In vivo dynamic of beta-Carotene Metabolism in Humans

描述（由申请人提供）：富含三酰甘油的脂蛋白颗粒从肠道（乳糜微粒）和肝脏（VLDL）来源的延迟清除正成为动脉粥样硬化的主要危险因素，然而，尚不清楚高甘油三酯血症是否是分泌、水解和/或颗粒摄取方面的缺陷。因此，可以量化速率过程的示踪剂研究，如VLDL合成速率或乳糜微粒清除率，已成为一个高度优先的科学研究方向。β -胡萝卜素（β -car）和维生素A是脂溶性营养素，它们的命运与其脂蛋白载体有关。因此，对这些化合物命运的研究揭示了脂蛋白系统的潜在结构和动力学信息，从而阐明了类胡萝卜素和类维生素a在健康和疾病中的作用。为了确定β - car和类视黄醇在脂质转运系统中的化学预防和动脉粥样硬化中的作用，消耗了14C标记的β - car和视黄醇棕榈酸酯，并测定了标记的浓度随时间变化的脂蛋白亚类和排泄液体（尿液和粪便）。加速器质谱法（AMS）为这种体内研究提供了便利：AMS可以量化毫克级生化样品中14c标记化合物的原子摩尔（10-18摩尔）或原子居里，从而可以在相关的饮食水平上进行研究（7,8）。我们的长期目标是描述人体内β - car和维生素A代谢的动态行为，最终开发一种对疾病发生和发展的遗传和环境决定因素敏感的人类生理预测模型。为了实现这一目标，我们的直接目标是阐明在真正的示踪剂剂量后，14C标记的β - car和维生素A在人脂蛋白中的摄取和分布。重点将放在餐后阶段标记β - car和维生素A及其代谢物在肠道和肝脏富三酰甘油（TRL）脂蛋白亚类中的差异分布；在此过程中，这些化合物的化学和解剖学吸收途径的各个方面将得到解释。

DESCRIPTION (provided by applicant): Delayed clearance of triacylglycerol-rich lipoprotein particles from intestinal (chylomicrons) and hepatic (VLDL) origins is emerging as a leading risk factor for atherosclerosis, however, it is unclear whether hypertriglyceridemia is a defect in secretion, hydrolysis, and/or particle uptake. As a result, tracer studies that can quantify rate processes, such as VLDL synthetic rates or chylomicron clearance rates, have emerged as a high scientific priority. Beta-carotene (beta-CAR) and vitamin A are lipid soluble nutrients whose fates are linked to their lipoprotein carriers. Accordingly, investigations on the fate of these compounds reveal information on the underlying structure and dynamics of the lipoprotein system, which in turn, clarifies the role of carotenoids and retinoids in health and disease. To establish the role of beta-CAR and retinoids in chemoprevention and atherosclerosis in the context of lipid transporting systems, 14C labeled beta-CAR and retinyl palmitate is consumed and the concentration time-course of the label is determined into lipoprotein subclasses and excretory fluids (urine and stool). Such in vivo investigations are facilitated by Accelerator Mass Spectrometry (AMS): AMS can quantify attomoles (10-18 moles) or attoCuries of 14C-labeled compounds from milligram-sized biochemical samples enabling studies at relevant dietary levels (7, 8). Our long-range goal is to describe the dynamic behavior of beta-CAR and vitamin A metabolism in humans, ultimately developing a predictive model of human physiological that is sensitive to the genetic and environmental determinants of disease initiation and progression. In pursuit of this goal, our immediate objectives are to elucidate the uptake and distribution of 14C labeled beta-CAR and vitamin A among human lipoproteins following a true tracer dose. Emphasis will be given to the differential distribution of labeled beta-CAR and vitamin A and their metabolites among the intestinal and hepatogeneous triacylglyceride-rich (TRL) lipoproteins subclasses in the postprandial phase; in doing so, aspects of the chemical and anatomical pathways of absorption for these compound will be explained.