DIETARY CAROTENOIDS--TRANSPORT IN HUMAN PLASMA

类胡萝卜素是四萜色素，其从头生物合成是 仅限于植物和微生物。因此，人类从以下物质中获取类胡萝卜素： 通过摄入水果和蔬菜的饮食。历史上，它是 认为某些类胡萝卜素在人类饮食中最重要的作用 是它们代谢转化为必需的微量营养素维生素 A （视黄醇），事实上，食用含类胡萝卜素的食物可以满足 许多人维生素 A 需求的重要组成部分。更多 最近，膳食类胡萝卜素的其他重要作用是 有人建议，它们与维生素 A 的转化无关。在 特别是，最近的研究表明类胡萝卜素可以抑制 由于其内在特性而导致致癌和脂蛋白氧化 作为脂溶性抗氧化剂。因此，类胡萝卜素可能有助于预防这两种癌症 和动脉粥样硬化性心脏病。尽管有这些潜在的重要 其在人类健康中的作用，目前关于其详细信息还很少 类胡萝卜素在人血浆中的转运。目前的目标 提案旨在定义类胡萝卜素在人体中的运输系统 血浆以及这些化合物在预防或延迟中的作用 脂蛋白氧化。在 AIM 1 下，我们将确定 人血浆脂蛋白中的单个类胡萝卜素。这将完成 通过分离脂蛋白、提取类胡萝卜素并通过以下方法对其进行定量 高效液相色谱法。我们将检验以下假设： 脂溶性类胡萝卜素将与血浆结合 脂蛋白。在 AIM 2 下，我们将探讨个人的作用 类胡萝卜素可保护血浆脂蛋白免于氧化。隔离 脂蛋白在体外会被氧化并消失的动力学 内源性类胡萝卜素的减少和氧化脂质的出现将 通过化学分析评估。脂蛋白的生物学后果 将使用功能测定来评估氧化。我们将测试 假设脂蛋白的氧化直到内源性才发生 类胡萝卜素被破坏。在 AIM 3 下，我们将富集脂蛋白 通过口服摄入类胡萝卜素来检测单个类胡萝卜素，看看这是否 导致脂蛋白对氧化损伤的抵抗力增强。我们 将检验增加类胡萝卜素消耗的假设 保护脂蛋白免受氧化。

Carotenoids are tetraterpene pigments whose de novo biosynthesis is restricted to plants and microorgamsms. Thus, humans obtain carotenoids in the diet by the ingestion of fruits and vegetables. Historically, it was thought that the most important role of some carotenoids in the human diet was their metabolic conversion to the essential micronutrient, vitamin A (retinol), and indeed, consumption of carotenoid-containing foods fulfills a significant part of the vitamin A requirement of many humans. More recently, other important roles for dietary carotenoids which are independent of their conversion to vitamin A have been suggested. In particular, recent studies suggest that carotenoids can inhibit both carcinogenesis and lipoprotein oxidation due to their intrinsic properties as fat soluble antioxidants. Thus carotenoids may help prevent both cancer and atherosclerotic heart disease. In spite of these potentially important roles in human health, little detailed information is available on the transport of carotenoids in human plasma. The objective of the present proposal is to define the transport systems for carotenoids in human plasma and the role of these compounds in preventing or retarding lipoprotein oxidation. Under AIM 1 we will determine the distribution of individual carotenoids among human plasma lipoproteins. This will be done by isolating lipoproteins, extracting carotenoids and quantitating them by high performance liquid chromatography. We will test the hypothesis that the lipid-soluble carotenoids will be associated with the plasma lipoproteins. Under AIM 2, we will explore the role of individual carotenoids in protecting plasma lipoproteins from oxidation. Isolated lipoproteins will be oxidized in vitro and the kinetics of disappearance of endogenous carotenoids and the appearance of oxidized lipids will be assessed by chemical analyses. The biological consequences of lipoprotein oxidation will be assessed using functional assays. We will test the hypothesis that oxidation of lipoproteins does not occur until endogenous carotenoids are destroyed. Under AIM 3 we will enrich the lipoproteins in individual carotenoids by oral ingestion of carotenoids and see if this leads to increased resistance of the lipoproteins to oxidative damage. We will test the hypothesis that increased consumption of carotenoids protects lipoproteins from oxidation.