Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with dual functions in the testis

Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with dual functions in the testis
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DOI:
10.1194/jlr.m800468-jlr200
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发表时间:
2009-05-01
影响因子:
6.5
通讯作者:
Shimizu, Takao
Shimizu, Takao
中科院分区:
生物学2区
文献类型:
--
作者:
Yuki, Koichi;Shindou, Hideo;Shimizu, Takao

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甘油磷脂是细胞膜的结构和功能成分,也是各种脂质介质的前体。使用酰基辅酶a作为供体,甘油磷脂通过新生途径(Kennedy途径)形成,并在重塑途径(Lands循环)中修饰。从1-酰基甘油-3-磷酸o -酰基转移酶(AGPAT)家族中发现了多种酰基转移酶,包括两种溶血磷脂酸酰基转移酶(LPAATs)。该家族的蛋白质含有酰基转移酶基序,但其生化特性和生理作用尚不完全清楚。在这里,我们证明了小鼠LPAAT3,以前被称为小鼠AGPAT3,具有很强的LPAAT活性和适度的溶磷脂酰肌醇酰基转移酶活性,并且明显倾向于花生四烯酰基辅酶a作为供体。该酶在睾丸中高度表达,其中倾向于1-硬脂酰-2-花生四烯酰基磷脂酸作为底物的cdp -二酰基甘油合成酶1也高度表达。由于1-硬脂酰-2-花生四烯醇是磷脂酰肌醇的主要成分,小鼠LPAAT3可能在新生和重塑途径中发挥作用,并有助于睾丸中1-硬脂酰-2-花生四烯醇-磷脂酰肌醇的有效生物生成。此外,这种酶在睾丸中的表达以年龄依赖性的方式显著增加,β -雌二醇可能是这种酶诱导的重要调节剂。我们的研究结果确定这种酰基转移酶是睾丸中产生磷脂酰肌醇的另一种重要酶。——yuki, K., H. Shindou, D. Hishikawa, T. Shimizu小鼠溶血磷脂酸酰基转移酶3的特性:一种在睾丸中具有双重功能的酶。[j] .油脂杂志。2009。: 860 - 869。
Glycerophospholipids are structural and functional components of cellular membranes as well as precursors of various lipid mediators. Using acyl-CoAs as donors, glycerophospholipids are formed by the de novo pathway (Kennedy pathway) and modified in the remodeling pathway (Lands' cycle). Various acyltransferases, including two lysophosphatidic acid acyltransferases (LPAATs), have been discovered from a 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family. Proteins of this family contain putative acyltransferase motifs, but their biochemical properties and physiological roles are not completely understood. Here, we demonstrated that mouse LPAAT3, previously known as mouse AGPAT3, possesses strong LPAAT activity and modest lysophosphatidylinositol acyltransferase activity with a clear preference for arachidonoyl-CoA as a donor. This enzyme is highly expressed in the testis, where CDP-diacylglycerol synthase 1 preferring 1-stearoyl-2-arachidonoyl-phosphatidic acid as a substrate is also highly expressed. Since 1-stearoyl-2-arachidonoyl species are the main components of phosphatidylinositol, mouse LPAAT3 may function in both the de novo and remodeling pathways and contribute to effective biogenesis of 1-stearoyl-2-arachidonoyl-phosphatidylinositol in the testis. Additionally, the expression of this enzyme in the testis increases significantly in an age-dependent manner, and beta-estradiol may be an important regulator of this enzyme's induction. jlr Our findings identify this acyltransferase as an alternative important enzyme to produce phosphatidylinositol in the testis.-Yuki, K., H. Shindou, D. Hishikawa, and T. Shimizu. Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with dual functions in the testis. J. Lipid Res. 2009. 50: 860-869.