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INTESTINAL ASSIMILATION OF HYDROPHOBIC MOLECULES

疏水分子的肠道同化

基本信息

批准号：
3151733
负责人：
JOHN S PATTON
金额：
$ 8.1万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-07-01 至 1986-06-30
项目状态：
已结题

项目摘要

Humans injest a wide variety of hydrophobic or fat soluble molecules. While many of these substances are necessary micronutrients or drugs, many others are toxic and carcinogenic. Common examples include fossil fuel hydrocarbons, plasticizers, vitamin A, D, E, and K, many drugs and food additives, and numerous pollutants and biological control agents (e.g. PCBs, pesticides and herbicides). There has never been a satisfactory explanation of how such hydrophobic chemicals (aqueous solubilities of 10 to the -8 to 10 to the -14M) could be dispersed during digestion, and because of this it has generally been assumed that they are poorly absorbed. We have discovered that if a hydrophobic solute (such as the carcinogen benzo(a)pyrene) is dissolved in dietary fat droplets it will be quantitatively codispersed, coabsorbed, cotransported and coincorporated with the lipid into intracellular fat droplets in the enterocyte. These droplets of unrefined fat are then enzymatically "processed" and selectively purified before entering the circulation. The concept of indiscriminate lipid absorption followed by intracellular processing provides a completely new view of lipid assimilation that has profound significance for human health and disease; it explains how a large family of biologically important molecules can enter the body in high concentrations, it offers a mechanism to explain food chain magnification of xenobiotics, it reveals how otherwise insoluble carcinogens can be absorbed in high concentrations (edible oils are often seriously contaminated with carcinogens and high fat diets correlate with increased incidence of many human cancers), and it reveals a simple method of hydrophobic drug delivery. The aim of the proposed research is to determine the qualitative and quantitative carrying capacity of dietary fat for hydrophobic molecules during fat assimilation and to determine how fat can carry solutes through the microvillus membrane and cytosol. In vivo tracer and microscopy experiments and in vitro experiments with isolated microvillus membrane vesicles, intracellular fat droplets, and soluble cytosolic proteins will be conducted to help dissect the steps in the process of intestinal fat assimilation.

人类注射了各种各样的疏水性或脂溶性分子。虽然这些物质中有许多是必需的微量营养素或药物，其他则有毒和致癌。常见的例子包括化石燃料碳氢化合物，增塑剂，维生素A，D，E和K，许多药物和食品添加剂以及许多污染物和生物控制剂（例如，多氯联苯、杀虫剂和除草剂）。从来没有一个满意的说明这种疏水化学品（水溶解度为10 至-8至10至-14 M）可以在消化过程中分散，因此，人们普遍认为，全神贯注我们已经发现，如果疏水性溶质（如致癌物质苯并（a）芘）溶解在膳食脂肪滴中，定量共分散、共吸收、共转运和共掺入与脂质一起进入肠上皮细胞的细胞内脂肪滴。这些未精制的脂肪液滴然后被酶促“加工”，在进入循环之前被选择性地净化。的概念不分青红皂白的脂质吸收，然后是细胞内加工提供了一个全新的观点，脂质同化，对人类健康和疾病的重要性;它解释了一个大家庭如何生物学上重要的分子可以进入人体，浓度，它提供了一种机制来解释食物链放大它揭示了不溶性致癌物质如何高浓度吸收（食用油通常严重致癌物质污染和高脂肪饮食与增加许多人类癌症的发病率），它揭示了一种简单的方法，疏水性药物递送。拟议研究的目的是确定膳食脂肪的定性和定量承载能力在脂肪同化过程中疏水分子的作用，并确定脂肪能携带溶质穿过微绒毛膜和胞质溶胶。体内示踪剂和显微镜实验以及离体实验微绒毛膜囊泡、细胞内脂肪滴和可溶性胞质蛋白质将进行，以帮助解剖的步骤，肠道脂肪同化的过程。