双基酸盐通过基迁移的异构化
Akira Abe1, Vania Hinkovska-Galcheva1, Rakesh Verma1
1Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
双单糖酸盐 (BMPs) 可以从S,S-2,2'') 变异为S,S-3,3'') 形式,这些形式被 lysosomal phospholipase A2 (LPLA2) 优先降解. 这种异体化是由蛋白质和金属离子促进的,并在细胞中发生化后.
科学领域:
- 脂质生物化学 脂质生物化学
- 细胞生物学 细胞生物学
- 酶学 是一种酶学.
背景情况:
- 双单糖酸盐 (BMP) 是一种酸性脂质,存在于晚期内分体和溶解体中.
- lysosomal phospholipase A2 (LPLA2) 催化BMPs,对不同的BMP异构体表现出不同的基质特异性.
- S,S-(2,2'-diC18:1) -BMP被认为是主要的生物学相关异构体,而S,S-(3,3'-diC18:1) -BMP是一个更好的LPLA2基质.
研究的目的:
- 研究S,S-(2,2'-diC18:1) -BMP到S,S-(3,3'-diC18:1) -BMP的体外和细胞异构.
- 确定促进这种BMP异构化的因素和条件.
- 确定BMP异构化在细胞区间中的生物相关性.
主要方法:
- 薄层染色学用于区分BMP异构体.
- 化含有S,S-(2,2'-diC18:1) -BMP的脂质体,在不同的pH值下,在白蛋白的存在下.
- 用sn-1,3特异性脂酶对异构化产品的处理.
- 在RAW 264.7细胞中分析BMP水平,这些细胞被用黄素或NH4Cl处理.
主要成果:
- 在中性条件下,牛血清白蛋白促进了时间和度依赖的S,S-(2,2'-diC18:1) -BMP到S,S-(3,3'-diC18:1) -BMP的同质化.
- 异构化通过一个中间体进行,S,S-(2,3'-diC18:1) -BMP.
- 蛋白质 (HSP70,人血清白蛋白) 和金属离子 (Fe3+,Zn2+) 作为异构化的辅助因子.
- 细胞化 (chloroquine,NH4Cl治疗) 增加了对脂酶敏感的BMPs的水平,表明细胞中的异构.
结论:
- 在体外和细胞中,S,S-(2,2'-diC18:1) -BMP可以异构为S,S-(3,3'-diC18:1) -BMP.
- 这种S,S-(3,3'-diC18:1) -BMP异构体被LPLA2.2优先降解.
- 细胞区的pH影响BMP异构,这表明LPLA2活动的调节机制.
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