Biophysical aspects of vitamin E

维生素 E 的生物物理方面

• 批准号: RGPIN-2015-06410
• 负责人: Harroun, Thad
• 金额: $ 2.55万
• 依托单位: Brock University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=653117
• 关键词: Biophysical; aspects; vitamin

Why is Vitamin E an essential vitamin?  Vitamin E is a strong antioxidant preservative in our food and personal care products. Vitamin E deficiencies are rare, however, healthy concentrations in our bodies are so low that some researchers are looking for reasons for consuming vitamin E other than oxidation protection. Worse still, there are no known health benefits for supplementing with vitamin E, and not for lack of trying. ***Thus the purpose for vitamin E is still hotly debated, over 90 years since its discovery. We are filling in several knowledge gaps of how tocopherol molecules (ie. vitamin E) interacts with the cell membrane. Our research goal is to convince physiologists that the demise of the antioxidant theory of tocopherol is premature.***We view tocopherol as a counterpoint to cholesterol in how lipid soluble molecules work among the lipids of the cell membrane. In brief; the molecular structure of tocopherol is just right to locate itself among the right lipids at the right place for oxidation protection. We have already seen that tocopherol location is not universal and suggested a means of free radical termination. This research proposal is designed to answer key questions: ***Does tocopherol target oxidation-sensitive lipids? Tocopherol should associate with the lipids that require oxidation protection. We will measure the association constants of the vitamin with lipids of varying degrees of unsaturation. Neutron and X-ray diffraction is our primary tool for structural determination, used to measure nanoscopic domains formed with tocopherol, as well as any asymmetric distribution in membranes. ***Does the disorder of unsaturated lipids help tocopherol? We can use monolayers to control the lipid chain order through surface pressure, and monitor how tocopherol slows oxidation damage. In an oxygen-free environment we control the rate of radical generation, and note the rate of lipid degradation. This deceptively simple experiment decouples the effects of stopping reactive oxygen species and termination of alkyl peroxyl radicals. ***Just what is the rate of tocopherol diffusion? Literature values of tocopherol's diffusion vary by orders of magnitude, due to poor controls and wrong test lipids. Using NMR, we will measure the diffusion rate of tocopherol to reveal any lipid preference. ****What is the effect of lipids on tocopherol's structure? Tocopherol has a chiral centre which can report on its molecular structure, and we have found a solvent polarity dependence. With synchrotron bright UV light, we will look for the effect of different lipids on its atomic structure. ***Are there lessons from tocopherol analogues? I am currently engaged in a commercial project exploring tocopherol-like molecules for cancer detection, but how they work is a general interest research topic. These new molecules differ from natural tocopherol in subtle ways and the above experiments will help us understand tocopherol better. ********

为什么维生素E是一种必需的维生素？ 维生素E是我们的食品和个人护理产品中的强抗氧化剂防腐剂。维生素E缺乏症是罕见的，然而，我们体内的健康浓度是如此之低，以至于一些研究人员正在寻找消耗维生素E而不是氧化保护的原因。更糟糕的是，补充维生素E没有已知的健康益处，而不是缺乏尝试。我们正在填补几个知识空白，如何生育酚分子（即。维生素E）与细胞膜相互作用。我们的研究目标是说服生理学家，生育酚的抗氧化理论的消亡还为时过早。我们认为生育酚是胆固醇的一种对应物，它与脂溶性分子在细胞膜的脂质中起作用。简而言之;生育酚的分子结构正好将其自身定位在合适的脂质中合适的位置以进行氧化保护。2我们已经看到生育酚的位置不是普遍的，并提出了一种自由基终止的方法。这项研究提案旨在回答关键问题：* 生育酚是否靶向氧化敏感性脂质？ 生育酚应该与需要氧化保护的脂质结合。我们将测量维生素与不同不饱和度脂质的缔合常数。中子和X射线衍射是我们用于结构测定的主要工具，用于测量生育酚形成的纳米级结构域以及膜中的任何不对称分布。* 不饱和脂质的紊乱是否有助于生育酚？我们可以使用单分子膜通过表面压力来控制脂质链的顺序，并监测生育酚如何减缓氧化损伤。在无氧环境中，我们控制自由基产生的速率，并注意脂质降解的速率。这个看似简单的实验证明了阻止活性氧和终止烷基过氧自由基的效果。生育酚扩散的速率是多少？生育酚扩散的文献值相差几个数量级，原因是控制不佳和试验脂质错误。使用核磁共振，我们将测量生育酚的扩散速率，以揭示任何脂质偏好。**** 脂质对生育酚的结构有什么影响？生育酚有一个手性中心，可以报告其分子结构，我们已经发现了溶剂极性依赖性。利用同步辐射明亮的紫外光，我们将寻找不同脂质对其原子结构的影响。* 是否有生育酚类似物的经验教训？ 我目前正在从事一个商业项目，探索用于癌症检测的生育酚样分子，但它们如何工作是一个普遍感兴趣的研究课题。这些新分子与天然生育酚有细微的不同，上述实验将有助于我们更好地了解生育酚。********