In vivo dynamic of beta-Carotene Metabolism in Humans

描述（由申请方提供）：富含三酰甘油的脂蛋白颗粒从肠（乳糜微粒）和肝（VLDL）来源的延迟清除正在成为动脉粥样硬化的主要风险因素，然而，尚不清楚高甘油三酯血症是否是分泌、水解和/或颗粒摄取的缺陷。因此，示踪研究，可以量化率的过程，如极低密度脂蛋白合成率或乳糜微粒清除率，已成为一个高度的科学优先事项。β-胡萝卜素（β-CAR）和维生素A是脂溶性营养素，其命运与脂蛋白载体有关。因此，对这些化合物的命运的研究揭示了脂蛋白系统的基本结构和动力学的信息，这反过来又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和类维生素A在脂质转运系统背景下的化学预防和动脉粥样硬化中的作用，消耗14 C标记的β-CAR和棕榈酸视黄酯，并测定脂蛋白亚类和排泄液（尿液和粪便）中标记物的浓度时程。加速器质谱法（AMS）可促进此类体内研究：AMS可从毫克大小的生化样品中定量14 C标记化合物的阿托摩尔（10-18摩尔）或阿托居里，从而能够在相关饮食水平下进行研究（7，8）。我们的长期目标是描述人体中β-CAR和维生素A代谢的动态行为，最终开发出一种对疾病发生和发展的遗传和环境决定因素敏感的人体生理预测模型。为了实现这一目标，我们的直接目标是阐明在真实示踪剂剂量后14 C标记的β-CAR和维生素A在人脂蛋白中的摄取和分布。重点将给予标记的β-CAR和维生素A及其代谢产物之间的肠和肝源性富三酰甘油（TRL）脂蛋白亚类在餐后阶段的差异分布，在这样做，这些化合物的吸收的化学和解剖途径的方面将被解释。

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.