Tillander Veronika, Alexson Stefan E H, Cohen David E
Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, 14186, Sweden.
Division of Gastroenterology and Hepatology, Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
Trends Endocrinol Metab. 2017 Jul;28(7):473-484. doi: 10.1016/j.tem.2017.03.001. Epub 2017 Apr 3.
The cellular uptake of free fatty acids (FFA) is followed by esterification to coenzyme A (CoA), generating fatty acyl-CoAs that are substrates for oxidation or incorporation into complex lipids. Acyl-CoA thioesterases (ACOTs) constitute a family of enzymes that hydrolyze fatty acyl-CoAs to form FFA and CoA. Although biochemically and biophysically well characterized, the metabolic functions of these enzymes remain incompletely understood. Existing evidence suggests regulatory roles in controlling rates of peroxisomal and mitochondrial fatty acyl-CoA oxidation, as well as in the subcellular trafficking of fatty acids. Emerging data implicate ACOTs in the pathogenesis of metabolic diseases, suggesting that better understanding their pathobiology could reveal unique targets in the management of obesity, diabetes, and nonalcoholic fatty liver disease.
游离脂肪酸（FFA）被细胞摄取后会与辅酶A（CoA）酯化，生成脂肪酰辅酶A，后者是氧化或并入复合脂质的底物。酰基辅酶A硫酯酶（ACOTs）构成一类酶，可将脂肪酰辅酶A水解形成FFA和CoA。尽管这些酶在生物化学和生物物理学方面已得到充分表征，但其代谢功能仍未完全了解。现有证据表明，它们在控制过氧化物酶体和线粒体脂肪酰辅酶A氧化速率以及脂肪酸的亚细胞转运中发挥调节作用。新出现的数据表明ACOTs与代谢性疾病的发病机制有关，这表明更好地了解它们的病理生物学可能会揭示肥胖、糖尿病和非酒精性脂肪性肝病管理中的独特靶点。
