HEPATIC FATTY ACID OXIDATION AND CARNITINE METABOLISM

项目三：肝脂肪酸氧化与肉毒碱代谢 本项目的长期目标是确定 肝脂肪酸氧化缺陷的患者， 雷氏综合征的获得性或遗传性基础上， 定义该缺陷与临床 疾病的表现。 为了实现这些目标， 本项目将研究缺陷的代谢后果 在脂肪酸氧化对产生异常模式的 血浆脂肪酸和肉毒碱中间体的改变。 目的1是鉴定和定量尿酰基肉毒碱酯， 脂肪酸氧化缺陷患者使用高 高效液相色谱法 目的2是表征脂肪酶缺陷的影响， 酸氧化对肉毒碱含量的影响，酰基肉毒碱的产生， 生长在培养的成纤维细胞中的肉毒碱摄取和流出 存在脂肪酸底物。 目的3是测量血浆中链和长链单-和 二羧酸在Reye综合征患者和其他已知的 和脂肪酸氧化的疑似缺陷。 目的4是确定循环异常的起源， 与脂肪酸缺陷相关的脂肪酸代谢物 使用用各种氧化抑制剂处理的动物模型， 道路。 这些研究将提高我们区分缺陷的能力， 在测定前使用临床方法进行脂肪酸氧化 体外特异性酶，并了解 这些疾病。

Project III: Hepatic Fatty Acid Oxidation and Carnitine Metabolism The long-term goals of this project are to determine the site(s) of defect in hepatic fatty acid oxidation in patients who present as Reye's syndrome on either an acquired or a genetic basis and to define the relationship of this defect to the clinical manifestations of the disorder. To accomplish these goals, the present project will examine the metabolic consequences of defects in fatty acid oxidation on the generation of abnormal patterns of plasma fatty acids and alterations in carnitine intermediates. Aim 1 is to identify and quantify urinary acyl-carnitine esters in patients with defects in fatty acid oxidation using high performance liquid chromatography. Aim 2 is to characterize the effects of enzymatic defects in fatty acid oxidation on carnitine content, acyl-carnitine production, and carnitine uptake and efflux in cultured fibroblasts grown in the presence fatty acid substrates. Aim 3 is to measure plasma medium- and long-chain mono- and dicarboxylic acids in patients with Reye's syndrome and other known and suspected defects in fatty acid oxidation. Aim 4 is to determine the origin of abnormalities in circullating fatty acid metabolites associated with defects in fatty acid oxidation using animal models treated with various inhibitors of the pathway. These studies will improve our ability to distinguish defects in fatty acid oxidation using clinical methods prior to assay of specific enzymes in-vitro and to understand the pathogenesis of these diseases.