FATTY ALCOHOL METABOLISM IN SJOGREN-LARSSON SYNDROME

干燥-拉尔森综合征中的脂肪醇代谢

基本信息

批准号：
3242761
负责人：
WILLIAM B. RIZZO
金额：
$ 17.77万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-02-01 至 1992-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3242761
关键词：
Sjogren's syndrome alcohols aldehydes autosomal recessive trait brain metabolism congenital ichthyosis enzyme mechanism enzyme substrate fatty acid analog fibroblasts gas chromatography gene complementation human tissue laboratory rat liver cells mental retardation palmitates

项目摘要

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.

干燥-拉尔森综合征 (SLS) 是一种遗传性疾病以先天性鱼鳞病、智力低下为特征痉挛。初步研究表明，培养皮肤 SLS 患者的成纤维细胞改变了脂肪醇代谢由于缺乏脂肪醇酶：NAD-氧化还原酶（粮农组织）。人们对正常脂肪醇代谢知之甚少目前尚无关于改变脂肪的临床效果的信息酒精代谢。此外，人类粮农组织尚未特点。该提案的长期目标是了解正常的脂肪醇代谢以及FAO缺乏症是如何发生的可能导致SLS的临床表型。我们建议研究培养皮肤中的脂肪醇代谢来自正常人和 SLS 受试者的成纤维细胞来了解精神错乱的人 SLS 中的脂肪醇代谢。气液利用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在正常人成纤维细胞中并与残留的FAO相比 SLS 细胞中的活性以确定FAO酶是否是动力学或结构发生改变。我们将寻找基因使用基因互补分析来分析 SLS 中的异质性体细胞细胞融合技术。了解脂肪醇具有不同FAO活性的组织中的新陈代谢，将在大鼠肝细胞和大脑中进行代谢研究使用放射化学和酶技术进行组织切片。这参与脂肪醇代谢的酶的亚细胞定位将使用差异和方法确定途径密度梯度离心。 SLS的发病机制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。这些研究将提供有关正常脂肪醇代谢的基本信息和 SLS 中脂肪醇代谢紊乱。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Diagnosis of inborn errors of phytanic acid oxidation using tritiated phytanic acid.

使用氚化植烷酸诊断植烷酸氧化先天性疾病。

DOI：
发表时间：
1992
期刊：
Progress in clinical and biological research
影响因子：
0
作者：
Zenger-Hain,J;Craft,DA;Rizzo,WB
通讯作者：
Rizzo,WB

Prenatal diagnosis of Sjögren-Larsson syndrome using enzymatic methods.

使用酶法对干燥综合征进行产前诊断。

DOI：
10.1002/pd.1970140711
发表时间：
1994
期刊：
Prenatal diagnosis
影响因子：
3
作者：
Rizzo,WB;Craft,DA;Kelson,TL;Bonnefont,JP;Saudubray,JM;Schulman,JD;Black,SH;Tabsh,K;Dirocco,M;Gardner,RJ
通讯作者：
Gardner,RJ

Carrier detection for Sjögren-Larsson syndrome.

干燥综合征的携带者检测。