Role of Acyl-CoA Synthetase-5 in Fatty Acid Partitioning

酰基辅酶A合成酶5在脂肪酸分配中的作用

• 批准号: 6551915
• 负责人: CYNTHIA G VAN HORN
• 金额: $ 4.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-08 至 2003-07-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6551915
• 关键词: acid thiol ligase; acyl coA; acyltransferase; antisense nucleic acid; bioenergetics; enzyme mechanism; fatty acid metabolism; glycerophosphates; isozymes; laboratory mouse; lipid biosynthesis; liver cells; postdoctoral investigator; tissue /cell culture

DESCRIPTION (provided by applicant): Nutrition-related diseases such as obesity and diabetes mellitus exhibit defective acyl-CoA partitioning which affects beta-oxidation and triacylglycerol stores. Acyl CoA synthetase (ACS) catalyzes the first step in fatty acid The purpose of this study is to identify the role of the ACS5 isoform in fatty acid partitioning between pathway energy production and glycerolipid synthesis. ACS5 and ACS5 antisense mRNA will be overexpressed in primary hepatocyte cultures via recombinant adenoviral technology. Incorporation of 14-C oleate into products of beta oxidation and lipid synthesis will be measured to determine the effects of excess or reduced enzyme levels on pathways. Additionally, ACS5 will be expressed in primary hepatocytes isolated from mice lacking function mitochondrial glycerol-3-phosphate acyltransferase (GPAT), which catalyzes the initial step in glycerolipid synthesis. These experiments will determine if excess or reduced enzyme levels of ACS5 alter rates of beta-oxidation and lipid synthesis in the presence and absence of GPAT, reduce the metabolic effects of hormonal stimuli, or increase lipid synthesis when beta-oxidation is inhibited. We hypothesize that ACS5 participates in fatty acid partitioning by providing acyl-CoAs primarily for energy production by beta-oxidation.

描述（由申请人提供）：营养相关疾病，例如肥胖症和糖尿病，表现出酰基辅酶A分配缺陷，影响β-氧化和三酰基甘油储存。酰基 CoA 合成酶 (ACS) 催化脂肪酸的第一步本研究的目的是确定 ACS5 同工型在脂肪酸在途径能量产生和甘油脂合成之间分配中的作用。 ACS5和ACS5反义mRNA将通过重组腺病毒技术在原代肝细胞培养物中过表达。将测量 14-C 油酸掺入 β 氧化和脂质合成产物中的情况，以确定过量或减少的酶水平对途径的影响。此外，ACS5 将在从缺乏功能线粒体甘油-3-磷酸酰基转移酶 (GPAT) 的小鼠分离的原代肝细胞中表达，该酶催化甘油脂合成的初始步骤。这些实验将确定 ACS5 酶水平过量或降低是否会改变 GPAT 存在和不存在时的 β 氧化和脂质合成速率，减少激素刺激的代谢作用，或在抑制 β 氧化时增加脂质合成。我们假设 ACS5 通过提供酰基辅酶 A 参与脂肪酸分配，主要用于通过 β 氧化产生能量。