Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00242
M. Traber
Vitamin E (α-tocopherol, VitE) deficiency has been recognized for about 100 years to cause neurologic developmental failures and fetal death. Thus, VitE is a critical player in the biochemical and physiological networks that prevent the dysregulation of neurogenesis. The major concepts that are described herein include: (1) the antioxidant function of VitE along with glutathione to protect against peroxidative damage, (2) the recognition that highly peroxidizable lipids are necessary for nervous system development and (3) the interrelationships between phosphatidyl choline regulation, the choline/methylation cycle and the folate cycle. The discoveries from VitE deficient (E−) zebrafish show that oxidative and metabolic damage, along with behavioral and morphological abnormalities, are caused by inadequate VitE status. Prior to the onset of morphological abnormalities, E− embryos experience dysregulation of choline status, methylation patterns and energy generation with glucose depletion. Given the importance of healthy fetuses, the lack of understanding of VitE's role in regulation of embryogenesis represents a critical lack of knowledge about this key nutrient. Remarkably, most women have inadequate intakes of both VitE and choline, suggesting that inadequacy of one might potentiate the inadequacy of the other. Importantly, VitE inadequacy drives secondary deficiencies that cause developmental defects, especially neural tube defects. Specifically, the relationship of VitE, oxidative damage and metabolic control systems involved in neurogenesis are described.
{"title":"CHAPTER 17. Vitamin E Deficiency and Inadequacy; Insights Using Zebrafish, Lipidomics and Metabolomics","authors":"M. Traber","doi":"10.1039/9781788016216-00242","DOIUrl":"https://doi.org/10.1039/9781788016216-00242","url":null,"abstract":"Vitamin E (α-tocopherol, VitE) deficiency has been recognized for about 100 years to cause neurologic developmental failures and fetal death. Thus, VitE is a critical player in the biochemical and physiological networks that prevent the dysregulation of neurogenesis. The major concepts that are described herein include: (1) the antioxidant function of VitE along with glutathione to protect against peroxidative damage, (2) the recognition that highly peroxidizable lipids are necessary for nervous system development and (3) the interrelationships between phosphatidyl choline regulation, the choline/methylation cycle and the folate cycle. The discoveries from VitE deficient (E−) zebrafish show that oxidative and metabolic damage, along with behavioral and morphological abnormalities, are caused by inadequate VitE status. Prior to the onset of morphological abnormalities, E− embryos experience dysregulation of choline status, methylation patterns and energy generation with glucose depletion. Given the importance of healthy fetuses, the lack of understanding of VitE's role in regulation of embryogenesis represents a critical lack of knowledge about this key nutrient. Remarkably, most women have inadequate intakes of both VitE and choline, suggesting that inadequacy of one might potentiate the inadequacy of the other. Importantly, VitE inadequacy drives secondary deficiencies that cause developmental defects, especially neural tube defects. Specifically, the relationship of VitE, oxidative damage and metabolic control systems involved in neurogenesis are described.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90114604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00118
Shanshan Zhong, H. Yin
Lipids are amphiphilic organic molecules that are insoluble in aqueous environments and are important for maintaining membrane structures, providing energy through fatty acid β-oxidation and generating bioactive lipid mediators for signalling purposes. In particular, polyunsaturated fatty acid-containing lipids are not only important for maintaining the fluidity of the membrane but also for generating bioactive lipids through enzymatic processes or free radical mediated oxidation, termed lipid peroxidation (LPO). The free radical chain reactions can be intercepted by a good hydrogen atom donor, such as vitamin E (α-tocopherol). This chapter provides an overview of the chemical mechanisms of free radical lipid peroxidation and its biological relevance, focusing on the effects of vitamin E.
{"title":"CHAPTER 9. Lipid Peroxidation: Role of Vitamin E","authors":"Shanshan Zhong, H. Yin","doi":"10.1039/9781788016216-00118","DOIUrl":"https://doi.org/10.1039/9781788016216-00118","url":null,"abstract":"Lipids are amphiphilic organic molecules that are insoluble in aqueous environments and are important for maintaining membrane structures, providing energy through fatty acid β-oxidation and generating bioactive lipid mediators for signalling purposes. In particular, polyunsaturated fatty acid-containing lipids are not only important for maintaining the fluidity of the membrane but also for generating bioactive lipids through enzymatic processes or free radical mediated oxidation, termed lipid peroxidation (LPO). The free radical chain reactions can be intercepted by a good hydrogen atom donor, such as vitamin E (α-tocopherol). This chapter provides an overview of the chemical mechanisms of free radical lipid peroxidation and its biological relevance, focusing on the effects of vitamin E.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75630404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00257
S. Ikeda
The possibility that excessive vitamin E intake causes vitamin K deficiency bleeding has been recognized for a long time, but the cause is still unknown. We aimed to clarify the influence of vitamin E intake on vitamin K concentration and its physiological activity using rats. Intake of an α-tocopherol-containing diet lowered phylloquinone (PK) concentrations in various tissues except for the liver. α-Tocopherol suppressed the elevation of an extrahepatic PK concentration after oral administration of PK. However, the tissue concentration of menaquinone-4 (MK-4), another vitamin K isoform converted from PK in the body, did not decrease after α-tocopherol intake. Unlike α-tocopherol, intake of a γ-tocopherol-containing diet did not lower PK or MK-4 concentration in tissues, but excess intake of γ-tocopherol significantly decreased PK concentration in some extrahepatic tissues. Excess intake of α-tocopherol did not affect blood clotting activity, uncarboxylated osteocalcin concentration in the serum, bone density, or expression of the gene related to bone metabolism. These results revealed that α-tocopherol intake lowered extrahepatic PK concentration, but this decrease in PK concentration had little effect on vitamin K physiological activity in rats.
{"title":"CHAPTER 18. Interference Effect of Vitamin E on Vitamin K Metabolism","authors":"S. Ikeda","doi":"10.1039/9781788016216-00257","DOIUrl":"https://doi.org/10.1039/9781788016216-00257","url":null,"abstract":"The possibility that excessive vitamin E intake causes vitamin K deficiency bleeding has been recognized for a long time, but the cause is still unknown. We aimed to clarify the influence of vitamin E intake on vitamin K concentration and its physiological activity using rats. Intake of an α-tocopherol-containing diet lowered phylloquinone (PK) concentrations in various tissues except for the liver. α-Tocopherol suppressed the elevation of an extrahepatic PK concentration after oral administration of PK. However, the tissue concentration of menaquinone-4 (MK-4), another vitamin K isoform converted from PK in the body, did not decrease after α-tocopherol intake. Unlike α-tocopherol, intake of a γ-tocopherol-containing diet did not lower PK or MK-4 concentration in tissues, but excess intake of γ-tocopherol significantly decreased PK concentration in some extrahepatic tissues. Excess intake of α-tocopherol did not affect blood clotting activity, uncarboxylated osteocalcin concentration in the serum, bone density, or expression of the gene related to bone metabolism. These results revealed that α-tocopherol intake lowered extrahepatic PK concentration, but this decrease in PK concentration had little effect on vitamin K physiological activity in rats.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91258574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00012
J. Fu, Geetha Maniam, F. Wong, Doryn Meam-Yee Tan, P. Meganathan, L. Chuah
Since its discovery in the 1900s, vitamin E remains an essential micronutrient, playing a pivotal role as an antioxidant and neuroprotection agent. It is a family of compounds categorized into two groups based on chemical structure, i.e. tocopherols and tocotrienols. Although tocopherols are widely recognized due to their abundance in vegetable oils, little was known about tocotrienols. In fact, tocotrienols were found in high amounts in vegetable oils commonly used in Asian countries, including palm oil and rice bran oil. A recent shift in research focus revealed novel nutritional benefits of tocotrienols, beyond tocopherols. These nutritional benefits were extensively studied on a laboratory scale using in vitro and in vivo models. Moving into human studies, numerous clinical trials were conducted using commercial products of tocotrienols, marketed as tocopherol/tocotrienol mixtures. In addition to nutritional benefits, interest in the areas of their bioavailability, safety profile, and analytical methods have attracted global attention. In this chapter, we aim to address the research findings of tocotrienols over the past two decades, as well as the way forward. This review serves as a time-travel capsule, taking us on the journey of tocotrienol development from the bench to the bedside.
{"title":"CHAPTER 2. Tocotrienols: From Bench to Bedside","authors":"J. Fu, Geetha Maniam, F. Wong, Doryn Meam-Yee Tan, P. Meganathan, L. Chuah","doi":"10.1039/9781788016216-00012","DOIUrl":"https://doi.org/10.1039/9781788016216-00012","url":null,"abstract":"Since its discovery in the 1900s, vitamin E remains an essential micronutrient, playing a pivotal role as an antioxidant and neuroprotection agent. It is a family of compounds categorized into two groups based on chemical structure, i.e. tocopherols and tocotrienols. Although tocopherols are widely recognized due to their abundance in vegetable oils, little was known about tocotrienols. In fact, tocotrienols were found in high amounts in vegetable oils commonly used in Asian countries, including palm oil and rice bran oil. A recent shift in research focus revealed novel nutritional benefits of tocotrienols, beyond tocopherols. These nutritional benefits were extensively studied on a laboratory scale using in vitro and in vivo models. Moving into human studies, numerous clinical trials were conducted using commercial products of tocotrienols, marketed as tocopherol/tocotrienol mixtures. In addition to nutritional benefits, interest in the areas of their bioavailability, safety profile, and analytical methods have attracted global attention. In this chapter, we aim to address the research findings of tocotrienols over the past two decades, as well as the way forward. This review serves as a time-travel capsule, taking us on the journey of tocotrienol development from the bench to the bedside.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83930792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00088
Y. Suzuki, L. Marcocci, K. R. Duncan, D. I. Suzuki, N. Shults
Vitamin E nicotinate is an ester of tocopherol (vitamin E) and niacin (vitamin B3). While this ester can be chemically synthesized, whether vitamin E nicotinate is formed from vitamin E and niacin in the biological system is unclear. Our previous metabolomics analysis demonstrated that the heart tissue level of vitamin E nicotinate is 30-fold lower in heart failure. Since the rat diet used in these experiments contained vitamin E acetate and niacin separately, but not in the form of vitamin E nicotinate, these results revealed that vitamin E and niacin could be esterified to form vitamin E nicotinate in the biological system. Observations that the vitamin E nicotinate level gets altered in the disease state suggest clinical importance. While it was expected that oxidative stress occurring during heart failure decreases the levels of various antioxidants, only vitamin E nicotinate, but not other forms of vitamin E including α-tocopherol, was reduced. Hence, vitamin E nicotinate may function independently from simply serving as a source of active vitamin E. Consistent with this idea, we recently found that the intact vitamin E nicotinate structure could elicit cell signaling for the formation of anandamide. Exciting novel functions of vitamin E nicotinate are discussed.
{"title":"CHAPTER 7. Novel Functions of Vitamin E Nicotinate","authors":"Y. Suzuki, L. Marcocci, K. R. Duncan, D. I. Suzuki, N. Shults","doi":"10.1039/9781788016216-00088","DOIUrl":"https://doi.org/10.1039/9781788016216-00088","url":null,"abstract":"Vitamin E nicotinate is an ester of tocopherol (vitamin E) and niacin (vitamin B3). While this ester can be chemically synthesized, whether vitamin E nicotinate is formed from vitamin E and niacin in the biological system is unclear. Our previous metabolomics analysis demonstrated that the heart tissue level of vitamin E nicotinate is 30-fold lower in heart failure. Since the rat diet used in these experiments contained vitamin E acetate and niacin separately, but not in the form of vitamin E nicotinate, these results revealed that vitamin E and niacin could be esterified to form vitamin E nicotinate in the biological system. Observations that the vitamin E nicotinate level gets altered in the disease state suggest clinical importance. While it was expected that oxidative stress occurring during heart failure decreases the levels of various antioxidants, only vitamin E nicotinate, but not other forms of vitamin E including α-tocopherol, was reduced. Hence, vitamin E nicotinate may function independently from simply serving as a source of active vitamin E. Consistent with this idea, we recently found that the intact vitamin E nicotinate structure could elicit cell signaling for the formation of anandamide. Exciting novel functions of vitamin E nicotinate are discussed.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84657204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00208
P. Torquato, D. Giusepponi, R. Galarini, D. Bartolini, M. Piroddi, F. Galli
Enzymatic and non-enzymatic (free-radical-derived) metabolites of vitamin E are objects of increasing interest as both are indicators of the metabolism and biological functions of this fat-soluble vitamin. These include bioactive long-chain metabolites of alpha-tocopherol formed by the activity of cytochrome P450, which have recently been measured for the first time in human plasma using a new unbiased LC-MS/MS procedure. This chapter summarises the available knowledge on analysis strategies and techniques currently in use to measure the different types of metabolites of this vitamin so far identified and studied in biological samples.
{"title":"CHAPTER 15. Analysis of Vitamin E Metabolites","authors":"P. Torquato, D. Giusepponi, R. Galarini, D. Bartolini, M. Piroddi, F. Galli","doi":"10.1039/9781788016216-00208","DOIUrl":"https://doi.org/10.1039/9781788016216-00208","url":null,"abstract":"Enzymatic and non-enzymatic (free-radical-derived) metabolites of vitamin E are objects of increasing interest as both are indicators of the metabolism and biological functions of this fat-soluble vitamin. These include bioactive long-chain metabolites of alpha-tocopherol formed by the activity of cytochrome P450, which have recently been measured for the first time in human plasma using a new unbiased LC-MS/MS procedure. This chapter summarises the available knowledge on analysis strategies and techniques currently in use to measure the different types of metabolites of this vitamin so far identified and studied in biological samples.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89263610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00134
E. Niki
Aerobic organisms are always under threat from oxidative stress and have gained an efficient defense system against detrimental oxidative stress in the course of a long evolution. The antioxidant network is composed of multiple defense lines, in which versatile antioxidants with different functions play their respective roles. Vitamin E is one of the important members of the defense network and acts primarily as a lipophilic radical scavenging antioxidant to inhibit lipid peroxidation. Furthermore, non-antioxidant functions of vitamin E have been reported. The dynamics of the antioxidant action of vitamin E in heterogeneous media as well as in solution are described later. It must be noted that there remain many issues that should be demonstrated in order to fully understand the roles and effects of vitamin E in the maintenance of health and prevention of diseases.
{"title":"CHAPTER 10. Antioxidant Defense Network and Vitamin E","authors":"E. Niki","doi":"10.1039/9781788016216-00134","DOIUrl":"https://doi.org/10.1039/9781788016216-00134","url":null,"abstract":"Aerobic organisms are always under threat from oxidative stress and have gained an efficient defense system against detrimental oxidative stress in the course of a long evolution. The antioxidant network is composed of multiple defense lines, in which versatile antioxidants with different functions play their respective roles. Vitamin E is one of the important members of the defense network and acts primarily as a lipophilic radical scavenging antioxidant to inhibit lipid peroxidation. Furthermore, non-antioxidant functions of vitamin E have been reported. The dynamics of the antioxidant action of vitamin E in heterogeneous media as well as in solution are described later. It must be noted that there remain many issues that should be demonstrated in order to fully understand the roles and effects of vitamin E in the maintenance of health and prevention of diseases.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86288897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-04DOI: 10.1039/9781788016216-00151
L. Valgimigli, Riccardo Amorati
The search for novel antioxidants inspired by the structure of vitamin E was made possible by rationalization of the physical–chemical properties at the basis of vitamin E bioactivity and has contributed significantly to such rationalization. Hundreds of novel compounds have been synthesized and tested, a representative selection of which (51 molecules) is illustrated and discussed in this chapter, highlighting the structure–activity relationships behind their antioxidant activity. Among them, BO-653, thiatocopherol and related compounds, selenotocopherol and related compounds, tellurophenols, N-tocopherol and related compounds, and Mito-Vitamin E are given special attention. The discussion focuses on the absolute rate constant for trapping peroxyl radicals in solution. When available, the performance in biomimetic models, like the protection of low density lipoproteins, along with the results of in vivo testing for pharmaceutical applications is also addressed. Some of the synthetic analogues largely outperformed the most active natural α-tocopherol, both in model systems and in vivo. However, none of these compounds has yet reached medical practice or is currently approved as a pharmaceutical, which calls for further research.
{"title":"CHAPTER 11. Vitamin E Inspired Synthetic Antioxidants","authors":"L. Valgimigli, Riccardo Amorati","doi":"10.1039/9781788016216-00151","DOIUrl":"https://doi.org/10.1039/9781788016216-00151","url":null,"abstract":"The search for novel antioxidants inspired by the structure of vitamin E was made possible by rationalization of the physical–chemical properties at the basis of vitamin E bioactivity and has contributed significantly to such rationalization. Hundreds of novel compounds have been synthesized and tested, a representative selection of which (51 molecules) is illustrated and discussed in this chapter, highlighting the structure–activity relationships behind their antioxidant activity. Among them, BO-653, thiatocopherol and related compounds, selenotocopherol and related compounds, tellurophenols, N-tocopherol and related compounds, and Mito-Vitamin E are given special attention. The discussion focuses on the absolute rate constant for trapping peroxyl radicals in solution. When available, the performance in biomimetic models, like the protection of low density lipoproteins, along with the results of in vivo testing for pharmaceutical applications is also addressed. Some of the synthetic analogues largely outperformed the most active natural α-tocopherol, both in model systems and in vivo. However, none of these compounds has yet reached medical practice or is currently approved as a pharmaceutical, which calls for further research.","PeriodicalId":23674,"journal":{"name":"Vitamin E","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74056537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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