HEPATIC FATTY ACID OXIDATION AND CARNITINE METABOLISM

项目III：肝脏脂肪酸氧化和肉碱代谢 这个项目的长期目标是确定选址(S) 出现肝脏脂肪酸氧化缺陷的患者 作为后天或遗传基础上的雷耶氏综合征， 定义此缺陷与临床的关系 精神障碍的表现。为了实现这些目标， 本项目将检查缺陷的代谢后果 在脂肪酸氧化上的异常模式的产生 血浆脂肪酸与肉碱中间体的变化。 目的1鉴定和定量尿酰肉碱酯。 脂肪酸氧化缺陷患者使用高密度脂蛋白 高效液相色谱。 目标2是描述酶缺陷对脂肪的影响。 酸氧化对肉碱含量、酰基肉碱生产的影响 培养的成纤维细胞对肉碱的摄取和外排 存在脂肪酸底物。 目标3是测量血浆中和长链单链和 Reye综合征和其他已知疾病患者的二元酸 以及疑似脂肪酸氧化缺陷。 目标4是确定循环异常的来源 与脂肪酸缺陷相关的脂肪酸代谢物 用不同的抑制剂处理动物模型的氧化作用 这条小路。 这些研究将提高我们区分缺陷的能力 脂肪酸氧化检测前的临床方法 特异性酶的体外培养及对其发病机制的了解 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.