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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614134
• 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是必不可少的维生素？维生素E在我们的食物和个人护理产品中是一种强大的抗氧化剂防腐剂。维生素E缺乏症很少见，然而，我们体内的健康浓度如此之低，以至于一些研究人员正在寻找服用维生素E的理由，而不是抗氧化。更糟糕的是，补充维生素E并没有已知的健康益处，而且不是因为缺乏尝试。 因此，在发现维生素E 90多年后，人们仍然在激烈争论维生素E的用途。我们正在填补关于生育酚分子(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，生育酚抗氧化理论的消亡还为时过早。 我们认为生育酚在脂溶分子如何在细胞膜的脂类之间发挥作用方面与胆固醇形成了对立面。总而言之，生育酚的分子结构恰到好处地将自己定位在合适的脂质中，在合适的地方进行氧化保护。我们已经看到生育酚的定位并不普遍，并建议了一种终止自由基的方法。这项研究提案旨在回答关键问题： 生育酚针对氧化敏感脂类吗？生育酚应该与需要氧化保护的脂质结合在一起。我们将测量维生素与不同程度不饱和脂质的结合常数。中子和X射线衍射是我们确定结构的主要工具，用于测量由生育酚形成的纳米结构域，以及膜中的任何不对称分布。 不饱和脂肪的紊乱对生育酚有帮助吗？我们可以使用单层膜通过表面压力来控制脂链的顺序，并监测生育酚如何减缓氧化损伤。在无氧环境中，我们控制自由基的生成速度，并注意脂肪降解的速度。这个看似简单的实验分离了阻止活性氧物种和终止烷基过氧基的效果。 生育酚的扩散速度到底有多快？生育酚扩散的文献值因控制不佳和错误的测试脂类而变化数量级。使用核磁共振，我们将测量生育酚的扩散速度，以揭示任何脂质偏好。 脂类对生育酚的结构有什么影响？生育酚有一个可以报告其分子结构的手性中心，我们发现了溶剂的极性依赖关系。利用同步辐射的强紫外光，我们将观察不同的脂类对其原子结构的影响。 生育酚类似物有什么启示吗？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类似分子，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微妙的区别，上述实验将帮助我们更好地了解生育酚。