title: Effect of endocannabinoids on soybean lipoxygenase-1 activity.
abstract: Endocannabinoids appear to be involved in a variety of physiological processes. Lipoxygenase activity has been known to be affected by unsaturated fatty acids or phenolic compounds. In this study, we examined whether endocannabinoids containing both N-acyl group and phenolic group can affect the activity of soybean lipoxygenase (LOX)-1, similar to mammalian 15-lipoxygenase in physicochemical properties. First, N-arachidonoyl dopamine and N-oleoyl dopamine were found to inhibit soybean LOX-1-catalyzed oxygenation of linoleic acid in a non-competitive manner with a Ki value of 3.7 μM and 6.2 μM, respectively. Meanwhile, other endocannabinoids failed to show a remarkable inhibition of soybean LOX-1. Separately, N-arachidonoyl dopamine and N-arachidonoyl serotonin were observed to inactivate soybean LOX-1 with Kin value of 27 μM and 24 μM, respectively, and k3 value of 0.12 min(-1) and 0.35 min(-1), respectively. Furthermore, such an inactivation was enhanced by ascorbic acid, but suppressed by 13(S)-hydroperoxy-9,11-octadecadienoic acid. Taken together, it is proposed that endocannabinoids containing polyunsaturated acyl moiety and phenolic group may be efficient for the inhibition as well as inactivation of 15-lipoxygenase.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Minh Duc
authors.initials: MD
authors.lastname: Nguyen
authors.forename: Dang Hung
authors.initials: DH
authors.lastname: Nguyen
authors.forename: Jae-Myung
authors.initials: JM
authors.lastname: Yoo
authors.forename: Pyung-Keun
authors.initials: PK
authors.lastname: Myung
authors.forename: Mee Ree
authors.initials: MR
authors.lastname: Kim
authors.forename: Dai-Eun
authors.initials: DE
authors.lastname: Sok
mesh_terms: D055162:Biocatalysis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D015394:Molecular Structure; D013025:Glycine max / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D063388:Endocannabinoids; D004791:Enzyme Inhibitors; C101084:lipoxygenase L-1; D008084:Lipoxygenase
keywords: 13(S)-hydroperoxyoctadecadienoic acid; 13-HpODE; 15(S)-HpETE; 15(S)-hydroperoxyeicosatatraenoic acid; E(ox); E(red); Endocannabinoids; Inactivation; Inhibition; LOX; N-acyl dopamine; N-arachidonoyl dopamine; N-arachidonoyl glycine; N-arachidonoyl serine; N-arachidonoyl serotonin; N-arachidonoyl taurine; N-oleoyl dopamine; N-palmitoyl dopamine; NA-5HT; NA-DA; NA-Gly; NA-Ser; NA-Tau; NO-DA; NP-DA; Soybean lipoxygenase-1; active ferric enzyme form; inactive ferrous enzyme form; lipoxygenase