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机构地区:[1]上海交通大学医学遗传研究所,上海市儿童医院,上海交通大学附属儿童医院,上海市200040
出 处:《医学分子生物学杂志》2013年第3期172-176,共5页Journal of Medical Molecular Biology
基 金:上海市“科技创新行动计划”重大科技攻关项目(No.11DZ195030)
摘 要:长链脂肪酸β-氧化是动物获得能量的主要途径,长链脂酰-CoA脱氢酶(LCAD)是长链脂肪酸β-氧化起始步骤的催化酶。其调控机制主要包括表达调控和活性调节。LCAD由acadl基因编码,该基因的启动子区内存在多个起重要调控作用的顺式作用元件。由配体激活的过氧化物酶体增殖物激活受体(PPARs)与维甲酸X受体(RXR)形成异源二聚体,在辅助激活物的参与下形成转录调控复合物,结合在应答元件上调控LCAD的组织特异性和发育阶段特异性表达。此外,LCAD的酶活性可受去乙酰化酶SIRT3的调节,即通过使LCAD的K42脱乙酰化来提高其活性。机体对LCAD的精确调控使长链脂肪酸的代谢能够有序地进行,从而满足机体的正常生理功能需求。The long chain fatty acidβ-oxidation is a major pathway for animals to obtain energy. Long chain acyl-CoA dehydrogenase (LCAD) , encoded by acadl gene, is one of the enzyme responsible for the first step of long-chain fatty acid B-oxidation. Regulations of its expression and activity are two important mechanism involved in its regulatory process. There are a number of cis-elements located in the promoter of acadl gene. The peroxisome proliferator-activated receptors (PPARs) are activated by the ligand and combined with the retinoid X receptor (RXR) to form the heterodimer, which then binds to the responsive element of acadl. Tissue-specific and developmental stage-specific expression of LCAD is controlled by these transcriptional complexes. In addition, the activity of LCAD is regulated by SIRT3, an important deacetylase, through lysine (K42) deacetylation. All in all, the metabolism of long-chain fatty acids is carried out in orderly manner through the precise regulation of LCAD, which will help meet the demand of normal physiological function
关 键 词:长链脂酰-CoA脱氢酶 表达调控 活性调节
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