NUTRITION AND METABOLISM--ABETALIPOPROTEINEMIA

对脂蛋白的作用有相当深入的了解(和 载脂蛋白)在正常人和糖尿病患者中的表达 通过评估符合以下条件的个体可获得血脂异常 脂蛋白代谢的特定先天缺陷。这项建议 请求对持续营养和代谢的支持 表型载脂蛋白血症患者的调查 (ABL)。以检查夜间活动是否增加 甲伐他酸的血浆浓度(与 胆固醇生物合成增加)在正常人中可见 反映肝脏对乳杆菌残留物缺乏摄取，我们 建议研究营养和荷尔蒙对 甲伐他酸在患者血浆中的浓度 ABL患者与对照受试者相比，以及一名患有 正常的甘油三酯血症。对ABL患者的研究将 检测载脂蛋白E和载脂蛋白E的代谢代谢 载脂蛋白A1部分高密度脂蛋白，决定是否 免疫检测到的载脂蛋白B存在于 1例HBL纯合子患者的肠粘膜 确定我们之前证实的肾上腺功能受损 ABL对ACTH刺激的反应可通过 输注低密度脂蛋白。我们最近展示了血浆浓度的降低 1例纯合子HBL患者孕期孕酮水平 以及维持妊娠的生物学能力。我们建议 检查该患者的胎盘是否增加 胆固醇生物合成和低密度脂蛋白受体活性的尝试 以弥补母体低密度脂蛋白的缺乏和 ABL患者血浆中存在的脂蛋白可供 胆固醇用于黄体酮的生物合成。人乳 甘油三酯被认为是从脂肪酸中衍生出来的 富含甘油三酯的脂蛋白及其脂类的研究 将对母乳进行成分分析，以确定如何 这是受固有的缺乏乳糜管和 预测的异常脂肪酸组成是否可以 通过血管内输注外源性 甘油三酯乳剂(Intralipid)。维生素E的吸收和 ABL的运输异常。我们计划检查维他命 E是在ABL血浆中携带的，无论它们的高密度脂蛋白颗粒 能以类似的方式将维生素E输送到细胞中 人们认为低密度脂蛋白在正常受试者中的作用方式。 最后，已经启动了合作研究，以审查 载脂蛋白B基因在ABL中的分子缺陷 已经被克隆了。

Considerable insight into the roles of lipoproteins ( and apoproteins) in normal subjects and patients with dyslipoproteinemias can be gained by evaluating individuals with specific inborn errors of lipoprotein metabolism. This proposal request support for continued nutritional and metabolic investigations in patients with phenotypic abetalipoproteinemia (ABL). To examine whether or not the nocturnal increase in plasma concentrations of mevalonic acid ( which parallel an increase in cholesterol biosynthesis) seen in normal subjects reflects a lack of hepatic uptake of chylomicron remnants, we propose to examine nutritional and hormonal influences on the concentrations of the mevalonic acid in the plasma of patients with ABL as compared to control subjects and a patient with normotriglyceridemic ABL. Studies in patients with ABL will examine the metabolic turnover of the apoprotein E and apoprotein A1 moieties of HDL, determine whether or not immunologically detectable apoprotein B is present in the intestinal mucosa of a patient with homozygous HBL and determine whether our previously demonstrated impaired adrenal response to ACTH stimulation in ABL can be corrected by an infusion of LDL. We have recently demonstrated reduced plasma progesterone during pregnancy in a patient with homozygous HBL and the biological capability to maintain pregnancy. We propose to examine whether the placenta of this patient increases cholesterol biosynthesis and LDL receptor activity in an attempt to compensate for the lack of maternal LDL and the ability of lipoproteins present in the plasma of patients with ABL to supply cholesterol for progesterone biosynthesis. Human milk triglycerides are believed to be derived from the fatty acids present in triglyceride-rich lipoproteins and studies on the lipid composition of breast milk will be conducted to determine how this is influenced by the inherent absence of chylomicrons and whether the predicted abnormal fatty acid composition can be modified by the intravascular infusion of an exogenous triglyceride emulsion (Intralipid). Vitamin E absorption and transport is abnormal in ABL. We plan to examine where vitamin E is carried in ABL plasma and whether or not their HDL particles can function to deliver vitamin E to cells in a manner analagous to the way LDL is believed to function in normal subjects. Finally, collaborative studies have been initiated to examine the molecular defect in ABL now that the gene for apolipoprotein B has been cloned.