中文摘要
硬脂酰辅酶A去饱和酶(SCD),也称之为Δ9去饱和酶,是一个具四个跨膜域的调节脂肪合成和能量平衡的关键酶。SCD的表达和活性与脂肪积累、胰岛素抵抗等代谢性疾病高度相关。SCD的结构和功能、及其调控脂滴大小和脂肪储存的作用机理还有很多科学问题未知。基于我们前期一系列的研究工作基础,本项目拟开展以下研究:1)SCD活性与细胞色素b5还原酶和细胞色素b5的关系;2)锌(zinc)和铁(iron)与SCD活性和功能;3)SCD SNP位点或者氨基酸与其活性和功能;4)SCD影响脂滴大小的机理;5)影响SCD功能的新基因发掘及其作用机理研究。本项目的实施不仅扩大我们对SCD结构、功能、调控机制、及其在代谢性疾病中的作用机理的深入了解,也为SCD作为代谢性疾病的治疗靶标提供新的思路和策略。
英文摘要
Stearoly-CoA desaturase (SCD), also called delta-9 desaturase, is an ER membrane protein that plays key role in lipid biosynthesis and energy homeostasis. The expression and activity of SCD are highly associated with fat accumulation, insulin resistance, and other metabolic diseases. However, the structure and function of SCD and its regulation in lipid metabolism still remain elusive. In the last several years, we have been working on the regulation of SCD in lipid metabolism. Here, we continuously propose a series of new approaches to address the biological role of SCD in lipid metabolism. We will investigate the relationship of cytochrome b5 reductase, cytochrome b5 and SCD, determination of SCD activity by zinc or iron, characterization of SCD SNPs with its bioactivity and substrate preference, as well as the underlying mechanisms of lipid droplet regulation by SCD, and eventually the role of new SCD regulator. In conclusion, this work will further provide not only completely novel insights into the structure and activity of SCD, as well as its roles in the pathogenesis of metabolic diseases, but also new potential approaches or treatments for metabolic diseases by targeting SCD.
