Arand_2016_Matters_1_

The endocannabinoid 2-arachidonyl glycerol (2-AG) is substantially hydrolysed by at least two enzymes, fatty acid amide hydrolase (FAAH) and monoarachidonyl glycerol lipase (MAGL), which thereby terminate its biological activity. In a recent report it has been claimed that microsomal epoxide hydrolase (mEH), hitherto known as a xenobiotic detoxifying enzyme, also rapidly catalyses the breakdown of 2-AG. However, the catalytic site architecture of mEH argues against an esterase activity. We therefore analysed the capacity of recombinant purified human, mouse and rat mEH to hydrolyse 2-AG. In contrast to the previous finding, we find only marginal 2-AG esterase activity (<= 50 nmol/mg protein/min) associated with the purified enzymes that was resistant to inhibition by the potent mechanism-based mEH inhibitor 1,1,1-trichloropropene 2,3-oxide (TCPO). Likewise, 2-AG hydrolysis in mouse liver microsomes was resistant to TCPO inhibition while being efficiently blocked by methyl arachidonyl fluorophosphonate (MAFP). MAFP, on the other hand, failed to inhibit epoxide hydrolase activity of both, purified mEH and mouse liver microsomes. We therefore conclude that mEHlacks any appreciable 2-AG hydrolase activity. https://www.sciencematters.io/articles/201605000008/info DOI: 10.19185/matters.201605000008