2-arachidonoylglycerol（2-AG）是一種內(nèi)源大麻素,，是調(diào)節(jié)著一系列生理過程的脂類信號分子,，在神經(jīng)保護方面具有重要的作用,。12月27日《化學與生物學》（Chemistry & Biology）的封面文章,，描述了一項關于2-AG內(nèi)源大麻素的最新研究,，它全面揭示了使2-AG降解的大腦酶類,。
內(nèi)源大麻素在體內(nèi)的含量由合成和降解過程控制,，因此參與這些過程的酶類與大麻素的信號調(diào)節(jié)作用密切相關,。但是人們對2-AG在體內(nèi)的水解過程仍知之甚少，此前研究表明,，單?；视王ッ福∕AGL）和某些未知的蛋白質可能參與體內(nèi)2-AG的水解過程。
最新研究中,，Blankman和同事以小鼠大腦為研究對象,，用功能蛋白質組學的方法對體內(nèi)參與2-AG水解的蛋白質做了全面分析，結果表明MAGL在2-AG水解過程中起主要作用,，另外兩種新發(fā)現(xiàn)的水解酶ABHD6和ABHD12也參與了這一過程,。
進一步研究發(fā)現(xiàn)水解2-AG的三種酶MAGL，ABHD6和ABHD12在細胞內(nèi)的分布方式不同,，這表明它們可能分別在神經(jīng)系統(tǒng)的不同細胞或細胞內(nèi)不同位置起作用,。
該研究提供了一個范例，即用功能蛋白質學的方法能夠綜合分析參與某一生理過程的蛋白質,。（科學網(wǎng) 穆宏平/編譯）
生物谷推薦原始出處：
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.
