NUTRITION AND METABOLISM--ABETALIPOPROTEINEMIA

对脂蛋白（和 载脂蛋白）在正常受试者和患者 血脂异常可以通过评估个体获得， 脂蛋白代谢的特殊先天性缺陷。 这项建议 请求持续营养和代谢支持 表型无β脂蛋白血症患者的研究 （ABL）。 为了检查夜间增加的 甲羟戊酸的血浆浓度（其平行于 胆固醇生物合成增加） 反映了肝脏缺乏对乳糜微粒残留的摄取，我们 建议检查营养和激素对 患者血浆中甲羟戊酸的浓度 与对照受试者和ABL患者相比， 对ABL患者的研究将 检查载脂蛋白E的代谢周转率， HDL的载脂蛋白A1部分，确定是否 免疫学可检测的载脂蛋白B存在于 纯合子HBL患者的肠粘膜， 确定我们之前表现出的肾上腺功能受损 ABL对ACTH刺激的反应可以通过 输注LDL。 我们最近证明了血浆中 纯合子HBL患者妊娠期孕酮 以及维持妊娠的生物学能力。 我们提出 检查这个病人的胎盘是否增加 胆固醇生物合成和低密度脂蛋白受体活性， 以弥补母体低密度脂蛋白的缺乏， ABL患者血浆中存在的脂蛋白， 孕酮生物合成的胆固醇。 人乳 甘油三酸酯被认为是由脂肪酸 存在于富含甘油三酯的脂蛋白中， 母乳成分将进行，以确定如何 这是由于固有的乳糜微粒缺乏的影响， 预测的异常脂肪酸组成是否可以 通过血管内输注外源性药物进行修饰 甘油三酸酯乳剂（Intraperoid）。 维生素E的吸收和 ABL中的转运异常。我们计划检查维生素 E携带在ABL血浆中，无论他们的HDL颗粒 能够以类似的方式将维生素E输送到细胞 LDL在正常人中的作用方式 最后，已开始进行合作研究， ABL中的分子缺陷，即载脂蛋白B基因 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.