FATTY ALCOHOL METABOLISM IN SJOGREN-LARSSON SYNDROME

干燥综合征（SLS）是一种遗传性疾病， 以先天性鱼鳞病、智力迟钝和 痉挛 初步研究表明， 来自SLS患者的成纤维细胞改变了脂肪醇代谢 由于缺乏酶，脂肪醇：NAD-氧化还原酶 （粮农组织）。 正常的脂肪醇代谢知之甚少， 目前还没有关于改变脂肪酸的临床效果的信息， 酒精代谢。 此外，人类粮农组织还没有 表征了 这项建议的长远目标是 了解正常的脂肪醇代谢和如何FAO缺乏 可能导致SLS的临床表型。 我们建议在培养的皮肤中研究脂肪醇代谢 正常和SLS受试者的成纤维细胞，以了解精神错乱的 脂肪醇代谢的SLS。 利用气液两相流技术 色谱法与放射化学示踪剂研究相结合， 我们将研究脂肪醇水平的调节， 正常和SLS成纤维细胞。 粮农组织活动的特点是 在正常人成纤维细胞中， 在SLS细胞中的活性，以确定FAO酶是否 在动力学上或结构上改变的。 我们将寻找基因 通过基因互补分析，使用 体细胞核融合技术。 了解脂肪醇 在FAO活性差异很大的组织中进行代谢， 将在大鼠肝细胞和脑中进行代谢研究 使用放射化学和酶技术的组织切片。 的 脂肪醇代谢酶的亚细胞定位 将使用微分和 密度梯度离心。 SLS的发病机制将是 在大鼠喂养研究中进行调查，以确定组织是否 脂肪醇积累导致生化和临床 改变SLS的特性。 这些研究将提供 关于正常脂肪醇代谢的基本信息， SLS中紊乱的脂肪醇代谢

Sjogren-Larsson syndrome (SLS) is an inherited disorder characterized by congential ichthyosis, mental retardation and spasticity. Preliminary studies show that cultured skin fibroblasts from SLS patients have altered fatty alcohol metabolism due to deficiency of the enzyme, fatty alcohol: NAD- oxidoreductase (FAO). Normal fatty alcohol metabolism is poorly understood and no information is known about the clinical effects of altered fatty alcohol metabolism. Furthermore, human FAO has not been characterized. A long-term objective of this proposal is to understand normal fatty alcohol metabolism and how FAO deficiency may lead to the clinical phenotype of SLS. We propose to investigate fatty alcohol metabolism in cultured skin fibroblasts from normal and SLS subjects to understand the deranged fatty alcohol metabolism in SLS. Using techniques of gas-liquid chromatography in combination with radiochemical tracer studies, we will investigate the regulation of fatty alcohol levels in normal and SLS fibroblasts. FAO acitivity will be characterized in normal human fibroblasts and compared to the residual FAO activity in SLS cells to determine whether the FAO enzyme is kinetically or structurally altered. We will search for genetic heterogeneity in SLS by gene complementation analysis using the techniques of somatic cll fusion. To uderstand fatty alcohol metabolism in tissues with quite different FAO activities, metabolic studies will be performed in rat hepatocytes and brain tissue slices using radiochemnical and enzymatic techniques. The subcellualr location of enzymes involved in fatty alcohol metabolic pathways will be determined using methods of differential and density-gradient centrifugation. The pathogenesis of SLS will be investigate in rat feeding studies to establish whether tissue fatty alcohol accumulation leads to biochemical and clinical changes characteristic of SLS. These studies will provide fundamental information about normal fatty alcohol metabolism and the deranged fatty alcohol metabolism in SLS.