METABOLISM OF UNSATURATED AND HYDROXY FATTY ACIDS

不饱和脂肪酸和羟基脂肪酸的代谢

• 批准号: 2216713
• 负责人: HORST H SCHULZ
• 金额: $ 17.29万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2216713
• 关键词: Escherichia coli; cis trans isomerization; eicosanoid metabolism; enzyme complex; enzyme deficiency; enzyme mechanism; fatty acid metabolism; fibroblasts; fluorimetry; gene expression; hormone regulation /control mechanism; human tissue; hydroxy fatty acid; inborn metabolism disorder; isomerase; laboratory rat; lymphoblast; mitochondria; molecular cloning; myristates; nucleic acid sequence; oxidation; oxidoreductase; peroxisome; somatotropin; thyroxine; tissue /cell culture; unsaturated fatty acids; western blottings

This project is designed to answer a number of questions and provide information important for developing a detailed understanding of the beta- oxidation of polyunsaturated fatty acids (PUFA) and hydroxy fatty acids. The focus of this study will be on 2,4-dienoyl-CoA reductase and 3- hydroxyacyl-CoA epimerase which are key enzymes in the reductase-dependent and epimerase-dependent pathways of PUFA beta-oxidation, respectively. Biochemical and genetic approaches will be used to study the beta-oxidation system of mammals and E. coli. An important aspect of this study is an assessment of the importance of 3-hydroxyacyl-CoA epimerase in the beta- oxidation of hydroxy fatty acids like D-5 hydroxymyristic acid in E. coli. Also, the mechanism o the E. coil 3-hydroxyacyl-CoA epimerase will be elucidated as will be in the location of delta3-cis-delta2 trans-enoyl-CoA isomerase on the multienzyme complex of fatty acid oxidation from E. coli. The identification of a human disorder due to a deficiency of 2,4-dienoyl- CoA reductase prompts further studies of this enzyme including (a) the development of a more sensitive assay to measure reductase from rat liver; (c) the cloning, sequencing and overexpression of the E. coli reductase gene; (d) a stereochemical study of the reduction catalyzed by mammalian 2,4-dienoyl-CoA reductase and (e) the hormonal regulation of this enzyme and its effect on PUFA beta-oxidation. Finally, the beta-oxidation of cis and trans unsaturated fatty acids in mitochondria will be studied with the aim of detecting and explaining differences in their degradation. Although, this project will provide a more complete view of the beta- oxidation of polyunsaturated fatty acids and some hydroxy fatty acids in normal an diseased organisms including humans.

该项目旨在回答一些问题并提供 对于详细了解 beta 非常重要的信息 多不饱和脂肪酸（PUFA）和羟基脂肪酸的氧化。 本研究的重点是 2,4-二烯酰辅酶 A 还原酶和 3- 羟酰辅酶A差向异构酶是还原酶依赖性的关键酶 分别是PUFA β-氧化的差向异构酶依赖性途径。 生化和遗传学方法将用于研究β-氧化 哺乳动物和大肠杆菌系统。 这项研究的一个重要方面是 评估 3-羟酰基-CoA 差向异构酶在 β- 中的重要性 大肠杆菌中羟基脂肪酸（如 D-5 羟基肉豆蔻酸）的氧化。 此外，大肠杆菌 3-羟酰基-CoA 差向异构酶的机制将是 已阐明将在 delta3-cis-delta2 trans-enoyl-CoA 的位置 大肠杆菌脂肪酸氧化多酶复合物上的异构酶。 鉴定由于 2,4-二烯酰基- 缺乏引起的人类疾病 CoA 还原酶促进了对该酶的进一步研究，包括 (a) 开发一种更灵敏的测定法来测量大鼠肝脏的还原酶； (c) 大肠杆菌还原酶的克隆、测序和过表达 基因; (d) 哺乳动物催化还原反应的立体化学研究 2,4-二烯酰辅酶A还原酶和 (e) 该酶的激素调节 及其对 PUFA β-氧化的影响。 最后，顺式的β-氧化 线粒体中的反式不饱和脂肪酸将与 目的是检测和解释其降解的差异。 尽管如此，这个项目将提供测试版的更完整的视图- 多不饱和脂肪酸和一些羟基脂肪酸的氧化 正常和患病的生物体，包括人类。