The role of propofol hydroxyl group in 5-lipoxygenase recognition.

The role of propofol hydroxyl group in 5-lipoxygenase recognition.
Biochem Biophys Res Commun. 2020 Mar 11;:
Authors: Yuki K, Bu W, Eckenhoff RG, Yokomizo T, Okuno T
Abstract
Propofol is a clinically important intravenous anesthetic. We previously reported that it directly inhibited 5-lipoxygenase (5-LOX), a key enzyme for leukotriene biosynthesis. Because the hydroxyl group in propofol (propofol 1-hydroxyl) is critical for its anesthetic effect, we examined if its presence would be inevitable for 5-lipoxygenase recognition. Fropofol is developed by substituting the hydroxy group in propofol with fluorine. We found that propofol 1-hydroxyl was important for 5-lipoxygenase recognition, but it was not absolutely necessary. Azi-fropofol bound to 5-LOX at one of the two propofol binding sites of 5-LOX (pocket around Phe-187), suggesting that propofol 1-hydroxyl is important for 5-LOX inhibition at the other propofol binding site (pocket around Val-431). Interestingly, 5-hydroperoxyeicosatetraenoic acid (5-HpETE) production was significantly increased by stimulation with calcium ionophore A23187 in HEK293 cells expressing 5-LOX, suggesting that the fropofol binding site is important for the conversion from 5-HpETE to leukotriene A4. We also indicated that propofol 1-hydroxyl might have contributed to interaction with wider targets among our body.
PMID: 32171526 [PubMed - as supplied by publisher]

Source: Biochemical and Biophysical Research communications - March 10, 2020 Category: Biochemistry Authors: Yuki K, Bu W, Eckenhoff RG, Yokomizo T, Okuno T Tags: Biochem Biophys Res Commun Source Type: research