. We found that α-T limits the chain reaction of lipid peroxidation and protects metabolic pathways and integrated gene expression networks that control embryonic development. Importantly, not only is α-T critical during early development, but the neurodevelopmental process is highly dependent on α-T trafficking by the α-T transfer protein (TTPa). Data from both gene expression and evaluation of the metabolome in E− embryos suggest that the activity of the mechanistic Target of Rapamycin (mTOR) signaling pathway is dysregulated—mTOR is a master regulatory mechanism, which controls both metabolism and neurodevelopment. Our findings suggest that TTPa is needed not only for regulation of plasma α-T in adults but is a key regulator during embryogenesis.
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•α-Tocopherol (α-T) is a controversial vitamin.•α-T deficiency causes increased lipid peroxidation.•α-T deficiency impacts both biochemical and morphological changes.•α-T protects metabolic pathways and integrated gene expression networks.•α-T in adults but is a key regulator during embryogenesis.
α-Tocopherol (α-T) is a required dietary nutrient for humans and thus is a vitamin. This narrative review focuses on vitamin E structures, functions, biological determinants and its deficiency ...symptoms in humans. The mechanisms for the preferential α-T tissue enrichment in the human body include the α-T transfer protein (TTPA) and the preferential metabolism of non-α-T forms. Potential new α-T biomarkers, pharmacokinetic data, and whether there are better approaches to evaluate and set the α-T dietary requirement are discussed. Finally, the possible role of α-T supplements in delay of chronic diseases and the evaluation of vitamin E safety are considered.
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•α-Tocopherol (α-T) is a required dietary nutrient for humans.•α-T deficiency in humans manifests as a progressive, peripheral neuropathy.•α-T is trafficked by the α-T transfer protein (TTPA).•The preference for α-T is maintained by the hepatic TTPA and catabolism of non-α-T.•α-CEHC, a product of catabolism, may be the best biomarker for VitE status.
Lipid peroxidation is the process by which oxygen combines with lipids to generate lipid hydroperoxides via intermediate formation of peroxyl radicals. Vitamin E and coenzyme Q
react with peroxyl ...radicals to yield peroxides, and then these oxidized lipid species can be detoxified by glutathione and glutathione peroxidase 4 (GPX4) and other components of the cellular antioxidant defense network. Ferroptosis is a form of regulated nonapoptotic cell death involving overwhelming iron-dependent lipid peroxidation. Here, we review the functions and regulation of lipid peroxidation, ferroptosis, and the antioxidant network in diverse species, including humans, other mammals and vertebrates, plants, invertebrates, yeast, bacteria, and archaea. We also discuss the potential evolutionary roles of lipid peroxidation and ferroptosis.
Vitamin E, antioxidant and nothing more Traber, Maret G.; Atkinson, Jeffrey
Free radical biology & medicine,
07/2007, Letnik:
43, Številka:
1
Journal Article
Recenzirano
Odprti dostop
All of the naturally occurring vitamin E forms, as well as those of synthetic
all-rac-α-tocopherol, have relatively similar antioxidant properties, so why does the body prefer α-tocopherol as its ...unique form of vitamin E? We propose the hypothesis that all of the observations concerning the in vivo mechanism of action of α-tocopherol result from its role as a potent lipid-soluble antioxidant. The purpose of this review then is to describe the evidence for α-tocopherol’s in vivo function and to make the claim that α-tocopherol’s major vitamin function, if not only function, is that of a peroxyl radical scavenger. The importance of this function is to maintain the integrity of long-chain polyunsaturated fatty acids in the membranes of cells and thus maintain their bioactivity. That is to say that these bioactive lipids are important signaling molecules and that changes in their amounts, or in their loss due to oxidation, are the key cellular events that are responded to by cells. The various signaling pathways that have been described by others to be under α-tocopherol regulation appear rather to be dependent on the oxidative stress of the cell or tissue under question. Moreover, it seems unlikely that these pathways are specifically under the control of α-tocopherol given that various antioxidants other than α-tocopherol and various oxidative stressors can manipulate their responses. Thus, virtually all of the variation and scope of vitamin E’s biological activity can be seen and understood in the light of protection of polyunsaturated fatty acids and the membrane qualities (fluidity, phase separation, and lipid domains) that polyunsaturated fatty acids bring about.
Dietary and supplemental vitamin E is absorbed and delivered to the liver, but of the various antioxidants with vitamin E activity, only alpha-tocopherol is preferentially recognized by the ...alpha-tocopherol transfer protein (alpha-TTP) and is transferred to plasma, while the other vitamin E forms (e.g., gamma-tocopherol or tocotrienols) are removed from the circulation. Hepatic alpha-TTP is required to maintain plasma and tissue alpha-tocopherol concentrations. The liver is the master regulator of the body's vitamin E levels in that it not only controls alpha-tocopherol concentrations, but also appears to be the major site of vitamin E metabolism and excretion. Vitamin Es are metabolized similarly to xenobiotics; they are initially omega-oxidized by cytochrome P450s, undergo several rounds of beta-oxidation, and then are conjugated and excreted. As a result of these various mechanisms, liver alpha-tocopherol and other vitamin E concentrations are closely regulated; thus, any potential adverse vitamin E effects are limited.
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