一种内源大麻素的水解酶类研究

2-arachidonoylglycerol（2-AG）是一种内源大麻素，是调节着一系列生理过程的脂类信号分子，在神经保护方面具有重要的作用。12月27日《化学与生物学》（Chemistry  &  Biology）的封面文章，描述了一项关于2-AG内源大麻素的最新研究，它全面揭示了使2-AG降解的大脑酶类。  

内源大麻素在体内的含量由合成和降解过程控制，因此参与这些过程的酶类与大麻素的信号调节作用密切相关。但是人们对2-AG在体内的水解过程仍知之甚少，此前研究表明，单酰基甘油酯酶（MAGL）和某些未知的蛋白质可能参与体内2-AG的水解过程。  

最新研究中，Blankman和同事以小鼠大脑为研究对象，用功能蛋白质组学的方法对体内参与2-AG水解的蛋白质做了全面分析，结果表明MAGL在2-AG水解过程中起主要作用，另外两种新发现的水解酶ABHD6和ABHD12也参与了这一过程。  

进一步研究发现水解2-AG的三种酶MAGL，ABHD6和ABHD12在细胞内的分布方式不同，这表明它们可能分别在神经系统的不同细胞或细胞内不同位置起作用。  

该研究提供了一个范例，即用功能蛋白质学的方法能够综合分析参与某一生理过程的蛋白质。（科学网  穆宏平/编译）

生物谷推荐原始出处：

Chemistry  &  Biology, December, 2007: 14 (12)

A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol
Jacqueline L. Blankman, Gabriel M. Simon, and Benjamin F. Cravatt

On the cover: 2-arachidonoylglycerol (2-AG) is a lipid signaling molecule that modulates a wide variety of physiological processes through activation of cannabinoid receptors. 2-AG signaling in the nervous system is terminated by enzymatic degradation, but this process has yet to be completely characterized. In this issue, Blankman and colleagues (pp. 1347–1356) describe a functional proteomic strategy to comprehensively survey mammalian brain enzymes that hydrolyze 2-AG. Their results reveal that in addition to the known 2-AG hydrolase monoacylglycerol lipase, two previously uncharacterized enzymes, ABHD6 and ABHD12, make significant contributions to total brain 2-AG hydrolase activity. The cover image depicts a panel of brain enzymes (shown as general α/β-hydrolase fold structures) screened for 2-AG hydrolase activity, with an active enzyme that cleaves 2-AG to arachidonic acid and glycerol highlighted in red. While a human brain is shown on the cover, the study was performed on enzymes enriched from mouse brain. All identified mouse brain 2-AG hydrolases have high-sequence identity orthologs in humans. Background shows primary neurons in culture. Cover art by Gabriel M. Simon.