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专题综述系列:甘油脂质。二酰甘油酰基转移酶(DGAT)与三酰甘油生物合成

Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis.

作者信息

Yen Chi-Liang Eric, Stone Scot J, Koliwad Suneil, Harris Charles, Farese Robert V

机构信息

Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706, USA.

出版信息

J Lipid Res. 2008 Nov;49(11):2283-301. doi: 10.1194/jlr.R800018-JLR200. Epub 2008 Aug 29.

Abstract

Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases.

摘要

三酰甘油(甘油三酯)(TGs)是大多数生物体内代谢能量和脂肪酸的主要储存分子。然而,TGs的过度积累与人类疾病相关,如肥胖症、糖尿病和脂肪性肝炎。TGs生物合成的最后且唯一的关键步骤由酰基辅酶A:二酰甘油酰基转移酶(DGAT)催化。在过去十年中,编码两种DGAT酶,即DGAT1和DGAT2的基因已被鉴定出来,并且使用包括任一酶缺陷的小鼠在内的分子工具,已经揭示了它们的功能。尽管DGAT酶参与TG合成,但它们具有不同的蛋白质序列,并且在生化、细胞和生理功能方面存在差异。这两种酶都可用作疾病的治疗靶点。在此,我们综述关于DGAT酶的当前知识,重点关注自其基因克隆以来的新进展,包括在人类健康和疾病中的可能作用。

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